Assistant Professor of Surgery
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Harvard Medical School
Dr. Wang is part of two collaborative BCRF projects focused on the application of tumor genomics to improve breast cancer outcomes. His work with BCRF colleagues Ross Berkowitz and Ursula Matulonis seeks to identify the common genetic features of breast and ovarian cancers. They are using information from collaborative clinical trials, publicly available data from researchers from around the world and emerging technologies to accelerate progress and leverage discoveries made in one disease to benefit the other. The team is credited with showing that the accumulation of genetic mutations in breast and ovarian cancers influences how the tumors respond to treatment. They are using this information to better understand drug resistance and to identify new biomarkers and therapeutic targets. Work in the coming year will focus on analyzing the amount and types of mutations to determine if a specific mutation “signature” can be used to predict response to two types of drugs that may be particularly useful in certain breast and ovarian cancers; platinum-based drugs, such as cisplatin, and PARP inhibitors, a newer class of drugs that inhibit the ability of cells to repair damaged genes and DNA. These innovative studies are incredibly important in advancing our understanding of drug resistance and will lead to better treatment strategies for many aggressive cancers.
Drs. Wang, Iglehart and Richardson are part of an interdisciplinary collaborative group which includes other BCRF investigators, focused on the genetics of triple negative breast cancer (TNBC). Their collective work led to the identification of a number of different tumor biomarkers that can predict whether a woman’s tumor will respond to a drug called cisplatin, which belongs to a class of drugs referred to as DNA damaging agents. These biomarkers can be measured by doing different types of genomic testing of a woman’s breast cancer tissue. The research team recently discovered that high levels of a gene called BLM enhances the tumor killing effect of cisplatin and in the coming year they will work to understand how BLM is affecting cisplatin response. In addition, the researchers recently found that the number of mutations in a tumor is predictive of survival in women with ovarian cancer: the higher the number of mutations, the better the cancer responds to cisplatin treatment and the longer the woman survives. They will now test to see whether the same may be true for women with breast cancer. These studies will lead to a better understanding of the mutational processes that promote to cancer development and how the burden of mutation may predict for patient outcomes.
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.