Ovarian cancer molecular stratification and tumour heterogeneity; a necessity and a challenge (serous)

Opinion - open access

 Introduction

Only two new drugs have been licensed for the treatment of epithelial ovarian cancer in the last 5 years (bevacizumab and olaparib). These are also the only two molecularly-targeted agents licensed in this disease. As we continue to move into the genomic era of cancer therapy, it is clear that optimal therapy is going to depend on molecular stratification and that the stratification itself is going to need to contend with tumour heterogeneity. In this article, we discuss molecular stratification and tumour heterogeneity in the context of high grade serous ovarian cancer.

The development of bevacizumab and olaparib have provided contrasting examples of stratification in molecularly targeted agents.....

 The future

Clearly future optimal therapy for high-grade serous ovarian cancer will depend on optimal molecular stratification and this is just as true for bevacizumab and olaparib as it will be for future agents. While this will help rise to the challenge of optimising therapy for inter-patient molecular heterogeneity, monotherapy may never overcome intra-patient heterogeneity. If we want to improve the durability of responses, that pool of resistant clones may need to be narrowed by using combination therapies. Indeed, recent clinical data for the addition of the VEGFR inhibitor, cedirinib, to olaparib has shown a significant increase in response rate and a near-doubling of progression free survival [47]. The majority of this benefit was in the BRCA1/BRCA2 wild-type (or unknown) group, perhaps demonstrating that combinations can overcome monotherapy dependencies but also highlighting that there is still a lot to learn about biomarkers for anti-angiogenic and PARP inhibitor agents in ovarian cancer.