Stanford Cancer Institute

SCI Women’s Cancer Center Innovation Award

March 2024

An SCI Women’s Cancer Center Innovation Award was awarded to Esther M. John, PhD, professor (research) of epidemiology and population health and of medicine (oncology), and Edgar Engleman, MD, professor of pathology and of medicine (immunology and rheumatology), for their proposal, “GPR65 expression, obesity, and breast cancer in a multiethnic population.” John is a cancer epidemiologist studying breast and prostate cancer to better understand the lifestyle, hormonal and genetic factors playing a role in these common cancers. She has a special interest in understanding cancer health disparities and cancer in Hispanics and African Americans, two understudied populations. Engleman studies the role of immune cells in the pathogenesis of cancers and other life-threatening disease. He employs mouse models for in-depth mechanistic studies and confirms clinical relevance by studying human tissues.

Obesity is a major public health challenge and is associated with a lower survival rate in breast cancer (BC) patients. Given substantial differences in breast cancer rates between racial and ethnic groups, obesity may also contribute to the long-standing and persistent racial and ethnic disparities in BC survival. Engleman’s lab recently discovered a molecular difference between obese and non-obese mice. Obese mice expressed higher levels of GPR65, an acid-sensing receptor, on tumor-associated macrophages, immune cells that can “eat” diseased and damaged cells. Moreover, tumors of obese mice grew much faster due to the immunosuppressive effects of this molecule. John and Engleman, through the support of the SCI Women’s Cancer Center Innovation Award, now plan to study the relationships between GPR65 expression and obesity. They will study tissue samples from a racially and ethnically diverse set of breast cancer patients diagnosed between 1995 and 2005. They will determine whether GPR65 is expressed in the breast tumor specimens of these patients, and assess whether expression varies by body mass index, race and ethnicity, clinical characteristics, and outcome (deceased vs. alive). The study will reveal whether the findings in mouse are also relevant in the human context, with the ultimate hope to use the findings to develop new breast cancer therapies.