Three New Frontiers In Cancer Medicine
THE FUTURE OF MEDICINE WITH BEN STANGER
Browsing a bookstore in Harrisburg, PA, I happened across the newly released From One Cell – a Journey Into Life’s Origins and the Future of Medicine by Ben Stanger. With a title like that, I couldn’t help but pick it up, and when I scanned the pages I saw it not only told the wonderful story of the intricacies of cells and how they choose their identities and meld themselves into animals (us!) but combined this with a human history of the scientists behind the discoveries – my kind of book! So I bought it, and later, reading it in my hotel room, I checked out the author and discovered he was a professor of cancer research, and a professor of cell and developmental biology at UPenn — the very place where I was headed to conduct interviews on the future of medicine! So I asked if he’d make time to meet, and he graciously said yes.
MEETING BEN STANGER
Dr Ben Stanger is the Hanna Wise Professor in Cancer Research at the University of Pennsylvania Perelman School of Medicine. He’s also Director the Penn Pancreatic Cancer Research Center and a member of half a dozen other prestigious Institutes. What a guy! In addition to his many prestigious academic positions, he still practices AND makes time to write science for a popular audience. We met in his office, and since we are both passionate about good storytelling, I knew I would enjoy his company. In our half-hour conversation, we discussed From One Cell (if you have any interest in the cutting edge of medical science and where it is taking the future of healthcare, I thoroughly recommend it!) after which Ben shared his optimism for three new frontiers in cancer medicine: the advancement from liquid to solid tumors, the new ways we are attacking pancreatic cancers (including via mRNA cancer vaccines) and the latest work being undertaken in ‘cancer interception.’
Enjoy the podcast! And don’t forget to subscribe on Spotify or your favorite podcast platform to hear more from future-makers like Ben.
CHECK OUT THE PODCAST TRANSCRIPT →
FROM BLOOD CANCERS TO SOLID TUMORS
Anyone who has attended one of my Future of Medicine keynotes knows I often tell Emily Whitehead’s emotional and inspiring story (as the world’s first recipient of CAR T-cell therapy, which destroyed her acute lymphoblastic leukemia) as a ‘foundation story’ to discuss the future of cancer therapies, and how gene therapies more broadly are reshaping the future of medicine. The big new frontier here is switching from blood cancers like Emily’s to solid tumors (e.g. breast cancer, lung cancer, pancreatic cancer).
There are obvious ‘mobility’ advantages when targeting cancers in the blood, and blood cancers offer more consistent markers to target. With solid tumors, the cells are less accessible, and target antigen heterogeneity makes it tough for T cells to find and attack in all the right places.
Ben pointed to endogenous retroviruses, which can become activated by cancers, as a possible ‘tangential’ method for targeting cancers that the lab is working on. Talk about thinking outside the box! They are also working on overcoming the immunosuppressive nature of the tumor, the fact that it doesn't want the T-cells to get in there and kill the cancer cells.
A phenomenon called “T cell exhaustion” also gets in the way when attacking solid tumors. As explained in this UPenn article, this is “where the persistent antigen exposure from the solid mass of tumor cells wears out the T cells to the point that they aren’t able to mount an antitumor response. Engineering already exhausted T cells from patients for CAR T cell therapy results in a less effective product because the T cells don’t multiply enough or remember their task as well.” The article goes on to explain a strategy that could “make each T cell more potent, and replicate them to greater quantities, we expect T cell therapies to have a better shot at attacking solid tumors.”
For the science-oriented reader, this article in Frontiers chronicles many of the hurdles in targeting solid tumors, and the MANY different clinical trials currently underway in the world testing new methods to overcome them.
THE #2 DEADLIEST CANCER
Ben discussed the progress being made in treatments specifically for pancreatic cancer – soon to become the number two deadliest cancer in the United States behind lung cancer. Again, so much revolves around the challenges of targeting, in this case made even harder because of the way the cancer metastasizes early and aggressively. He confirmed that markers can evolve across the various secondary tumor sites, making it harder again, and pointed to immunotherapies (and the endogenous retrovirus targeting described above) as the most promising pathway, because the immune system has the natural ability to rapidly evolve its targeting in response. If the immune system is constantly trying to keep up with the cancer as it's changing, then great promise lies in finding ways to simply help the immune system along in this task.
mRNA CANCER VACCINES AND THERAPEUTICS
Ben confirmed the importance of the pancreatic cancer vaccine trials underway (currently a vaccine given after initial cancer treatment/remission to prevent pancreatic cancer returning) while cautioning that these were still only Stage I trials. Here again we are dealing with the magic of mRNA, for which two of the researchers at this facility, Katalin Karikó and Drew Weissman, won the Nobel Prize while I was visiting (How good is that? I’m claiming I’m a lucky charm in hopes I’ll get another invitation!)
mRNA is important because it is fast – we can go from sequencing to delivering a vaccine to the patient quickly, which is vital with an aggressive cancer. Furthermore, mRNA promises a rich future not only in vaccines, but also in cancer therapeutics – i.e. mRNA coding for proteins on the surface of the tumor, to teach the immune system to detect and attack it, AFTER the tumor is formed.
CANCER INTERCEPTION
The last new and promising frontier we discussed was cancer interception. Historically we’ve focused our interventions in the cancer timeline from the point at which cancer is detected onwards. We are now finding ways to intervene in the stages where we display precursors to cancer – i.e. before cancer cells have appeared. What genetic signals can we use? What pre-cancer therapies can we come up with? When does it make sense to apply them? These are some of the questions being tackled. I’m going to be adding more of this into my framework for the future of medicine! An excellent overview of the research pathways on the UPenn radar is in Kirsten Weir’s article, Can We Intercept Cancer? A New Frontier in Cancer Research. Paraphrasing Kirsten’s words, some of the promising research programs include:
Identifying and catching cells as they begin to develop into pre-cancers so we get the chance to halt or reversing that process. By using, for example, new single-cell sequencing technologies, and novel mouse models to characterize the changes in pre-malignant tissues. And by developing new blood-based biomarkers to identify pancreatic cancer at earlier stages (pancreatic cancer is notorious for going undiagnosed until it is advanced and difficult to treat) by applying machine learning to multiple biomarkers simultaneously as a way to increase sensitivity.
Inventing new genetic and molecular tools to complement the mechanical tools (i.e. cutting) we employ today. For example, UPenn is taking vaccines designed to prevent cancer recurrance after remission, and appying them to BRCA-positive participants who have a genetically high risk of cancer but have never had the cancer, to see if it works as a preventor. More broadly, they want to develop more chemical inhibitors to stop more types of tumors from developing.
Fundamental research to better understand the molecular biology in which a normal cell becomes a cancer cell. For example, developing a “human breast atlas” of tissue samples from women with and without BRCA mutations to map the various types of cells present in breast tissue and the molecular changes the cells undergo as they travel from healthy to malignant.
Developing more detailed understanding of environmental factors (eg diet) than can be modified (eg via dietary supplements) to reduce the onset of certain tumors, or to inhibit them from growing.
Information on the new Basser Center for BRCA-related cancers that Ben mentioned is here (BRCA: men and women with a gene mutation in either BRCA1 or BRCA2 are at heightened risk for certain cancers, including breast, ovarian, prostate, and pancreatic cancers).
ADVANCES ON ALL FRONTS
The story of cancer medicine is multi-threaded. It’s a story of early detection, of surgical removal, of radio- and chemo-therapies, of understanding lifestyle factors, of sequencing and pinpointing genetic factors, and lately of immunotherapies, but instead of one succeeding the other, each overlaps and complements and adds more weapons to the armory, and many of these weapons can be deployed in series or in combination.
Ben is talking about adding three more entire armories.
In effect, the future cancer weapons under development are moving both “upstream” in the cancer timeline (preventative/vaccines) and “downstream” (curative/therapies).
Like many scientists I’ve spoken to, Ben is super-excited about progress, and he left me feeling refreshed and thoughtful, continuing my own journey of optimism that took off when I first heard about Emily Whitehead’s succesful CAR-T treatment at UPenn more than a decade ago, then REALLY took off after my visits to MD Anderson and Broad Institute in 2018. We are truly in a golden age of medicine, and the future of healthcare is an amazing place.
Now, back to the next chapter of From One Cell – it really is a wonderful read!