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Global Collaboration on Immunotherapy and Drug Resistance Research

BCRF-sponsored symposium connects scientists, clinicians, and private industry to share research developments.

Several BCRF investigators recently joined fellow researchers and clinicians from around the world to present some of the latest progress in breast cancer immunotherapy and drug resistance research.

The Breast Cancer Think Tank Symposium was established by Drs. Marc Lippman of Georgetown University and the late William McGuire 30 years ago to bring breast cancer researchers and clinicians together with the pharmaceutical and biotech industries to discuss recent developments in the field. Since Dr. Mcguire’s untimely death in 1992, the meeting has been organized by Drs. Lippman and C. Kent Osborne of Baylor College of Medicine.

The symposium’s format encourages communication to identify new strategies for breast cancer diagnosis, treatment, and prevention. “This meeting is unique in that participants work together for a full week, which greatly amplifies the opportunities for new collaboration and study,” Dr. Lippman said.

BCRF was proud to sponsor the symposium as it celebrated its 30th anniversary in January. This year’s think tank highlighted key topics, including drug resistance in anti-estrogen therapy (endocrine therapy), immunotherapy, and intra-tumor heterogeneity.

Drug resistance in endocrine therapy

Endocrine therapy targets the interaction of estrogen with the estrogen-receptor (ER) and has significantly decreased mortality in women with ER-positive breast cancer. Unfortunately, about 25 to 30 percent of patients who undergo endocrine therapy experience breast cancer recurrence or metastasis (breast cancer that has spread to other tissues) because they develop endocrine resistance.

BCRF Invesigator Dr. Benita Katzenellenbogen of the University of Illinois at Urbana-Champaign discussed ongoing work in her laboratory based on her previous finding that FOXM1 gene and family of proteins are key factors in resistance to endocrine therapy. Dr. Katzenellenbogen and her team have identified potential new targets related to FOXM1 function that restore sensitivity to chemotherapy and endocrine therapy and are continuing work in this area.

Although CDK4/6 inhibitor therapy has been utilized in metastatic patients to overcome endocrine therapy resistance, some patients also develop a resistance to it, as well. BCRF Investigator Dr. Vered Stearns of Johns Hopkins School of Medicine highlighted a novel mechanism of resistance to CDK4/6 inhibitor therapy. Her group used data from a clinical study in metastatic patients to identify potentially targetable genetic alterations in the HER2 gene in patients with ER-positive/HER2 negative breast cancer. These alterations can be important drivers of CDK4/6 inhibitor therapy resistance.

Dr. Geoff Greene of the University of Chicago presented his lab’s research on the development of novel anti-estrogen compounds to reduce resistance to endocrine-based therapy. Using existing drugs that target the estrogen receptor, Dr. Greene’s group hopes to design the next generation of inhibitors capable of treating or preventing drug resistance.

Finding the right targets for immunotherapy

Immunotherapy uses the power of the immune system to attack cancer cells. Recent studies suggest immunotherapy has the potential to improve outcomes for breast cancer patients in combination with chemotherapy.

Since chemotherapy has been shown to increase immune checkpoint inhibitor proteins, Dr. Bert O’Malley of Baylor College of Medicine discussed the importance of timing immunotherapy and chemotherapy in order to kill breast cancer cells in a way that avoids the immunosuppressive effects of checkpoint inhibitor proteins.

To advance immunotherapy in breast cancers, researchers are working to identify potential targets other than checkpoint inhibitors. Dr. Douglas Yee of the University of Minnesota presented his work on insulin receptor-A, especially since insulin receptor-A expression does not appear to be affected by endocrine treatment resistance. He hopes this may be especially applicable in patients with ER-positive breast cancer who are less likely to respond to drugs targeting checkpoint inhibitor proteins.

Diversity within a single tumor: intra-tumor heterogeneity research

Breast cancer is a complex disease, made even more so by intra-tumor heterogeneity—meaning that a single tumor is comprised of many genetically diverse cells. Tumor heterogeneity is believed to be a driving force in drug resistance, recurrence, and metastasis.

BCRF Investigator Dr. Matthew Ellis of Baylor College of Medicine discussed his work using proteogenomics, a discipline based on a combination of protein and genomic analysis, to identify new breast cancer cell subtypes that may be involved in metastasis.

BCRF Investigator Dr. Adrian Lee of the University of Pittsburgh discussed the power of single cell sequencing to characterize individual cells within a tumor that may be specific drivers of metastasis.

Dr. Mohamed Bentires-Alj of the University of Basel presented his research on the factors that contribute to breast cancer cell dormancy and possible triggers that cause dormant cells to metasticize.

The Breast Cancer Think Tank Symposium promotes unique collaborations across institutions, industries, and disciplines. Providing researchers with the opportunity to share ideas and developments is key to progress.

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