Researcher Grants Report

Cancer Center Director Hails Importance of Philanthropy for Reasearch

Gustavo Leone, PhD, Director of the Medical College of Wisconsin Cancer Center (MCWCC), the Dr. Glenn R. and Nancy A. Linnerson Endowed Chair in Cancer Research, Senior Associate Dean of Cancer Research, and Professor in the Department of Biochemistry, is a tireless advocate for philanthropic research support. Speaking at a recent WBCS event, Dr. Leone emphasized the critical role of philanthropy to fuel innovative research ideas into cancer research advancements.

Dr. Leone works closely with the Froedtert Clinical Cancer Center to ensure that scientific breakthroughs made possible by the support of WBCS and other philanthropic entities are translating into treatment options and that patients benefit from the most current therapies available.

MCW scientists have successfully leveraged the significant WBCS investment of $7.09 million in earlystage, promising research into an additional $90.6 million of external research support, for an overall breast cancer and prostate cancer research impact by WBCS of $97.69 million.

To cite just one current example, WBCS philanthropy furthered research in the lab of Marja Nevalainen, MD, PhD (see synopsis below) that has led to Dr. Nevalainen’s receiving a highly competitive and prestigious NCI R01 grant. The Nevalainen NCI-R01 project is important because of its translational significance and potential for high impact on disease.

As an MCW community engagement leader, Dr. Leone never fails to emphasize the critical importance of philanthropy as an igniter for new avenues of research. Funding innovative ideas that translate into larger external grants both advances discoveries in immunotherapies and precision oncology and leads to an understanding and reducing of cancer treatment disparities.

WBCS and its Scientific Review Committee approve support for only the most promising, peer-reviewed research proposals that fall within its mission. While this important stewardship has led to a 12:1 return on our philanthropic investment to defeat breast cancer and prostate cancer locally, the partnership of our all-volunteer charity with collaborative MCW researchers has the potential for a global reach that might otherwise not be possible.

Dr. Leone recently celebrated his second anniversary as Director of MCWCC. Thinking about the tasks ahead, Dr. Leone noted with his unfailing optimism, “Our mission is set and goals are lofty, and the road to achieve them is the best part.”

As a strong MCWCC philanthropic partner, WBCS looks forward to continuing to work with Dr. Leone, as we raise funds critical to investing in science with the potential to lead to cures. ~

Independent Seed Grants 2020 & 2021

Third Year No Cost Extension Approval Leading To A New NCI RO1 Award

Carol Williams, PhD, Joan K. Van Deuren Professor in Breast Cancer Research, Director, Cancer Biology Program, MCW Cancer Center, Professor of Pharmacology and Toxicology A Novel Strategy to Suppress the Activity of Oncogenic Small GTPases in Breast Cancer Breast cancer remains a leading killer of women, despite much progress made in the diagnosis and treatment of the disease during the past decade. Our research has been investigating the mechanisms that promote breast cancer, with the goal of identifying new ways to treat breast cancer. Our studies focus on the protein called SmgGDS that helps breast cancer cells multiply and form tumors. We discovered that breast cancer cells make two forms of SmgGDS, named SmgGDS-607 and SmgGDS-558. We are investigating how these two forms of SmgGDS function in breast cancer, in order to determine how to stop SmgGDS from promoting tumor formation.

Yunguang Sun, MD, PhD, Assistant Professor, Pathology & Laboratory Medicine New Therapeutic Approaches to Estrogen Receptor-Positive Breast Cancer. 80% of newly diagnosed breast cancer (BC) cases are Estrogen receptor-α positive (ER+). More than 20% of patients with ER+ BC are projected to die from recurrent disease despite anti-estrogen therapy. Lack of effective preclinical models of the aggressive and spontaneously metastasizing ER+ Luminal B BC subtype has hampered efforts to find better treatments to 1) overcome established endocrine resistance in metastatic BC, or 2) block development of endocrine resistance in latent metastases frequently occurring in patients with Luminal B ER+ BC. We will test selected drugs in mice with already established endocrine resistant BC lung metastases and determine using therapy naïve tumor models whether combinations of these drugs with anti-estrogens can eliminate micro metastatic BC lung metastases and cure the mice.

Marja Nevalainen MD, PhD, Professor, Eminent Scholar, Dept. of Pathology and Pharmacology & Toxicology “Stat5 and Anti-Androgen-Induced Metastatic Phenotype of Prostate Cancer” Treatment options for metastatic prostate cancer (MPC) are limited to androgen-deprivation-therapy. The new-generation antiandrogen, Enzalutamide dominates the clinical space and is FDA approved in pre- and post-chemotherapy settings. Resistance to Enzalutamide arises within 3-6 months, with patients developing terminal castrate-resistant (CR)-MPC. There are no effective therapies for CR-MPC. Our data support a novel concept that Stat5 promotes development of Enzalutamide-resistant prostate cancer (ERPC). We previously showed that Stat5 induces metastatic behavior of PC cells. Also, Enzalutamide has been shown to induce metastatic phenotype of PC. Our new data show that Enzalutamide induces Jak2-Stat5 activation in PC. This proposal will test whether Enzalutamide induction of Jak2-Stat5 signaling in PC mediates Enzalutamide promotion of CR-MPC and may result in a new therapeutic strategy for ERPC by exploiting Jak2-Stat5 pathway inhibitors that are in clinical development for leukemias. Our goal is that this project results in development of a new therapy for ERPC.