Assistant Professor of Surgery
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Harvard Medical School
Triple-negative breast cancers (TNBCs) are often aggressive, commonly recur and are frequently lethal. TNBCs are defined by absence of the estrogen, progesterone and HER2 receptors. Therefore, common treatments are ineffective, and patients must be treated with more toxic chemotherapy. Although chemotherapy can be effective for early-stage TNBC, patients often progress to metastatic disease, in which cancer invades other tissues. Studies by Drs. Zhao and Wang found that PTEN, a protein that suppresses tumor growth, is largely absent in a large collection of samples of TNBC metastases. They have previously shown that PTEN-deficient cancers are sensitive to inhibition of the enzyme PI3K-p110-beta and block PTEN-deficient tumor growth. These findings led to a clinical trial with a PI3K-p110-beta selective inhibitor in patients with advanced cancer. In the coming year they will investigate PTEN-loss in TNBC metastasis, and evaluate the use of selective PI3K-p110-beta inhibitors to treat metastatic TNBC. They have developed a large cohort of patient-derived cancer models that closely mimic the behavior of patients’ tumors, and will now screen for novel drug treatments to use in combination with PI3K-p110-beta inhibitors to treat metastases from PTEN-deficient TNBC. This study will focus exclusively on metastatic TNBC cancer, trying to find a way to save patients from this extremely lethal condition.
Zhigang Charles Wang received his MD from Shanghai Second Medical University in Shanghai, China and his PhD in Microbiology and Immunology from New York Medical College. His resident training in pathology was completed at Rie-Jing Hospital in China and his post-doctoral training occurred at the Center for Blood Research at Harvard Medical School and at the National Institute for Dental Research. At the latter, he served as Senior Staff Fellow. Dr. Wang is an active member of the American Association for Cancer Research and currently an Assistant Professor of Surgery at Harvard Medical School, Dana-Farber Cancer Institute and Brigham & Women's Hospital.
Dr. Wang's research is interested in the genetics of breast cancer, with a particular focus on the heterogeneity of the disease which he studies through detailed mapping of chromosomal lesions and analysis of genes critical for its pathogenesis. He has worked closely with other BCRF grantees, Drs. Andrea Richardson and James D. Iglehart, to discover the high genetic instability and signature chromosomal alterations of a highly malignant subtype of breast cancer (the basal-like tumor). He has also discovered a significant association between copy gain of chromosome 8q22 and distant metastasis in breast cancer patients that received post-surgery chemotherapy. Furthermore, studies are underway to identify critical genes in this chromosomal region as therapeutic targets and prognostic markers.
Recently, he became interested in the genetic similarities between serous ovarian cancer and basal-like breast tumors. In collaboration with Drs. Ross Berkowitz and Ursula Matulonis at the Brigham and Women's Hospital and Dana-Farber Cancer Institute, he has begun a comprehensive genomic analysis of breast and serous ovarian cancer to discover the common chromosomal alterations and genes critical for the pathogenesis of both diseases.