May 19, 2022—(BRONX, NY)—The National Cancer Institute-designated Montefiore Einstein Cancer Center (MECC) has partnered with the Price Family Foundation to fund eight research teams developing novel cancer therapies and improving cancer outcomes for historically marginalized communities in the Bronx. The inaugural Price Family Foundation Health Equity Pilot Awards will provide $200,000 in funding over two years to each team and support basic science, translational, and clinical investigators focusing on cancers that are highly prevalent in the Bronx.
“Reducing cancer disparities means teasing apart and addressing the various causes of cancer—from the genetic and molecular to environmental and occupational exposures—that result in worse outcomes for Black, Brown, and other marginalized people in our country,” said Edward Chu, M.D., M.M.S., director of the MECC; vice president for cancer medicine at Montefiore Health System; and the Carol and Roger Einiger Professor of Cancer Medicine and professor of medicine, of oncology, and of molecular pharmacology at Albert Einstein College of Medicine. “We are grateful to have found a partner in the Price Family Foundation, which believes, as we do, in the importance of research that promotes health equity in the Bronx, which will inform cancer care here at our cancer center and throughout the country.”
Advancing Cancer Equity
The Bronx has one of the most diverse populations in the United States. Nearly 44% of people identify as Black or African American and 56% Hispanic; more than a third of residents were born in another country. Despite growing evidence that many molecular causes of cancer and disease progression are different in Black, Indigenous, and people of color (BIPOC) than in white people, BIPOC are often excluded from clinical trials, and their genetic makeup is ignored in preclinical studies testing possible treatments.
“The Montefiore Einstein Cancer Center is committed to leading the way in identifying new molecular alterations, targets, and signaling pathways that can be the focus for new drugs, immunotherapies, and novel treatments among people of color,” Dr. Chu added, noting that the research will also help inform new strategies for early detection, screening, and prevention for all patients.
The winning proposals include a range of investigations for a variety of cancers—including lung, head and neck, prostate, gynecologic, and breast—that disproportionately affect Black, Asian, Hispanic, and other non-white populations. The pilot studies will help generate data that the investigators can use to apply for federal funding to further their research.
The Winning Proposals
The 2022 Cancer Center/Price Family Foundation Health Equity awardees are:
Anne R. Bresnick, Ph.D., and Jonathan M. Backer, M.D., for their research to define the mechanism of signaling by S100A4, a protein that promotes cancer metastasis. S100A4 expression is higher in malignant human breast tumors than in benign tumors and correlates strongly with poor patient survival. Data from the Cancer Genome Atlas (TCGA) shows that there is a 23% increase in S100A4 expression in Black patients with invasive breast cancer. In addition, studies in mice show that S100A4 has a direct role in causing breast-cancer metastasis. Importantly, the cell-surface receptor for S100A4 in breast cancer cells remains unknown. Using proteomics approaches, the researchers will identify the S100A4 receptor and characterize the pro-metastatic signaling that occurs when it binds to S100A4. These studies will lay the groundwork for studying the role of the S100A4 receptor in animal models of breast cancer.
Robert Burk, M.D., for treating cervical cancer by targeting a protein that drives the disease, which is caused by infection with high-risk human papillomaviruses (HR-HPVs). No HPV-directed therapies are yet available. Compared with the average woman in New York State, Bronx women are 47% more likely to die from cervical cancer, and Latina women have the highest rates of the disease. HR-HPVs cause cervical cancer by expression of the E6 and E7 oncoproteins within infected cells, with E7 an especially important driving force. Dr. Burk has discovered a promising molecule called DTPap6 that binds to and inactivates E7 protein associated with HPV18, the virus responsible for nearly 40% of cervical cancer cases. He plans to study DTPap6’s molecular interaction with E7 with the goal of developing DTPap6 into a novel drug for treating cervical cancer.
Haiying Cheng, M.D., Ph.D., for her proposal to address the underlying factors leading to poor treatment outcomes among Black patients with EGFR+ non-small cell lung cancer (NSCLC) in the Bronx. A review of the Montefiore database from 2009 to 2015 showed that Black patients with EGFR+ NSCLC face worse survival outcomes than non-Black patients. The researchers will investigate biological factors and treatment barriers impacting the targeted therapy in Black patients with EFGR-mutated NSCLC. They will also investigate new immune checkpoints and tumor microenvironments in HIV+ lung cancer to advance therapies and improve outcomes in HIV+ patients with lung cancer.
Chaoyuan Kuang, M.D., Ph.D., is focused on making colorectal cancer more susceptible to chemotherapy—especially for Black and Hispanic patients, who appear to have more aggressive disease. The goal is to overcome colorectal cancer’s ability to resist apoptosis, or cell death. The targeted agent regorafenib works in part by inhibiting Mcl-1, a protein that interferes with apoptosis. However, tumors that overexpress Mcl-1 or fail to degrade the protein are more resistant to regorafenib. Dr. Kuang has found that Fbw7 mutations (present in 12% of colorectal cancers) may be markers for resistance to regorafenib. Moreover, in animal-model studies, he has shown that this resistance can be overcome by treatment with Mcl-1 inhibitors. Using cancer models established from MECC patients, he and his colleagues will study whether CDK9 inhibitors—a promising new class of anti-cancer drugs—can act as Mcl-1 inhibitors to make colorectal tumors more sensitive to regorafenib therapy.
Thomas Ow, M.D., M.S., for investigating why head and neck squamous cell carcinoma (HNSCC) tumors among Black patients are often resistant to cisplatin, a cornerstone of HNSCC therapy for more than 50 years. Examining tumors stored in Einstein’s HNSCC bank and cell cultures grown from patients treated at MECC, the researchers will determine whether cisplatin resistance among Black patients stems from upregulation of the NRF2 signaling pathway, which is known to play a role in cancer development and response to traditional treatments. His research team will also work to identify drug candidates that can effectively treat cisplatin-resistant HNSCC tumors in Black patients. The collaborative team will include the Ow Lab post-doctoral fellow Nitisha Shrivastava, Ph.D., the Einstein Genomics/Epigenomics Shared Core Facilities, and the Sandulache laboratory at Baylor College of Medicine (BCM).
Brendon Stiles, M.D., for his research investigating the relationship between the enzyme ART1 and the epidermal growth factor receptor (EGFR). Nearly one-third of all cases of non-small cell lung cancer (NSCLC) involve mutations to the EGFR protein, which are particularly enriched in Latin American populations. Additionally, studies at Einstein and Montefiore have found that Black patients experienced worse survival rates compared to non-Black patients. Although drugs called tyrosine kinase inhibitors (TKIs) block the activity of aberrant EGFR and have proven highly successful in treating NSCLC, immunotherapy has not worked as well against these tumors. Dr. Stiles has found that the enzyme ART1 is overexpressed on the surface of EGFR lung cancer cells and interferes with the body’s anti-tumor immune response. He will investigate whether inhibiting ART1 will increase the effectiveness of TKIs and of immunotherapy in patients whose tumors possess EGFR mutations.
Elyse Sussman, Ph.D., for her proposal to study prostate cancer patients being cared for at Montefiore who are undergoing androgen deprivation therapy (ADT). ADT is a widely used prostate cancer treatment that slows tumor growth by lowering testosterone levels. The incidence of prostate cancer in the Bronx for both Black and Hispanic men is the highest in all of New York State. Her research will investigate neurocognitive functioning in patients to gain insight into how low testosterone levels affect neural activity and brain structures involved in memory and attention. Using patient and animal models, the team will develop evidence-based intervention and after-treatment strategies that will minimize ADT’s cognitive impact on patients and improve quality of life. The ability to resume everyday functioning after treatment, to go back to work, and to enjoy and participate in life, is a primary concern for patients and their families. The multidisciplinary team also includes Benjamin Gartrell, M.D., Tiago Goncalves, Ph.D., and Mark Wagshul, Ph.D.
XingXing Zang, Ph.D., for developing novel drugs to help the immune system attack tumors. Cancer immunotherapy, in the form of immune checkpoint-inhibitor drugs, has revolutionized cancer treatment over the past decade. All too often, tumor cells produce molecules that thwart immune-system attack; the molecules bind to receptors (referred to as “checkpoints”) on immune cells, signaling the cells not to attack. Immune checkpoint inhibitors (ICIs) bolster the immune response against cancer by preventing tumor molecules from binding to T-cell checkpoints. Existing ICIs, however, work against just two checkpoint signaling pathways found only in T cells—key reasons immunotherapy drugs fail to help the majority of cancer patients. Dr. Zang recently discovered a third checkpoint pathway, called the KIR3DL3/HHLA2 pathway that the immune system’s natural killer (NK) cells possess. He plans to develop novel “bispecific” immune checkpoint inhibitors capable of inhibiting not only his newly discovered KIR3DL3/HHLA2 checkpoint pathway in NK cells but also inhibiting the previously known PD-1/PDL1 checkpoint pathway in T cells. This bispecific ICI could potentially work against cancers that don’t respond to existing ICIs—including liver, breast, bladder, and pancreatic cancers, all of which cause higher mortality in the Bronx than in New York State or the United States in general.
The pilot health equity awards were made possible by Price Family Foundation founder Michael F. Price, who had a strong interest in marrying cancer therapeutics, drug development, and social justice. Prior to his untimely passing in March 2022, Mr. Price, a member of the Einstein Board of Trustees since 2001 and a namesake of Einstein’s Michael F. Price Center for Genetic and Translational Medicine/Harold and Muriel Block Research Pavilion, learned of the winners.