The Seventh Annual Basser Center Scientific Symposium, "BRCA1, BRCA2 and Beyond: An Update on Hereditary Cancer," held at the University of Pennsylvania on Tuesday, May 7, and Wednesday, May 8, featured Keynote speaker and Basser Global Prize awardee Maria Jasin, PhD, from Memorial Sloan Kettering Cancer Center. Dr. Jasin spoke with us about recent BRCA-related research.
Dr. Jasin: We're very interested in the DNA repair roles of these two proteins - and related proteins - because this will help us understand how tumors form to begin with. But also importantly to understand how tumors can be treated with different DNA damaging agents, and how the issues that arise - like reversion alleles - can impact the therapy response. Both BRCA1 and BRCA2 are fairly large genes, and fairly large proteins with mutations, and in different regions of the protein, the different regions of the gene, and so sometimes this can have an impact on how the cells respond - how tumor cells respond to treatment - but also how they revert. We're very interested in understanding the molecular nature of the repair roles that these proteins have, especially a focus on BRCA2 and how this can be important for therapy for patients with BRCA1 and BRCA2 tumors.
The Basser Global Research Prize is an incredible honor in part because I'm following people like Mary-Claire King, one of my heroes in the field for having mapped the BRCA1 gene in the first place, following David Livingstone who did some of the very basic analysis that initially got us interested in BRCA1 and BRCA2 to consider the DNA repair roles of BRCA1 and BRCA2. And the other recipients as well - just the impact that these people have made in the field and then to to come along and get the same prize it's it's really humbling. I am incredibly pleased. Another aspect is, frankly, I've had family members die of breast and ovarian cancer, one of whom I I know had a BRCA2 mutation, so it's impacted my family like it's impacted many families. I never expected to get into breast cancer research when I was a graduate student or even a postdoc, but I really feel privileged that the basic processes that we studied - homologous recombination and DNA repair - are so relevant to these these tumors.
I think a really major issue is therapy resistance. So having a BRCA1 or BRCA2 mutation does sensitize tumur cells to cisplatin to olaparib and other PARP inhibitors. And that's great, especially PARP inhibitors, which are relatively non-toxic, but the problem is there are resistant mechanisms that develop and so people may have a window of response, but are not cured, usually. There may be some super responders but the reversion problem, I think, is a major problem. Of course there are others as well, but the fact that DNA repair can be restored in BRCA1 and BRCA2 mutant tumors by restoring the reading frame, for example, of BRCA1 or BRCA2, I think is a major problem. I'm not sure how to get around that, but I think it's something that will need to be tackled as more and more people are treated with these DNA damaging agents.
I think the Basser Center has already impacted the field and will continue to impact the field in two major areas. One is financially supporting the research of BRCA1 and BRCA2 researchers. The second part is what we're doing today [at the Basser Scientific Symposium], bringing together BRCA1 and BRCA2 researchers to share their unpublished work to discuss new findings in the field and possibly to collaborate. And so I think the the Basser Center is is really doing a major service to the community in these two aspects.