Last week, I had my 6th biopsy. I actually blogged (read: bitched) about it in a previous post. CNN version: when I went in for my routine mammogram, which turned into four separate boob squishes and an ultrasound, a spot showed up in my left boob – the one that had already developed two tumors (surgically removed) and had been irradiated. It was likely nothing, but since it was in the cancer boob, we went ahead and biopsied it.
It wasn’t nothing.
Bad grammar aside, once again (and near what was supposed to be my 2 year cancerversary), I got the call we all dread. It’s cancer. 6 mm invasive ductal carcinoma, ER+/PR+ (probably) HER2-, in the same breast that had been irradiated, and in the same body that’s been on estrogen blockers for nearly 2 years.
Once again, I’m numb, angry, scared, and filled with uncertainty. Invasive. How far has it spread? I should get a PET scan – what if it has metastasized? I’ll likely have a mastectomy at this point, one or both breasts, but what else? Will I need chemo? More radiation? A new drug cocktail?
Will I be alive next year? In two years? The statistics say yes, but what about five to ten years down the road?
Once again, I had to call family and friends with bad news, had to fall apart in my husband’s arms, had to tell my daughter. I still have to tell my son. I feel like I’ve failed. I’ve let them down. Should I have toughed it out with the aromatase inhibitors that made me so sore and achy that I could barely get out of my car, out of a chair, out of bed? Should I have gone for chemo in spite of my Oncotype DX results? Should I have just lopped off both breasts to begin with?
Rationally and objectively, no, I didn’t fail. Cancer is insidious, sly, and unpredictable. No one has a crystal ball. Based on the information we had at the time, breast conserving surgery made sense. I stand by that decision. I stand by my Oncotype DX results and decision to forgo chemo and opt for medically induced menopause and tamoxifen – because in order to live life, I needed to be able to get out of my car, out of chairs, and out of bed.
Here’s what I know: My odds are still good for survival. Losing one or both breasts is going to be painful, heartbreaking, and sad, but those are the cards I’ve been dealt and I will play them. I’ve been through this before, and years from now, I may go through it again, but I’m here now. I want to live. I want to watch my children grow and be there for them as they transition from incredible teens into amazing adults. I don’t want to miss a minute. I want more long days and loving nights with my husband. I want to laugh, travel, work, play, and not let cancer rob me of my life.
I don’t know how to get there yet, but I will get there. I will face what’s to come and I will keep fighting in the lab, as an advocate, and as a survivor. Cancer will not defeat my spirit. It will not rob me of joy for however long I may yet live. Strong, weak, confident, scared, sure, uncertain, and everything in between, I will face this.
I learned so many new things today at Patient Advocacy Orientation! My best days are when I’m learning new things. It’s one of the things I love best about being a scientist, and it’s a great foundation upon which to build for my new work as a Patient Advocate.
What exactly are advocates and what do they do? In terms of Research Advocacy Programs, advocates are disease survivors (cancer survivors in my case), caregivers, and members of the community who provide the patient perspective to researchers to help shape the nature and direction of cancer research and patient care. Their role is critical, as they serve as a voice for patients, helping investigators tailor their research with patients concerns in mind – not just in terms of outcomes and sound science, but also in terms patient comfort, respect for patient rights and dignity, and beneficence. This means making sure the goals of research are focused on and aligned with serving patient needs and improving outcomes and quality of life.
This seems pretty intuitive, and I believe most investigators are truly committed and passionate about doing research that will make a difference, be it developing new treatments, better diagnostic tools, reducing side effects of existing treatments, and improving survival and quality of life for patients. I certainly was and am. But most investigators don’t experience what patients do – except in cases like mine where researchers become patients and survivors. My experience certainly changed my perspective, which is why I want to share what I’ve learned with both the research and survivor communities.
That mission became more urgent for me today in the face of some jarring statistics. Tennessee and the surrounding regions have some of the highest cancer death rates in the United States.
Comparing the map above to the map below that shows new cancer cases diagnosed by state, incidence, the frequency with which cancer occurs, doesn’t fully explain higher death rates.
My heart sank when I saw these data, and really drove home my privilege. I am well-educated, have a high socioeconomic status, have access to insurance coverage and some of the best health care available in the United States, and I have inside information based on my work as a breast cancer researcher.
I’m lucky. Far too many of my fellow Tennesseans and Southerners are not. My Institution and Affiliated Cancer Center serve this region. I want to be a part of better serving patients in this region, which will be a HUGE focus of my advocacy work.
What will this work involve? One of the ways I think I can be of use is by helping recruit patients for clinical trials. According to what I learned today, many promising new drugs do not make it through Phase III clinical trial testing* due to failure to accrue enough patients to sufficiently test their effectiveness. That’s such a shame and missed opportunity. Of course, there are many barriers for patient participation in clinical trials – fear/lack of understanding; lack of access due to barriers to travel/transportation, unmet childcare needs, inability to take time off work, etc.; disparities that make minority populations reluctant to participate**. While I am not in a position to combat access to trials, I am in a position to serve as a liaison between patients and clinical researchers accruing patients for trials. I can help educate potential trial participants in the process, assure them of their rights (including the ability to stop participating at any time), alleviate fears through helping patients understand the benefits and how they might be helping a great number of future cancer patients. I am also working with African American advocates and other advocates of color to understand and be sensitive to those communities, their histories, and their needs.
Those needs are great, particularly in terms of breast cancer outcomes. African American women diagnosed with breast cancer have lower overall survival rates compared to white women. Finding out why is crucial for closing the gap. Increasing African American participation in clinical trials is a key part of that process.
For more on cancer disparities across ethnic groups, click here.
*I’ll cover clinical trials in more detail in a future post. Click here to learn more now. Phase III trials test drugs that have already been proven safe and promising in terms of effectiveness.
**African Americans remember the horrific abuses perpetrated by scientific investigators, including those in charge of Tuskegee Study of Syphilis – which resulted in hundreds of African Americans being denied treatment in order to study the long term effects of untreated syphilis
Warning: This post is full of swears. It’s been a total shit day.
Getting “normal” annual mammograms after breast cancer is nerve wracking. I get that. Literally. Today was my second routine mammogram after completing surgical and radiation treatments. What (I’d hoped) would be an hour long visit followed by an, “All clear! Go, and live happy,” turned into a 3 1/2 hour long ordeal that consisted of FOUR FUCKING IMAGING sessions, an ultrasound, and scheduling another biopsy.
This is fucking bullshit.
For those of you who’ve been there, done that, bought the T-shirt (that reads, “Of Course They’re Fake – The Real Ones Tried to Kill Me”), you get it. I’ve had several survivors in my circle offer support, well-wishes, and cat memes, and I’m grateful. For those of you who haven’t been there (and I hope you never are), let me give you some background. At the time of this blog post I’ve had:
Six biopsies (last time was a charm with the Big C)
Two lumpectomies (one to remove a benign papilloma and the other to remove cancer – followed by oncoplastic reconstruction involving a reduction and lift)
Implantation of TWO Savi Scout devices to mark my tumors (this was mammography assisted, meaning I was in fucking compression while two GINORMOUS needles the size of small screw drivers were stuck into my left boob and I actually saw the tip of one come out the other side)
Twenty-eight rounds of radiation on my left boob – crispy bacon, anyone?
And a partridge in a pear treeeeeeee!
You’d think that would be enough. Seriously. But, alas, not for me. Whenever I go in for routine checks, I get the extra imaging, the call backs, the ultrasounds, and the biopsies. My breast are pincushions. It’s not fun.
Today’s visit started out well enough. I went into the room with my lovely robe, wiped off the deodorant I’d put on (because I forgot that I wasn’t supposed to use any), flopped out one boob, then the other, let the nice nurse get to second base while positioning my boobs, had my (first) mammogram scans and returned to the waiting room. Aside from being a bit sore (the left boob, cancer boob, is harder than the right thanks to radiation and it’s pretty uncomfortable in the old squeezy squeezy machine), I was content. I texted the lab to tell them I hoped I’d be in soon and then enjoyed some Facebook and Twitter time while waiting. I also had in-room entertainment in the form of a brash and bawdy lady who was Skyping – loudly – and having the kind of inappropriate conversation that you kind of want to film because it’s disturbingly awesome and no one will believe you unless you record it. All in all, not too shabby.
Then, they called me back. Just need a few more images, they told me. Nothing to be concerned about. I groaned, but was still okay. Considering my normal experiences with mammograms, this was a drop in the boob bucket. I got squished, got sore, and was escorted back to the waiting room filled with other women in those high fashion robes you get when you have to get your boobies squished. My entertainment was gone, and I missed her terribly, but I was slightly more concerned with the passage of time.
I mean, I did have work to do.
They called me back again. This time, the nurse (BTW, they’re all wonderful and I don’t fault them for any of this) explained that they’d found a spot. It was of concern because they hadn’t seen it on my previous post-treatment scans. They hadn’t seen it, because apparently this time the nurse was so good that she got images closer to the chest wall and they were seeing new areas for the first time. On the one hand, go nurse! Great technique!
On the other hand, WTF is the spot? Is it something I should worry about? We don’t know how old/new it is because we haven’t seen it before. Seriously, I’m two years out. I shouldn’t have a recurrence.
They needed another set of scans to make sure it was real, especially since they’d seen it only in one image/plane. So, for the third time, back in the boob vise for a trip to fuck that hurts land.
I go back to the waiting room. And…I’m called back for – I shit you not – ANOTHER round of images. This time they let me stay in the room with the owie machine while I wait for the radiologist to have a peek. Shortly thereafter, they tell me, as I predicted by this point, it was ultrasound time!
I’ve had plenty of ultrasounds.
As is my standard practice, I asked if I could see the screen, explaining that I’m a breast cancer researcher. Yeah, I got breast cancer, too, the irony isn’t lost on me. Yes, I’ve become more passionate about my research and am getting into advocacy, too. Sure, I’d love to see the mammogram image of the spot in question. Interesting (i.e. I have no idea if what I’m seeing is bad or not – then again, neither does anyone else or I wouldn’t be here).
I flopped out my left boob, the one I’d called a pain in my ass during my 4th time in the booby squeeze machine (and made the nurse giggle snort), put my left hand over my head, got the ultrasound goo smeared over my bad boob, and then the nurse commenced with the scavenger hunt via wand. And she wanded. And she wanded. And she wanded.
My arm was getting a little numb, and I was a bit concerned that she wasn’t taking pictures, but I just chilled. Then, she told me she wasn’t sure anything she was seeing matched the spot on the mammogram. So she grabbed the radiologist, who came in, goo-ed me up, and wanded. And wanded. And wanded.
The radiologist laid it out for me. They’d seen this spot, which was uniform in shape, an oval, and was most likely nothing to be concerned about – fat necrosis, an artefact of scarring, or a benign lesion. Given that it was in my bad cancer boob, she recommended a biopsy. And since they couldn’t find it by ultrasound, I would need a mammogram guided biopsy.
That’s exactly as sucktastic as it sounds. I will be put in (terribly uncomfortable) mammogram compression and stay there while someone jabs a fucking biopsy needle into my boob. Yes, I’ll have lidocaine, but that’s not going to help with the squeezy squeezy or the HORROR!
And, while I wait 9 days for the biopsy and another 5-7 days for the results, I’ll be stressed out. This is the reality for survivors. We’re ALWAYS nervous with scans, and it’s compounded when extra examinations are needed. It’s terrifying. Yes, rationally I understand that the odds of finding another tumor are extremely low, but the fear is visceral and always there. I’m worried it always will be. Most days, I’m upbeat and snarkily positive, but not today.
Some days, the best you can do is just hope for better tomorrow.
Essential oils. They’re EVERYWHERE! Articles and posts touting their alleged benefits are all over social media, some news media, and the Internet. A Google search I performed today yielded 1.7 billion results. 1.7 BILLION! Yup, there’s a LOT of buzz about the wonders and medicinal benefits of essential oils.
And almost all of it 100% certified Grade A Bullshit.
This post is dedicated to debunking one of my least favorite bullshit woo woo scams (second only to homeopathy). And I will do so with the power of science and snark, because that’s just who I am as a person.
So what are essential oils? They are oils purified from plants and carry the aroma of the source from which they are extracted. Their name comes from the fact that they are thought to contain the essence of their source, and they smell pretty good thanks to terpenoids, aromatic organic compounds produced by plants that often function as chemical protection against herbivores, insects, and microbes. They also serve as attractants for pollinators, seed dispersers, and in mediating plant–plant and plant–microbe communication. Humans enjoy them because they smell and in some cases taste really good. Sadly, allergies prevent me from enjoying the florals, but I enjoy herbals and fruit oils in a wide array of products – cosmetics, soaps, perfumes, lotions, bath products, and many food items. They’re just nice.
But do they have any medicinal value? What about medicinal value when it comes to cancer? Part of the issue with answering this question involves the (lack of) regulation when it comes to production and testing. The concentration of active chemicals in extracts can vary widely from plant to plant, which parts are processed (different concentrations in leaves, flowers, stems, and roots), which season the plants are harvested, which strains are sourced, etc. Without consistent batches subjected to quality control to assure consistent concentrations of active chemical components (like terpenoids), and without rigorous, scientific studies, we can only rely on anecdotal evidence and (often misleading) claims from suppliers. Some efforts are being made by the WHO for quality and safety evaluation of herbal products, including chemical fingerprint analysis*. Much like vitamins and supplements, which are not subject to the same rigorous FDA standards for safety and efficacy (how well it works) as drugs, essential oils fall under the category of “safe for their intended use,” which does not involve use as medical treatments. They’re considered safe until proven otherwise, a MUCH lower standard than FDA approved drugs.
More importantly, they are (by fairly low standards) rated for safety, but not for EFFICACY. That would require clinical trials and rigorous testing.
Should we be researching them? Sure! Some pre-clinical studies involving cultured cells (cells grow in a petri dish under laboratory conditions) and animal (primarily mouse) models have been published. A systematic review of the literature from 2014 to 2019 identified 79 studies that fit inclusion criteria – including studies investigating essential oils with anti-microbial and immunomodulatory (affects the host immune response) properties, nutrition studies, studies with controls and proper statistical analyses. Of those studies, many documented the anti-microbial (bacteria fighting) and anti-fungal (fungus fighting) properties, antioxidant properties that may help slow food spoilage, and anti-inflammatory properties in laboratory and agriculture models. And, in some preclinical studies, high doses of essential oils can kill cancer cells in culture in a laboratory setting. Does that mean they’ll do the same thing in humans? Not necessarily. See my post on turmeric.
Just for perspective, it’s pretty easy to kill cancer cells in culture in a laboratory setting. I once killed a dish by accidentally leaving the cells in phosphate buffered saline instead of growth media. Yes, salt water can kill cancer cells in culture. So can many drugs, but the majority of compounds with anti-cancer activity in cultured cancer cells and mouse models are not effective in human clinical trials. So, the jury is out on whether or not the active ingredients essential oils can help treat cancer. And inhaling the pleasing aromas produced by essential oils may effect mood, but it doesn’t do anything to thwart cancer growth, survival, or invasion.
These observations definitely warrant more laboratory investigation, but as of this post, there is no evidence that essential oils fights cancer when inhaled or ingested or delivered in any other way into the human body. Advertisements by scammers like the ones listed below are lies:
These are some of the top hits under a Google search for “treating cancer with essential oils.” As is my standard policy, I will not share links for woo woo. The misinformation and outright lies are not only infuriating, they can prove deadly for patients who skip standard therapies in favor of alternative “therapies.” The stats are heartbreaking. In a Yale School of Medicine study (link to original publication here*), “patients who used alternative medicine in place of standard evidence-based medicine had a death rate 2.5 times higher than patients who received standard evidenced-based therapies.”
Women with non-metastatic breast cancer who opted for alternative “medicine” were ~ 6 times more likely to die within 5 1/2 years compared to women who received standard of care therapy. This is a small study – 281 patients – and captures data from patients who disclosed their decision to follow alternatives versus standard of care. It doesn’t include patients who do not disclose or discuss this with their health care providers, so the numbers could actually be higher.
For more information on aromatherapy – separating fact from fiction – click here. Check out this article, too. Bottom line: much like cannabis, essential oils may offer relief from the side effects of standard of care treatments, but they cannot cure cancer nor should they be used as a substitute for standard of care. Complimentary alternative medicine is fine, as it compliments proven therapies, but not on their own.
*Access to this article is limited by a paywall. If you want to read it for yourself, hit me up and I’ll send the PDF.
Yesterday, I wrote a post about scientific fact checkers and how scientists interact with them, using Dr. David Sabatini as an example. I did NOT expect the attention it garnered, but I do hope that Dr. Sabatini (if he read it) took it in the spirit in which it was intended. Like I noted in the original post, I’ve been following and admiring his work on mTOR for years. Thank in part to his efforts, mTOR inhibitors are in the clinic and are helping cancer patients fight their disease.
As a scientist, I find that very intellectually stimulating and gratifying. As a cancer survivor, I’m eternally grateful. Should my disease recur, torkinibs may be a part of my treatment plan, or perhaps third or fourth generation inhibitors. There are more options now thanks to the efforts of laboratory and clinical investigators around the world, and that gives us all so much hope!
At the end of the previous post, I noted that I, too, had been flagged on PubPeer for an error in a 2012 publication. What happened? In figure 4C, we inadvertently duplicated photomicrographs in the top panels:
Yup – the sharp-eyed PubPeer reviewer caught what the graduate student, collaborators, myself, my co-investigator, peer reviewers, and the journal production editors missed. The “Parental” and “Vector” images are identical. Not good. Now, this is a relatively minor error, but if left alone, it could lead to the perception that our laboratory group is sloppy and not as rigorous as we should be. In science, like many other fields, reputation is everything.
How does this happen? It’s a product of long hours poring over data, trying to select the best representations of experimental results, building figures and revising them…and revising them…and switching out panels and photos until the student or postdoc putting together the figures eyes are crossing. Many of them are sleep deprived, overloaded, and after a while, really numb to looking at the same data over and over again. Is that an excuse? No, it’s a reason, which is why study PIs, collaborators, reviewers, and the journal have a responsibility to double, triple, and quadruple check our papers before they’re sent out into the cyberverse for other scientists to read.
I take my part of the responsibility for this one. At the time, I was a Research Assistant Professor. While not on tenure-track, I was quite senior in the laboratory and had a duty to co-mentor and support the graduate students and fellows in the lab. My name was on the paper. I missed this and dropped the ball. That’s on me.
Fortunately, thanks to PubPeer, I have the opportunity to fix it!
After sorting through electronic files (thank GOODNESS our former lab members were organized), I was able to locate original images and generate correct (distinct) panels for Parental and Vector controls:
I contacted PLoS One today to request a correction. They may not re-issue the paper due to time and cost constraints, but I do hope they’ll add the corrected figure panels to an addendum. I’ll report back on this once I hear from them.
Bottom line: We ALL make mistakes from time to time. Yet, our culture discourages us from owning those mistakes, as if they’re a mark of shame or weakness. Certainly admitting mistakes has become uncomfortable and taboo. That is something that needs to change. Owning mistakes and fixing them are signs of integrity. When I’m entering into new collaborations, I pay attention to how my potential co-investigators and their team handle mistakes. Admission and ownership of mistakes and efforts to correct them are signs that new collaborators are trustworthy, rigorous, and have integrity, essential qualities in modern science. Very few scientific studies are performed by a single laboratory/person in that laboratory. Shared labor is the norm, so trust is key.
I WANT to be known as trustworthy, as someone with integrity whose work can be trusted and reproduced. As someone who recently withdrew a submitted manuscript when we (to our horror) found out that many of the data weren’t reproducible, I’ve become more vigilant. And I’m a better scientist for it. Science is better for vigilance. And that’s a good thing.
In the age of the Internet, trolls and trollish behaviors have multiplied exponentially. Science is not immune. Many of us were late coming to social media, but more and more laboratories, institutions, programs, scientific organizations, conferences, professional organizations, and journals are engaging in Twitter and other outlets. Overall, this is a great thing! It is so satisfying to peruse science Twitter and catch up on all of the latest findings, hot new studies and publications, and enjoy a community of peers that extends beyond the halls of individual institutions.
But OF COURSE there are trolls and trollish folks in the Twitterverse. Smart people aren’t immune to this. It’s human nature. Not our best quality as a species, but it’s there nonetheless and it extends to people across professions, educational backgrounds, political and religious ideologies…you get the idea.
No matter where you go, there’s always one (or more) assholes. That’s a fact of life, like death, taxes, and motherfucking reviewer number two.
A positive side-effect of the Internet Age is the rise of transparency and fact-checking. This is important in every field (side-eyes the news media), but especially in science. Scientists pore over the literature and build upon previous studies to move the field forward. If a study contains errors, inconsistencies, or (in the worst cases), fabricated or altered data, it undermines the integrity of the field and the scientific endeavor. That’s why sites like PubPeer work to spot inconsistencies in published scientific literature. Now, no one likes to have their mistakes posted in big bold font on the Internet, but setting aside ego and emotion, it’s actually a GOOD thing! It helps us be vigilant about our work and the work of our colleagues who contribute data to shared publications, it allows the authors of the studies in question to go back and examine the data and correct mistakes in collaboration with the journal in question. It makes science more rigorous. All good things.
The scientist in question decides to get his or her TROLL on!
When a mistake is pointed out on PubPeer, there are basically two ways to handle it. #1 – Thank the fact checkers for finding the error, dig through the data and fix the mistake, contact the journal in which the mistake was published and (if possible) update the data presented or add a note with the updated data as an addendum, and promise to be more rigorous in the future. This is the best way to handle it. It preserves your integrity as a scientist (and the integrity of the scientific process), it shows your commitment to ethics and responsible conduct of research, and it shows that you value your reputation and quality of your work enough to protect it. Basically, it makes you look good, honest, trustworthy – all qualities you want to have as a human being and a scientist.
Then, there’s the second way to handle it…#2 – Insult the PubPeer fact checker (petty, failed scientists), block “steaming turd,” (grudgingly) contact the journal to see what you should do. See this post from For Better Science for the run down. The first two items are childish, unnecessary, and, well, trollish. Mistakes happen, even to the great and mighty Dr. David Sabatini (whose work I actually follow and admire, since I’m working on mTOR signaling in breast cancer in my own lab). He’s a leader in the field, and he could have used this as an opportunity to set a great example for his peers and colleagues by handling this situation, which happens to plenty of scientists, with grace, dignity, and integrity. Someone with his reputation and in his position has a great deal of influence and sets the tone for scientists at all levels.
This is not a great tone. This is not a good look. I’m 95% certain that, had he not gone on Twitter and got his troll on, no one would be talking about the errors that have been found in multiple papers. He could have quietly fixed them and moved on.
Instead, EVERYONE is talking about this. This isn’t the kind of publicity you want as a scientist. Here are some Twitter replies:
There are even more replies to the first post, some showing sympathy and support – while gently pointing out the importance of the work PubPeer is doing – others (who tend to get blocked) calling out Dr. Sabatini on the insults borne of ego. It didn’t have to go down like this. It’s sad and unfortunate that it did. Hopefully, it will serve as an example of what NOT to do when confronted with evidence of error in published work.
For a GREAT example of what to do when confronted with evidence of mistakes in a publication, check out how Nobel Laureate Dr. Frances Arnold retracted a published study when she and her colleagues found the results were not reproducible missing data from a lab notebook. This is a fantastic example of integrity, honesty, and ethics.
*Note – you might be wondering if I’m just armchair quarterbacking, safe in the knowledge that I’m not the one being called out by PubPeer. I am not. In fact, when I joined PubPeer and did a search on my name, I found a post about an error in a 2012 PLoS One paper for which I was a co-author – we accidentally duplicated a photomicrograph. These things happen, but I’m GLAD the PubPeer fact checker spotted it so we have the opportunity to correct this. We are working on it NOW!
(And yes, I did thank the fact checker, because my mama raised me to have manners)
One of my favorite outreach activities is volunteering at public schools. Over the years, I’ve had the opportunity to speak to and work with elementary, middle, and high school students – doing everything from dry ice demonstrations, mini anatomy labs with fixed mouse organs, microscopy labs with tissue sections, and career talks. Most recently, I visited a local MNPS high school to talk about cancer biology (click here to see the slide show and an explanation).
It was AWESOME!
First of all, I was super impressed by how much these young people already knew! They’re studying cell biology and cell division right now, which worked well for my talk about how errors in DNA replication, mutations, and failed repair after damage leading to amplifications and deletions contribute to cancer. We used cell cycle regulation as an example, talking about oncogenes (drive cancer growth) and tumor suppressors (normal braking system for growth – lost in many cancers) that encode cell cycle regulators. They already knew much of the background, including how the cell cycle is controlled, the steps involved, and some of the proteins that regulate it. They also knew a lot about carcinogens (e.g. cigarette smoke, ultraviolet radiation from the sun, certain chemicals), treatments (chemotherapy and radiation), and certain types of cancer including breast, lung, and colon cancer.
Secondly, they were engaged and asked a LOT of questions. It made the presentation much more fun and interactive, and it gave me quite a bit to think about. There were, of course, questions I could not answer off the top of my head. But I promised the students I would look up answers to their questions and send the answers to their teacher. These are some of those questions:
1. What is the rarest form of cancer?
The latest statistics I could find from the American Cancer Society are from 2017. According to the data they gathered, the rarest cancers diagnosed in the adults (20+ years old) in the United States include cancers of the trachea, Kaposi sarcoma (this one is interesting because it led to the discovery of HIV – when more of these cancers cropped up in young gay men in the 1980s, it led investigators to start studying this population to identify the cause), lip, nose cavity and middle ear.
2. Can cancer in a transplanted organ spread to a new host?
This has actually happened! In 2018, it was reported that a 53 year old woman who died from a stroke and had no known medical conditions at the time of her death (including screens for cancer) had her organs transplanted into at least 5 recipients. The patient who received the heart died shortly after transplant from unrelated causes, but a year and a half later, the patient who received lungs from the donor became ill and was found to have breast cancer cells in her body with DNA that matched the original donor. She died shortly after. The patient who received the donor’s liver developed breast cancer in the transplanted organ in 2011, was treated, but died of a recurrence in 2014. The patient who received the donor’s left kidney developed and died from breast cancer in 2013 (six years after transplant), and the patient who received the donor’s right kidney was diagnosed with breast cancer in his kidney cells in 2011 – they were able to remove the tumor from the kidney, and after treatment the patient lived 10 years cancer free (at the time of reporting).
This phenomenon is very rare, however, and most of the time cancer in a potential donor can be detected by screening before organ harvest.
3.Do clams or reptiles get cancer?
Apparently, clams do get cancer. Even worse, for at least one type of cancer, the cancer cells from one clam can travel to another clam through water and grow in the new host. Yikes!
Cancers have been documented in reptiles, but they are much more under-studied than mammals and other animals. More research may be done to better study the link between cancer and metabolism, since metabolism is lower/slower in ectotherms (cold blooded creatures) than endotherms (warm blooded creatures).
Interestingly, elephants and naked mole rats rarely, if ever, get cancer, and ongoing studies into their physiology and genetics could help us figure out why and how we can use the knowledge to prevent cancer in humans.
4. Can babies be born with cancer?
It is rare, but it can happen. There have been reports of babies born with neuroblastoma, leukemia, and teratomas.
5. When did people start getting cancer?
(I actually knew part of the answer to this one, but it was fun to dig a little deeper)
The world’s oldest recorded case of cancer came from ancient Egypt in 1500 B.C., and it was recorded that there was no treatment for the cancer, only palliative treatment (relief of pain and suffering). Cancer has been with us much longer, though, given that bone cancer (osteosarcoma) has been detected in fossils from early hominids dated to 1.7 million years ago. Similar tumors have been found in fossils from dinosaurs and even from ancient turtles that lived 240 million years ago!
Got any questions for me? Send them! I’ll do my best to find the answers and more information. Knowledge is power! Hit me with your burning questions – the weirder the better!
If I had a quarter for every time someone told me they read that some discovery was the cure for cancer over the past twenty years, I could afford to take that trip to Tahiti I’ve been dreaming about. Science and the news media have an interesting relationship. On one hand, it’s always great to get coverage for advances in science. It keeps the public informed and engaged, which in turn means more interest and research dollars for laboratory and clinical investigation.
On the other hand, the news media gets a lot wrong, and that’s actually bad for keeping the public informed and for public perception and expectations, especially when it comes to complex diseases like cancer.
Take, for example, recent press coverage of a discovery related to tumor immunology – the study of how we can harness a patient’s own immune system to fight their cancer. It’s a hot topic. In fact, two leaders in the field, James Allison and Tasuku Honjo, were awarded the Nobel Prize for Physiology and Medicine in 2018 for their discovery of a new cancertherapy by inhibition of negative immune regulation, which led to the development of several drugs currently available to treat certain types of cancer. More recently, a paper published in Nature Immunology captured the attention of news outlets, leading to headlines like:
The first outlet, Science Alert, gets it right. The discovery is indeed remarkable, and the note about the ability to kill several cancer types in the laboratory is an accurate representation of what the study showed (my only issue with the headline is the clunky construction – discovery doesn’t kill anything – but that’s just me being nitpicky). The study tested activity of T-cells, part of the immune system that kills cells that have been infected by pathogens (bacteria and viruses) that can also be engineered to target cancer cells in cell culture (cells grown on a plastic dish in the laboratory) and in mouse models (mice engineered to make tumors or transplanted with tumors). This is an essential first step for the development of new therapies, but it is a far cry from being ready to use in patients, as the BBC News and Newsweek headlines might lead people to believe.
But can switching to these new T-cells save me 15% or more on car insurance?
I get why this happens. In the age of 24 hour news cycles, multiple media outlets (online, television, radio, and print), sensational headlines sell. The idea that a new discovery could treat all cancer (a far-fetched notion given that cancer is a collection of diseases that are unique and adaptable) sounds exciting. It captures public interest, especially in patient and survivor communities. But those headlines are misleading, and that’s a problem. While most of the public will forget the specifics, some will look at the next headline related to cancer and think, “Wait, didn’t they find something that’s going to cure cancer soon? What happened to that?” The false promises made by these headlines can give the public the idea that most of what cancer researchers are doing is a waste since the sensationalized discoveries didn’t live up to the hype.
So, let’s look beyond the headlines and delve into the study. What did the investigators do (experimental methods and models), what were the results (data), and what do the results tells us (interpretation)?
To begin, we need a basic understanding of how T-cells (one of many cell types in the immune system) function in fighting disease. They are part of the adaptive immune response – meaning they are selected to attack specific pathogens based on unique proteins and, as noted in the paper, metabolic by-products, produced by target cells.
Here’s how it works: when a cell becomes infected with a bacteria or virus, the infected cell takes some of the foreign proteins (antigens) from the bacteria or virus and displays it on the cell surface in combination with proteins (major histocompatibility complex [MHC] – also known as the human leukocyte antigen [HLA] system in humans] that communicate with immune cells. Surveillance cells like macrophages, which can “eat” infected cells, also do this, and these cells are known as professional antigen-presenting cells (APC). Helper T-cells in the vicinity that recognize the antigen communicate with B-cells, which make antibodies to attack cells that are infected and display the same antigen, and with Killer T-cells (cytotoxic), which bind to and destroy infected cells that express the same antigen. In order to bind to the antigen/MHC complex, T-cells like the killers use cell surface protein receptors (T-cell receptors [TCR]). This is how conventional T-cells function.
Now, on to breaking down the actual published study!
The new study focused on unconventional T-cells that do not recognize protein antigens bound to MHC on antigen-presenting cells. These specialized T-cells normally sense bacterial metabolic by-products bound to the evolutionarily conserved, monomorphic MHC class 1-related protein MR1 – a fancy way of saying that the MR1 cell surface receptor is similar across species (evolutionarily conserved) and come in one form (monomorphic). This types of T-cell was identified from an experimental screen used to identify tumor-educated (e.g. grown in response to tumor cells) T-cells that recognize and kill cancer cells in a petri dish in a non-MHC (MHC mismatched) manner. This is important, since MHC/HLA are some of the most variable proteins within and between people and therefore not easy to develop and exploit as a universal anti-cancer treatment. The T-cell clone identified, called MC.7.G5, was able to kill cells from different types of cancer (lung, melanoma, leukemia, colon, breast, prostate, bone and ovarian) with different MHC/HLA types in petri dishes without harming normal, healthy cells.
Using other molecular biology techniques, the investigators determined that the T-cells that can recognize and destroy cancer cells in a non-MHC-dependent manner. Rather, the cancer-killing T-cells had receptors (TCR) that bound to MR1 plus a cancer-specific cargo (antigen – possibly a non-protein antigen) that has not yet been identified.
To see if these T-cells kill cancer in a whole animal model system, the investigators transplanted human leukemia cells into mice that lacked a functional immune system along with MC.7.G5 T-cells. The mice that received the MC.7.G5 T-cells showed evidence of reduced leukemia cells relative to controls, and when they tested leukemia cells that did not express MR1, the anti-leukemia activity went away – this is an important control, because it shows that MR1 is, in fact, necessary for MC.7.G5 T-cell activity. Finally, the investigators purified T-cells from actual patients with stage IV (metastatic) melanoma, engineered the purified T-cells to express the same T-cell receptor as MC.7.G5 cells, and tested the ability of these engineered T-cells to kill melanoma cells in a petri dish. The cells engineered to express the MC.7.G5 TCR killed melanoma cells from patients with similar or dissimilar HLA, but not melanoma cells that didn’t express MR1.
So what does all of this mean?? The significance is that T-cell subtypes that may be present in most humans and similar in most humans can recognize and destroy a variety of different cancer cells in laboratory models. It is exciting because, if validated in more laboratory research models (and if these types of T-cells are observed in actual cancer patients, including those with better outcomes), it could give scientists and physicians a new therapeutic tool to use in the clinic.
Before that can happen, a LOT more work has to be done, including:
Figuring out what cancer-specific antigen MR1 binds to – this is super important, since the presence of whatever that antigen might be would have to be detected in actual cancer patients before trying out these new T-cells in clinical trials.
Long-term studies to see if the health of the animal is affected by exposure to T-cell therapy. One of the challenges with anti-tumor immune therapy is the risk that patients might develop an auto-immune disease (e.g. immune cells will recognize the patient’s own healthy cells and attack, like what happens in Type I diabetes and Rheumatoid Arthritis). Remember, cancer cells are normal cells gone rogue, and they may be similar enough to normal cells within the body to trigger an unwanted immune response.
Getting the T-cells to go to the tumor, infiltrate it, and kill enough tumor cells is also a challenge. It’s a challenge with all immune therapies. Tumors that normally have a lot of T-cells hanging around (“hot” tumors) generally respond better to existing immune activating drugs, but many tumors don’t have a lot of T-cells that infiltrate (“cold” tumors”). These new T-cells can only be effective if they can get to the tumor, and tumors often adapt to evade or repel immune cells.
Finally, just because something works in laboratory models, like cells in petri dishes or even laboratory mice, doesn’t mean it will work in humans. We’ve been successfully killing cancer in petri dishes and mice for decades, and the clinical trials graveyard is full of therapies that showed great promise in the laboratory only to fail in clinical trials – some of those cases may be due to trial design, especially in early trials where patients weren’t always screened for the target. But other cases are probably due to our inability to replicate human disease fully in models that are not as naturally complex. Most mouse models used in the laboratory are inbred (for more on the history behind that, follow this link – yes, I know it’s a Wikipedia link. Wiki isn’t always wrong.). This means we’re using clones in our experiments, and some of those are even more abnormal since they don’t have a functional immune system. The advantage is that we can get more consistent, reproducible results and also that we can get mice without an immune system to grow human tumor cells without rejecting them. The disadvantage is that humans, not being clones, vary widely in their physiologies and responses to therapy. And even when it comes to mouse tumors grown in mice with a working immune system, there are differences in how mouse and human immune systems work – actually, in my experience, laboratory mice are WAY more resilient and resistant to infections than people.
Take home message – look past the headline to the actual data.
It’s a lot of work and requires a fair amount of background knowledge to go to the primary literature and make sense of it, but often enough, the story below the headline can give you enough information to figure out what a study shows, what it doesn’t show, and how close the results are to making it to the clinic.
For example, the BBC News article states that “The findings, published in Nature Immunology, have not been tested in patients, but the researchers say they have “enormous potential”.” I’ll also give the author of this article props for explaining CAR-T cell technology – which is how the cancer-fighting T-cells may be engineered from patient T-cells if the study findings are translated to the clinic. But the headline? Totally misleading.
Same goes for Newsweek, which presents the full headline as: ‘ONE-SIZE-FITS-ALL’ CANCER TREATMENT COULD BE ON THE HORIZON AFTER SCIENTISTS DISCOVER NEW IMMUNE CELL BY ACCIDENT.” Not the accident part – scientists discover stuff by accident all the time, but the idea that this is “on the horizon” gives the impression that it’ll be going to the clinic very soon. Um…not likely. Still, within the article, the author notes, “In mice experiments and in lab dishes, the team showed that a new type of what are known as T-cells could detect a range of cancerous cells, while differentiating them from healthy cells.” That, in a nutshell, is what the investigators actually showed. Headline is still misleading, though.
Bottom line – look BEYOND the sensational headline. It’s purpose is to hook you and get you to click on and read the article (while being bombarded with ads). Dig into the actual article to find out what the new and exciting study shows.
Last week, I had the opportunity to speak with students in Freshman Biology classes at Overton High School here in Nashville. I’d given science demonstrations before—including fun with dry ice and a mouse organ scavenger hunt/anatomy lesson that was fun for everyone except one squeamish student. But I’d never spoken in detail about cancer biology and cancer research.
I’ve been saying (read: complaining) for YEARS about how scientists are terrible about speaking with the public. We talk to each other all the time at our institutions and at scientific conferences, but not enough of us reach out to our communities, and that’s a shame. First of all, we as scientists should be advocates for the scientific process and for the progress we’re making. Second, scientists are in a position to combat scammers, pseudoscience, and mis/disinformation by sharing our knowledge. Third, most of us are funded, at least in part, by the federal government. I’m funded by The National Institutes of Health (NIH) through The National Cancer Institute (NCI) – those agencies are funded by federal tax dollars. Since I’m paid by tax dollars, I personally feel an obligation to be able to explain what I do and why it is important to taxpayers in terms they can understand.
So, in my new role as a cancer researcher who has also survived cancer, I’m putting my time and effort where my big fat mouth is and getting out there to be an ambassador and advocate for cancer research! I occurred to me that the slides from my recent presentation for high school students would make a great addition to this blog. It covers how normal cells transform into malignant tumor cells at the molecular level.
The goal of this presentation is to provide a brief overview of how damage to DNA, the genetic code that is used to build proteins (the workhorses of a cell) can lead to uncontrolled cell growth and survival – both hallmarks of cancer. Damage to DNA and failure to properly repair that damage can lead to mutation (change in the code), amplification (more copies of a gene than normal), deletion (loss of DNA and the genes encoded). When changes in DNA occur in genes that regulate cell division, this can contribute to cancer. Uncontrolled cell growth is fundamental to cancer.
To understand how DNA damage leads to cancer, we first have to review what DNA actually does – The Central Dogma of Molecular Biology. I covered this in a previous post, but I’ll go over it again for the (vast majority of) people who don’t spend their days thinking about and doing molecular and cellular biology research. The more frequently you see information, the more likely you’ll be to remember it.
DNA is the blueprint that contains instructions for how to build every protein a cell needs for its normal function. Since, as we’ll see in the next few slides, DNA damage can cause huge problems for cells, DNA is protected in an organelle within the cell called the nucleus. It is only unwound from its double helix structure during (1) DNA replication when the cell makes extra copies before dividing, and (2) when tiny portions, genes, are transcribed (copied) into small units called RNA. RNA gets transported out of the nucleus where the code is translated to make proteins. Each sequence of three base pairs encodes a specific amino acid (building blocks of protein). Take home = DNA to RNA to protein. And DNA damage leads to problems with the proteins they encode.
So what do proteins do? The answer is pretty much everything a cell needs to function. Two specific classes of proteins, those involved in regulation and signaling, are the targets of mutations/amplifications/deletions that can lead to cancer. Regulation involves turning cellular processes, like cell division, on and off. Signaling involves proteins transmitting messages from outside the cell to the inside — including messages that tell the cell when to divide.
DNA can be damaged or altered by internal factors and external factors. Errors occur in replication (copying during cell division), and if they aren’t repaired properly, they can lead to mutations. Other things that can damage DNA include ultraviolet light (sunlight – skin cancer), chemicals (carcinogens) in cigarette smoke, and exposure to radiation. Base mismatches can lead to a change in the code. Single-stranded and double-stranded breaks can lead to amplification or deletion of essential genes in the cell division process. Damage to DNA in genes that encode DNA damage repair proteins are especially harmful, as failed repair leads to more mutations, amplifications, and deletions that accumulate and lead to cancer.
Mutations and DNA damage occur relatively infrequently. Most mutations are silent, meaning that they don’t affect the production or function of the protein the gene encodes, and it takes more than one mutation to transform a cell and make it cancerous.
The types of genes that drive cancer include oncogenes and tumor suppressors. In the cell division process, there are many on/off switches that tell the cell when to divide and when to stop the process of division. Oncogenes, which are amplified (more copies of the gene than normal made after DNA damage) or mutated to be super active, are the “go” signals, like a car’s accelerator. Tumor suppressors, which are deleted (genes are lost after DNA damage) or mutated to be non functional, are the “stop” signals, like a car’s brakes. A combination of amplified/mutated oncogenes plus deleted/mutated tumor suppressors transform a normal cell into a cancer cell that then divides uncontrollably, like a speeding car with the brake lines cut.
On/off switches in the cell cycle, the series of steps that a cell follows to divide and make two cells, have the potential to become oncogenes and tumor suppressors.
This slide shows an example of an oncogene and tumor suppressor in a signaling pathway that contributes to breast cancer. Cyclin-dependent kinases (CDK) are enzymes that tag other proteins with phosphates (P) groups, which serves as a signal for the tagged protein to perform its function. In the case of CDK4/6, its substrate RB (off switch for cell cycles) is tagged with phosphate, which marks it for destruction by the cell. When RB is destroyed, it releases its buddy E2F, freeing it to help the cell make more proteins required for cell division. CDK2/4 function is activated (on switch for cell cycle) by binding to its buddy cyclin D1, and is deactivated by its inhibitor p16. The gene encoding cyclin D1 is commonly amplified (more copies) in breast cancer, and the gene encoding RB is commonly mutated or deleted (gene lost or mutated to make a non functioning protein). Thus, cyclin D1 is an oncogene, and RB is a tumor suppressor.
That’s the overview, but this time I include specific examples. There are many other oncogene drivers and tumor suppressors that contribute to breast cancer and other cancers. I’ll cover some of those in future posts. Hope y’all enjoyed this Science Break! Shout out to Dr. Shannon Youngman and the students from Overton for hosting me and asking some great questions!
Like many actual scientists and rational human beings, I have issues with Gwyneth Paltrow’s activities as a “wellness guru” by way of her company, GOOP. Don’t get me wrong, she’s an incredible actress and supports some great philanthropic work, including the work of The American Cancer Society and The Breast Cancer Research Foundation. And I don’t have a big problem with her capitalizing on her fame and looks in the beauty industry. We all like to look and feel pretty.
But GOOP as a resource for health and wellness is another matter. From coffee enemas for “detox” (note – all you need for detox are a liver and functional kidneys), vaginal steaming (that’s a recipe for a rip-roaring yeast infection and severe burns), and jade eggs to stick up your vagina (not healthy – and don’t just take my word for it; Dr. Jen Gunter, OB/GYN and author of The Vagina Bible confirms what common sense would tell most women: nothing good can come from sticking rocks up your hoohah), this whole “wellness” thing is actually pretty freakin’ unhealthy. So much so, in fact, that a lawsuit cost the biz $145K (for baseless claims about the benefits of vagina eggs – really just a drop in the bucket for them) and now they include disclaimers about their whackadoodle health claims.
And…now she’s selling a candle that allegedly smells like her vagina. You can’t make this shit up. The candle is called “This Smells Like My Vagina.” It’s right there in the name. Now, I’m not going to unpack all of the patriarchal bullshit that goes along with how women’s bodies should look and smell – your vagina smells fine. Trust me. It smells like it’s supposed to. No one is marketing products to freshen up sweaty ballsacks, which tells you pretty much everything you need to know about sexist double standards when it comes to eau de genitals.
But aside from all of that, what does Gwyneth’s snatch-scented candle (allegedly) do? And, I have to ask, did she actually stick the candles into her snatch to infuse them with her feminine “energy” and alluring musk? Apparently, this candle actually smells like “a blend of geranium, citrusy bergamot, and cedar absolutes juxtaposed with Damask rose and ambrette seed [note – um, that’s not what vagina’s smell like] that puts us in mind of fantasy, seduction, and a sophisticated warmth.”
Well, at least she didn’t claim it cures cancer, so bonus.
This is the same woman who falsely claimed thatunderwire bras could cause breast cancer – they can’t and don’t. That shit really pisses me off. She’s not a trained healthcare provider, a scientist working in a laboratory (the GOOP “lab” show that’s coming to Netflix is NOT a lab and I’m probably going to rage post and Tweet about all of the false claims that will no doubt come out of that train wreck), and she has no expertise in this arena. So, my advice to Gwyneth Paltrow is this: stay in your fucking lane. You’re an actress, not a health expert.
Seriously, there’s nothing inherently wrong with a bit of…whimsy when it comes to lifestyle choices. If it feels good and it doesn’t hurt you, then, hey, you do you. The problem is that much of what overpriced celebrity brands like GOOP peddle actually CAN hurt you (remember that whole vaginal burn thing a few paragraphs back?). Worse, in this age of anti-intellectualism, where a large segment of the world population does not value or respect scientists and healthcare provider expertise, celebrities have become a go-to for “the answers” to all of your health woes. That’s a problem.
So what do we do? For starters, use common sense. If something sounds weird (even if it’s allegedly been practiced for centuries by ancient wise women in some place the seller is culturally appropriating for financial gain), it’s probably a scam. If your healthcare providers and people with actual degrees and expertise (e.g. SciBabe, Jen Gunter, Sana Goldberg – Dr. Oz totally does NOT count) advise against it, it’s probably a scam. If it’s a seemingly ordinary item (vagina scented candle) that costs a ridiculous amount of money ($75 – what the ACTUAL fuck), it’s probably a scam. Be smart, stay safe, and don’t be fooled!
Click here for some more hilariously/sad/ridiculous vagina trends from Ms. Paltrow . For SciBabe’s entertaining and informative take on Gwyneth Paltrow and GOOP, click here.