Jeffrey N. Weitzel, MD: The BRCA Mutation and Cancer Genetics
Dr. Jeffrey Weitzel discusses the BRCA mutation and cancer genetics at the American Association for Cancer Research (AACR) Annual 2012 meeting in Chicago.
Jeffrey Weitzel, M.D. is Chief of the Division of Clinical Cancer Genetics at City of Hope. Dr.Weitzel’s multidisciplinary clinical and research program emphasizes the recognition and assessment of people at increased risk for developing cancer because of family cancer history or personal risk factors.
The Group Room at the American Association for Cancer Research (AACR) Annual Meeting 2012 was made possible, in part, by:
VIDEO TRANSCRIPT
Selma Schimmel, Founder & CEO, Vital Options International:
This is Selma Schimmel at the AACR annual meeting for the Group Room. This is the American Association for Cancer Research, we’re in Chicago and we’re now joined by our good Group Room friend, Dr. Jeffrey Weitzel, Professor of Oncology at Population Sciences, Chief of the Division of Clinical Cancer Genetics in the Department of Population Sciences at the City of Hope Comprehensive Cancer Center in Duarte, California.
Jeffrey N. Weitzel, MD, Chief, Clinical Cancer Genetics, City of Hope Cancer Center, Duarte, CA
Good morning, Selma. Pleasure to be here.
Selma Schimmel:
How are you?
Jeffrey N. Weitzel, MD:
Good.
Selma Schimmel:
The promising news is that BRCA positive patients may respond in a very positive way to some of these new therapies. And let’s talk about what’s in the pipeline and what we’ve been seeing, and why do we perhaps see that BRCA patients have better response to treatment.
Jeffrey N. Weitzel, MD:
Well you know, genetics can give us insights, and what’s again the whole theme of this meeting has been about understanding the genomic and genetic underpinnings of cancer whether it’s an acquired problem or an inherited problem. And the story, at least, as far as BRCA and its unique susceptibility to treatments has to do a lot with even fundamental concepts and tumor suppressor genes – that is, you have two copies, you lose one copy in the germ line, you lose the other copy in the tumor, now it doesn’t have that gene anymore – in its expression, and those genes are important in DNA repair.
Cells spend their whole life repairing DNA because there’s just things all around us in terms of and when that function goes away the cells become scrambled and turns their DNA and then they get cancer. Well turns out that that’s also the Achilles heel of those tumors, and so when these therapies attack different pathways now and that’s where sort of one of the people who champion this synthetically thality concept these tumors are susceptibly suitable two things that attack the DNA repair pathways, the parts that were being used as a salvage mechanism for the cells. And so it’s interesting to see that, for example, it’s not just new medicines; it’s old medicines that work better in these individuals.
There’s been an observation for some time that women with ovarian cancer who have BRCA mutation do better than the women who don’t have the BRCA mutation in terms of survival. We didn’t understand why but the observation has been there, now we know why. It’s because their tumors were uniquely sensitive probably to platinum-based therapy, and the platinum drugs have a unique place now probably in treatment of BRCA associated patients, at least it’s evolving that way because they do better in that context.
Also, the genes aren’t equivalent; BRCA 2 seems to do better than BRCA 1 we’ve recently seen, demonstrated that ourselves in a paper that we’ve put out and there’s a couple of others that have come out also about this. So if you take the old drugs like platinum, and then parp inhibitors – which I understand others have spoken about here on your show – those inhibitors are unique and exciting for a couple of reasons. One is, they don’t actually attack the pathway the BRCA is on, they attack the salvage pathway, sort of a hidden up or down process, and so that combination of therapies – again, they talk a lot about good combinations in this meeting – that combination can, we believe, enhances cells without making somebody particularly sick. Don’t lose your hair, we don’t pre-medicate nausea because these drugs are very well tolerated. In fact, some of these women when they get a response even to stabilize disease, which is what we’re seeing a lot of it’s like a drug holiday for them. They’re not constantly going to the bathroom, they feel reasonably well while they’re on these medications.
Selma Schimmel:
But many of the studies right now are not parp as a single agent. They tend to be parp with…
Jeffrey N. Weitzel, MD:
…in combination. So I can address it, but in parp as a single agent I do want to mention because it is we’re in two face two studies and it did demonstrate effect in both ovarian and breast, it actually seemed to have more effect in breast because they had less exposure to platinum drugs than some of the hypothesis, whereas in ovarian cancer patients it became refractory. They develop resistance mechanisms may be along that pathway. So while it has single-agent effect we’re studying it now at the City of Hope currently looking at carboplatin in combination with the parp inhibitors.
Selma Schimmel:
Is this an open study?
Jeffrey N. Weitzel, MD:
It’s an open study currently at the City of Hope, and at the California Cancer Consortium which is a number of institutions.
Selma Schimmel:
Are you looking for more patient to crew?
Jeffrey N. Weitzel, MD:
We’re always looking for more patient to crew. I think our current level of study is full but we’re open again shortly so we’re always looking for it. And because we’re interested in this pathway, there are going to be other protocols coming along that have BRCA focus, and same for the ovarian cancer realm – BRCA focus – because we are looking for that niche that might have a therapeutic advantage. And so we’re very encouraged by the study so far. We’re using lower doses of carboplatin and getting very effective responses in women who were multiple treated with breast cancer. We submitted to ASCO that was accepted and shows a pretty nice clinical benefit rate, a couple of CRs and so we’re very encouraged especially for a population that’s desperate for new avenues.
Selma Schimmel:
And are we also looking at parp inhibitors for some of the other BRCA-related tumor types?
Jeffrey N. Weitzel, MD:
That’s a great question, Selma because we’re now moving away from a tissue or tumor type therapeutic strategy to a genotype related therapeutic strategy. And I think, so absolutely, there are papers published anecdotally but if people being treated, for example, platinum with pancreatic cancer and getting complete response from metastatic disease even though it’s unique, that’s the exception but sometimes it’s the exceptions that give you the insights. So there are studies on-going around the world, actually, particularly Rizels in Britain looking at prostate cancer in men who are BRCA carriers so we need to be able to determine if they have that same therapeutic advantage there as you do with breast and ovary.
Selma Schimmel:
Doctor Jeffrey Witzel, Professor of Oncology and Population Sciences, Chief of the Division of Clinical Cancer Genetics in the Department of Population Sciences, at the City of Hope Comprehensive Cancer Center in Duarte, California.
Jeffrey N. Weitzel, MD:
Thank you, Selma.
Selma Schimmel:
Pleasure.
END OF VIDEO