The American Association for Cancer Research (AACR), the world’s largest association of cancer scientists and researchers, hosted its eighth special conference on Advances in Breast Cancer Research in Bellevue, WA from October 17-20, one of several AACR special conferences that focus on specific topics in basic, clinical and translational cancer research. This year’s conference was co-chaired by BCRF investigators Matthew Ellis and Charles Perou, along with Jane Visvader of the Walter and Eliza Hall Institute of Medical Research in Parkville, Australia. The three-day program was packed full with presentations from experts in basic and clinical breast cancer research. BCRF attended the meeting and had the opportunity to speak with Drs. Perou and Ellis to get their perspective on the meeting and research highlights.
BCRF: As Co-Chairs, what were your objectives in selecting the topics and presenters for this bi-annual meeting?
Perou: First and foremost, we wanted to pull in the top experts in each topic area. The family of AACR members provided that resource. In addition to having the best speakers, we also wanted to cover the latest topics, including genomics, hereditary genetics, the immune system and intratumor heterogeneity – the inherent genetic and biologic diversity of cancer cells within a tumor.
Ellis: Discovery happens at the interface between different disciplines and among people who have perspective on difficult problems like drug resistance or metastasis. The good thing about these meetings is that we have the leaders in the AACR cancer community discussing the big issues and challenges in breast cancer research.
BCRF: What were some of the highlights of the meeting?
Perou: The topics of stem cells, both normal stem cells and cancer stem cells, as well as the talks on tumor heterogeneity, really brought into focus how complicated breast cancer is. The tools we have now allow us to quantify heterogeneity [the diversity of cell types, genetic lesions, and gene expression within a tumor] in a way that we’ve never been able to do before. Because we’ve seen variability in how tumors respond to treatments, we’ve known that differences existed. Now we can quantify those differences. It’s important to keep in mind, though, that all the advances we’ve already made were made in the face of that heterogeneity. It has always been there. Tamoxifen and endocrine therapy were developed before we knew anything about tumor heterogeneity and are still very effective for a lot of women, even though they may have heterogeneous tumors.
Ellis: There have been some fantastic talks on several key issues. As a few examples, we heard a great talk questioning the true value of DNA sequencing in directing therapies in breast cancer. While the technology presents many theoretical possibilities, its clinical value right now is very controversial. In other words, it is not ready for “prime time.” The session on immunotherapy made it very clear that subsets of breast cancer, such as triple negative or some luminal breast cancers, will almost certainly emerge as candidates for the newly developed PD1/PD-L1 directed immunotherapies, which have worked well in other cancers such as melanoma.
BCRF: How long will it be before we can apply what we’re learning about tumor heterogeneity and cancer stem cells to personalized medicine?
Perou: The research in tumor heterogeneity is relatively young and we still don’t really know the impact it will have. Much of it could just be noise. We have the tools now to probe very deeply into the tumors and we’re entering a phase where we can begin to distinguish between the noise and the signal – or in other words, what is important. It is challenging and will take some time. We’ve known about cancer stem cells (CSCs) for decades, but it’s just in the last ten years that they have become an intense area of study. There are early-phase clinical trials under way now that are testing to see if drugs that target CSCs are going to be effective therapies and we’re anxiously awaiting those results.
Ellis: Some pre-clinical studies in which human tumors are transplanted into experimental models called patient-derived xenografts (PDX) have clearly shown that only a subset of cells within a tumor – you can call them cancer stem cells or tumor initiator cells – are capable of initiating a new tumor. If we can understand the vulnerabilities of that subset or identify the markers that can be targeted, we could achieve dramatic therapeutic effects in preventing metastasis. Kornelia Polyak gave an important talk that revealed how the different clones (genomically distinct cell populations) within a tumor cooperate to promote survival and growth of the tumor. We see the same things in the PDX models where certain clonal populations are driving different aspects of tumor behavior. These are paradigm–changing discoveries.
BCRF: A lot of the discoveries being discussed at the meeting could be helpful for understanding metastasis. As lead investigators on BCRF’s Evelyn H. Lauder Founder’s Fund projects in metastatic breast cancer, what specific advances do you think are going to be important to preventing and treating metastasis?
Perou: For reasons I don’t fully understand, metastatic breast cancer is probably the most understudied breast cancer and few therapies are effective against this disease. We don’t know who all the players are, but the suspicion is that things change from early breast cancer to late breast cancer. It’s absolutely critical to figure out what’s different and it will take a multidisciplinary effort, which is what the Founder’s Fund is all about – leveraging the expertise, resources and advances from every field. The Founder’s Fund allows us to study metastatic breast cancer on a massive scale to get the full picture, incorporating the study of DNA, RNA, proteins and other markers from metastatic tumors and the primary breast tumor.
Ellis: One of the things we’re going to see a lot more of is the use of PDXs for integrated “omics”, deciphering not only the gene expression, but protein expression as well. You can think about gene sequencing as a series of 0’s and 1’s, or a computer code with no picture. The proteins provide the picture. The integration of function in the context of gene mutations is where we’re trying to get to. That can lead us to new therapies and precision medicine.
BCRF: Any final comments?
Perou: I would like to acknowledge and thank the patients who donate their tissues to research. Even if the advances coming from these donated tissues may not help these actual patients, they most certainly will help future patients. None of what we’re doing would be possible without them.
Ellis: There is no better model for breast cancer than patients with breast cancer, and the PDX model is as close as we can get to that principle in laboratory research. I think in the next five to ten years it will become routine to do co-clinical trials, where every patient on the trial has an associated PDX “avatar.” It will be game changing in understanding the complexity of breast cancer and the metastatic process.
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