Samuel C. Mok, Ph.D.
1987, The Chinese University of Hong Kong
The University of Texas M. D. Anderson Cancer Center
Department of Gynecologic Oncology
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Samuel C. Mok, Ph.D. 1987, The Chinese University of Hong Kong The University of Texas M. D. Anderson Cancer Center |
Research Interests:
Our laboratory has a primary research focus on the use of molecular biological techniques to investigate the pathogenesis of invasive ovarian cancer and borderline epithelial ovarian tumors. Our lab has pursued studies of genetic changes in tissues from invasive ovarian cancer and borderline tumors to better understand the potential relationship between these two entities and to determine basic mechanisms of development. Our studies indicate that the pathway of pathogenesis of borderline ovarian tumors is distinct from that of invasive ovarian cancers. Furthermore, we've also shown that advanced ovarian cancer is unifocal in origin, thereby indicating the opportunity for early diagnosis. Our lab's ongoing research projects involve the use of oligonucleotide microarrays and SNP arrays to identify differentially expressed genes and DNA copy number abnormalities in microdissected primary and recurrent ovarian tumor tissue samples of different histological types, stages, and grades, correlation between expression profile data and clinical outcomes including chemoresponse and survival, and functional studies of genes that may be of clinicopathological significance. These studies will generate biomarkers for the development of a pathway model for the genetic progression of ovarian cancer, provide insights into their roles in ovarian carcinogenesis, provide markers for early diagnosis of ovarian cancer, and new therapeutic targets for treatment.
Our lab has also been exploring changes in the stromal component in various types of early stage ovarian tumors by comparing them with that in the normal ovary or fallopian tube. Recently, we have successfully established 3D normal ovarian epithelial and cancer spheroid and stromal fibroblast co-culture models. These models have allowed us to manipulate the ovarian cells in an isolated stromal-rich environment where functional studies can be performed. They facilitate evaluating various approaches including gain and loss of functions and effect of drug treatment, among others. Our preliminary data from the microarray analysis and the validation studies demonstrate that multiple stem cell related genes are strikingly over-expressed in the cancer stroma. Our lab is investigating the functional roles of these genes in ovarian cancer pathogenesis. By employing the 3D model, in addition to animal studies, it will be feasible to reveal the functional roles of these candidate genes on tumor cells in a setting very similar to the disease authentic environment. The understanding of the oncogenic role of these genes in ovarian cancer will provide a novel insight into stromal markers, which will reflect on the strategies for innovative treatment of ovarian cancer. Using advanced molecular and cellular biological techniques to better understand the interplay between epithelial and stromal cells in the tumor microenvironment will provide stronger and more solid bases for future translational and clinical studies related to ovarian cancer treatment.
Selected Publications:
Gagnon A, Kim JH, Schorge JO, Ye B, Liu B, Hasselblatt K, Welch WR, Bandera CA, Mok SC (2008) Use of a combination of approaches to identify and validate relevant tumor-associated antigens and their corresponding autoantibodies in ovarian cancer patients. Clin Cancer Res. 14(3):764-71.
Park DC, Yeo SG, Wilson MR, Yerbury JJ, Kwong J, Welch WR, Choi YK, Birrer MJ, Mok SC, Wong KK (2008) Clusterin interacts with Paclitaxel and confer Paclitaxel resistance in ovarian cancer. Neoplasia. 10(9):964-72. PMCID: PMC2517641.
Aponte M, Jiang W, Lakkis M, Li MJ, Edwards D, Albitar L, Vitonis A, Mok SC, Cramer DW, Ye B (2008) Activation of platelet-activating factor receptor and pleiotropic effects on tyrosine phospho-EGFR/Src?FAK/paxillin in ovarian cancer. Cancer Res 68(14):5839-48.
Callahan MJ, Nagymanyoki Z, Bonome T, Johnson ME, Litkouhi B, Sullivan EH, Hirsch MS, Matulonios UA, Liu J, Birrer MJ, Berkowitz RS, Mok SC (2008) Increased HLA-DMB expression in the tumor epithelium is associated with increased CTL infiltration and improved prognosis in advanced-stage serious ovarian cancer. Clin Cancer Res. 14(23):7667-73.