The existing current classification of ovarian epithelial malignancies is based on descriptive histopathology and grading of the degree of differentiation. Using this approach the disease is broken out into six major classes as follows: Borderline malignancies, clear cell carcinomas, mixed mullerian tumors (MMT), mucinous adenocarcinomas, endometrioid adenocarcinomas, and papillary serous carcinomas (most common form constituting more than 80% of the cases). There are obvious differences in the traditional pathologic classifications of the various ovarian epithelial cancers based on their histologic appearance. There is also variability in recurrence rates depending on the histologic subtype. Despite this, all of these cancers are treated in the same manner outlined below. While the descriptive pathology can be helpful in assigning some prognostic information, it tells us little about what might be “driving” the underlying pathogenesis of the disease. Little is known about the molecular pathogenesis of these ovarian cancer subtypes.
Within the UCLA Translational Cancer Research Laboratories at the Jonsson Comprehensive Cancer Center (JCCC) at UCLA we are attempting to better understand the genetic causes and molecular drivers of ovarian cancer. To this end, we have accessed large cohorts of clinical ovarian lesions that are annotated with clinical and demographic information. These lesions have been carefully molecularly characterized and we have been able to identified 4 new distinct molecular subgroups in ovarian cancer with very distinct dominant signaling pathways and signaling alterations. This information is being used to identify, develop and test novel and innovative approaches for the treatment of ovarian cancers. Broad preclinical testing of a growing number of directed inhibitors is being performed in parallel in the UCLA Translational Oncology Research Laboratory in Santa Monica using reliable preclinical ovarian cancer models. The initial “proof of concept” clinical trials are being conducted in the TRIO US clinical research network. With the large number of targeted therapies now in development, rational approaches for deciding which of the new therapies to test in clinic in which molecular ovarian cancer subtype and which ones to use in which combination are urgently needed. Our laboratory and clinical work has helped to develop promising novel treatment rationales are currently undergoing clinical validation in trials conducted within the existing TRIO US and Global clinical research networks.