Defining Differences in BRCA-Driven Cancers
Dr. Avantika Lal, PhD, Pathology
Dr. Avantika Lal is a post-doctoral fellow in Dr. Arend Sidow's lab at Stanford University. Her research is broadly focused on developing inventive ways of gaining a deeper molecular understanding of breast cancer. In this video we learn about the surprising gaps in the current body of BRCA-related research, and the novel approaches Dr. Lal is using to address these issues. Her most ground-breaking work has involved deciphering the genetic differences in BRCA-driven breast cancers versus those arising from environmental causes. The video explores the unique and innovative computational methods Dr. Lal is taking to distinguish the genetic make-up of different types of tumors. Her research has uncovered exciting new ways to think about BRCA-driven cancers, and could potentially give oncologists new ways of treating and diagnosing breast cancer.
My name is Avantika, and I'm a post-doctoral fellow in professor Arend Sidow's lab at Stanford University. Broadly, my research tackles the genetic changes that take place in different kinds of tumors, most particularly breast tumors. Specifically, one of the things I'm really interested in right now is, on a genetic basis, what makes tumors in people with hereditary BRCA mutations different from other kinds of breast tumors.
How is your research helping to understand BRCA-driven tumors?
Well, if you think about it, the cause of cancer in people with BRCA tumors is completely different from all others because they have a hereditary mutation that affects the functions of their cells and predisposes them to get cancer, which is not the case in people who get cancer because of sporadic or environmental causes. It actually really astonishes me that people have been studying the BRCA genes for so many decades, and they are the most famous genes in the world of hereditary cancer, but we don't actually know how they work. We don't actually know what is wrong in these patients and what changes happen in their cells that causes them to have such a high rate of cancer. Until we understand the mechanistic basis of these cancers, how do we treat them effectively?
What differences have you found in BRCA-related cancers?
Compared to regular sporadic cancers, BRCA tumors have DNA damage on a much larger scale. Whereas sporadic cancers are likely to have mutations in single bases of DNA, and many such mutations, BRCA tumors are much more likely to have rearrangements, and deletions, and duplications of very large segments covering thousands or tens-of-thousands of bases of DNA which affect a much larger number of genes.
How can this information help cancer patients?
Well we now know that the underlying genetic damage that goes on in patients with BRCA tumors in very different from what's happening in sporadic breast cancers. In fact, we even know that the genes that are damaged in BRCA tumors are different from other cancers. So this knowledge can hopefully help us develop specific treatments and chemotherapy for these patients. Another thing that we can do with this information is, since we that know that patients with BRCA tumors are likely to develop cancer through larger genetic changes such as duplications and deletions of DNA, we could monitor people with a family history of BRCA, and look for the early stages of cancer by looking for these specific kinds of changes.
What do you find most interesting about studying breast cancer?
What really interests me about this problem is that we talk about cancer and breast cancer as if it's a single disease, but really cancer is incredibly diverse at the genetic level, and it would be accurate to say that every person's cancer is different. We're at this incredible stage in medicine where we can actually treat people based on their individual genetic data rather than just having a, one-treatment-fits-everybody kind of medicine. So I'm really interested in that, and I'm really interested in gathering genetic data from patients and using that to understand what the right treatment for them is. This is a great step in that direction.
About the Speaker
Dr. Lal's research focuses on developing and applying machine-learning methods to understand genomic data. Cancer evolves through many kinds of changes in our genomes, including mutations in specific genes, deletion of large segments of DNA, or subtle changes in gene activity. High-throughput experiments based on DNA sequencing allow us to measure these changes, but complex computational methods are required to analyze such datasets and derive insights about cancer evolution. Currently, Dr. Lal is using sequencing and machine learning to study the differences between the genomes of BRCA and sporadic breast tumors. Understanding the unique properties of BRCA tumors can reveal the specific pathways by which BRCA mutations lead to risk of cancer, and can help develop specialized treatment and monitoring for BRCA carriers.