Zhigang Charles Wang, MD, PhD

2009-2010 BCRF Project:
Co-investigators: Ross Berkowitz, MD and Ursula Matulonis, MD, Dana-Farber Cancer Institute and Brigham & Women's Hospital/Harvard Medical School, Boston, MA

The group at the Dana-Farber Cancer Institute and Brigham and Women's Hospital is examining the genetic link between breast and ovarian cancer which has been for a long time recognized by patients and their doctors. Ovarian cancer is a lethal disease with a mortality rate that exceeds all other gynecologic cancers but when treated at initial diagnosis, is highly sensitive to platinum-based chemotherapy much like a type of breast cancer called basal-like or triple-negative breast cancer that is diagnosed in women who have BRCA1 or BRCA2 mutations.

With support from The Breast Cancer Research Foundation, the researchers have generated a dataset of ovarian cancers, and found the two diseases, so-called "basal-like" breast cancer and high-grade serous ovarian cancer, are similar in a number of respects with genetic similarities, particular these two types of cancers do in fact show that they have similar unstable chromosomes. They have found a certain genetic abnormality on chromosomes 4, and 19 shared by both diseases and are in the process of investigating this further.

Recently, evaluation of total number of chromosomal breakpoints was found to be a good genomic marker for chromosomal instability to predict treatment response to the chemotherapeutic drug cisplatin in basal-like breast cancers. The researchers propose to explore whether this measure may also be useful for prediction of disease recurrence in ovarian cancer patients received cisplatin treatment. They will continue to collect more ovarian cancer samples in order to study a larger set of cancers for outcome when comparing them to triple negative breast cancer.

Mid-Year Progress Report:
At initial diagnosis, ovarian cancer is very highly sensitive to chemotherapy that consists of a platinum and a taxane, especially the most common type of ovarian cancer called high grade serous cancers which are also typically diagnosed in women with BRCA mutations. Unfortunately, most patients with advanced ovarian cancer develop a recurrence of their cancer because of the persistence of chemotherapy-resistant cells that eventually regrow. Triple negative breast cancer has been also found to be highly sensitive to platinum. Thus, given the clinical similarities between high grade serous ovarian cancer and triple negative breast cancer, the researchers postulated that genetic similarities must exist as well.

They have found the two diseases, so-called "basal-like" breast cancer and high-grade serous ovarian cancer, are similar in a number of genetic similarity and have similar unstable chromosomes. Recently, evaluation of total number of chromosomal damage measured as allelic imbalance (AI) was found to be a good genomic marker for chromosomal instability to predict treatment response to cisplatin in basal-like breast cancers. The scientists are exploring whether this measure may also be useful for prediction of disease recurrence in ovarian cancer patients.

Bio:
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.