As the new person appointed to the White House Cancer Advisory Board, Ashani Weeraratna will help chart the course for cancer research at the national level by embracing diversity, an approach that could become one of our best weapons. in the fight against cancer.
Weeraratna, Bloomberg Distinguished Professor of Cancer Biology, emphasizes the need to consider age, race and gender to determine which cancer treatments are most effective for each patient. Her efforts have also been recognized by the National Cancer Institute, which recently named her one of five researchers who “are accelerating our understanding of cancer into the future.” Specifically, they cited Weeraranta for “reshaping clinical practice with research findings on age-related differences in response to cancer treatment” and for her commitment to helping develop a diverse and inclusive next generation of cancer patients. cancer researchers.
“Without a diverse perspective, we will never cure cancer. And that is my ultimate goal.”
Weeraratna is Professor and EV McCollum Chair in Biochemistry and Molecular Biology and has an appointment at the Sidney Kimmel Comprehensive Cancer Center. She is studying the molecular mechanisms involved in metastasis and how tumor microenvironments affect cancer progression and resistance to therapy. Weeraratna has shown that age-related changes in the microenvironment can contribute to multiple aspects of melanoma formation and development as well as resistance to treatment.
In his next book, Is cancer inevitable?, Weeraratna describes the mechanisms of cancer and how teams like his are finding ways to reduce its deadly impacts. This is a compelling account of his journey from his formative years in Sri Lanka and Lesotho to his studies in the United States and then to appointments to elite government and academic institutions. The book, due out in December, is part of Johns Hopkins Wavelengths series from Johns Hopkins University Press, a collaboration with the Office of Research that aims to bring the work of distinguished Bloomberg professors to a wider audience.
How do age differences lead to varying responses to cancer treatment?
One of the things we found, for example, is that as we get older the non-cancerous cells in your skin also age, and they start to secrete different factors than younger ones, which can initiate changes within the tumor. cell. So, for example, we found that older fibroblasts, cells that produce much of the structural structure of many tissues, secrete different types of lipids or fats. This initiates a change in the tumor cells which causes them to express a fatty acid transporter which takes these fats, brings them through the membrane inside the cell, and then changes the metabolism of the tumor cells so that they do not. respond more to treatment. . What we learned from this study is that there is actually a specific receptor that we can target to tumor cells in this population that can now make them more sensitive to treatment again.
What do these results mean for future cancer research and clinical practice?
I think the importance of our discovery lies in showing that when we design and develop drugs in preclinical studies that are not suitable for the age groups that we are actually treating in the clinic, we are missing an enormous amount of ‘information. What we’re trying to do is fill that knowledge gap. Especially when it comes to thinking about therapies, we tend to design all of our preclinical studies using six-week-old mice, which is like designing a study on 14-year-old humans, instead of looking at mice that may be 12 years old. at 18 months, which would more accurately reflect the cancer patient population, as the incidence of most cancers increases dramatically after the age of 55. Really, this is the age group in which we should model our studies. We need to make sure that we design clinical trials that include older people and that monitor their response differently.
Clinically, we want to understand why patients do not respond to treatment. When treating melanoma patients with targeted therapy, for example, older patients do not respond as well as younger patients. Scientifically, I have always found this fascinating because, especially in melanoma, we are dealing with a targeted mutation in a single gene with a single drug. One would expect that if a drug that targets a particular mutation cuts the signaling pathway, it should work and nothing else should matter. But in fact, the microenvironment – the cells, molecules, and structures such as blood vessels that surround the tumor – is critically important and speaks to what is going on in the tumor cell. Finding age-related differences in response to treatment also means that we can potentially design drugs that will specifically target older populations to improve response. For example, immunotherapy might have better results in older patients than targeted therapy. Conducting more future research with older cancer patients will hopefully help us find more effective clinical approaches.
Why do you think it has taken so far to see that there is an age-related difference in response to treatment?
I think the field of aging and the field of cancer, until recently, were very separate. Research on aging reflects on longevity and how you increase longevity. The field of cancer is of course focused on cancer. Personally, I had a very unique experience where I moved from a cancer-focused environment to the National Institute on Aging for a while, which allowed me to see aging as a disease. itself, then take those observations and apply them to our cancer work. I am a strong supporter of the microenvironment; when you are in one environment it can really shape the way you think and behave in relation to another environment. I was fortunate to be able to move from a cancer research environment to an aging research environment and sort of bring together many of these observations. This interdisciplinary training has placed me in a unique position to do this type of research, especially when it comes to thinking about what happens during aging and asking questions such as “What changes are happening?” occur during aging? Or “How can these changes influence the progression of cancer?” “
After accelerating our understanding of cancer in the future, where do you hope to conduct your research next?
Right now we have specific targets that we have identified that can really improve response to therapy. Concretely, there are molecules which are expressed either in the cells of the microenvironment, or on the surface of the tumor cells which one can target in order to kill the tumor cells without affecting too many non-cancerous cells. Now I want to develop them into drugs for clinical trials to see if we can extend the lifespan of our cancer patients. By thinking globally, in the long term, I hope to change the way we approach the studies that we do. Our studies were, in a way, resolved. Of course, we’ve accomplished great things on the cancer spectrum – if you have cancer now, you’re probably going to live a lot longer than you did 20 years ago. But despite this, we have to start to understand the nuances. What does it mean to be older? What does it mean to be a woman against a man? What does it mean to be a person of color? How does your race play into your reaction to drugs? These are all crucial next steps for us to understand parameters beyond aging, such as gender and race.
“Our studies show that understanding what’s different between patients helps us treat them better. And I think that’s so important.”
What are the most exciting moments in your research?
A lot of the work in my lab is done by interns, who are really the ones who are leading a lot of research and making amazing discoveries. They are the essential engine of science. The most exciting moments are easy to identify: it is when a student shows up in my office with a new result and says to me: “look at this! To this day, a seemingly simple strip on a gel has made me incredibly horny. These are the times we live for. What excites me about this research is that it is really a new field. And, in a way, that inspires me to promote diversity in science and understand what it means to take a diverse approach to science itself, because what our studies show is that understanding what is different between patients helps us to treat them better. . And I think it’s so important.
You are a strong advocate for young teachers, women, immigrants and people of color in science. Why do you see your advocacy work as such an important part of your role as a researcher, and what do you hope to accomplish?
I grew up in southern Africa during the apartheid era. I was able to see first-hand what it meant to be excluded from spaces in which you were not supposed to be, physically, like in a restaurant, but also intellectually: the fact that many people could not contribute to a conversation made this conversation less round and less full. And I see that in science. We see that women and underrepresented minorities have calmer voices than they should in science because of how the systemic structure has been for a very long time. It’s important for me, as someone who’s been through a lot of hardship as a woman of color in science, to make sure the next generation doesn’t go through this. I know how valuable the voices of others are, and I want science to be a space where we can bring and hear all of these thoughts and conversations. Without a diverse perspective, we will never cure cancer. And that’s my ultimate goal.
I also hope to inspire generations of women to persist when sometimes they feel like they just want to give up and walk away. I want to make sure that when I hang up my lab coat for the last time, we think about race, gender and age in our clinical trials and that we design our drugs to benefit all populations, not just a single population. And I hope that through outreach work, we can start to dismantle the mistrust of populations of color in hospitals and really engage people in these clinical trials and get them treated, get the help they need.
