**7. Pharmacogenomics for future predictive marker definition**

Although *BRCA*ness signature definition can provide valuable information regarding the magnitude of the benefit of targeted therapy, these biomarkers may not be unique for the determination of the likelihood of treatment sensitivity/resistance. To date, besides *BRCA* mutations and HRD status, platinum sensitivity remains the best biomarker of PARP inhibitor response. Platinum sensitivity correlates with HRD, and platinum-sensitive tumors are more responsive to PARP inhibitors than platinum-resistant tumors, whatever the genetic background [33, 78]. Therefore, perhaps the PARP inhibitors administration should be offered to all OC patients that respond to platinum-based treatment.

Platinum-based compounds are among the most active and used cytotoxic agents in the clinical practice. They exert their biological effect by acting as alkylating agents by the ability to covalently bind to DNA, leading to the formation of intrastrand and interstrand DNA adducts that promote cell-cycle arrest and tumor cell apoptosis. The mechanisms underlying the development of chemoresistant phenotypes in OC are not fully recognized. Interindividual variation in platinum-drug response might be a major determinant for OC. This is suggested from the wide variability in the PFI and its direct association with a platinum response, as well as the finding that intrinsic resistance to these compounds, occur in up to a fifth of OC patients [106–109]. Mechanisms involved in platinum resistance are likely to be multifactorial although seems to be greatly determined by the platinum detoxification pathway and DNA damage repair ability [54, 108, 110–113].

While platinum therapy is prescribed to achieve a target exposure based on renal function, the dose of taxanes is based on body surface area. Taxanes are microtubule-stabilizing drugs, inducing cell cycle arrest and activating proapoptotic signaling. The cellular toxicity to taxanes is controlled by the action of multiple mediators, namely those involved in transport (i.e., ABCB1, ABCC1, and ABCC2), metabolism, and metabolism-associated proteins (cytochrome P450s and nuclear receptors), as well as pharmacodynamics (i.e., TP53 and CDKN1A), which appear to play a role in taxane efficacy [54, 108, 114–116]. However, to date, no reliable biomarker or signature exists to predict the sensitivity or resistance to paclitaxel. Although the duplet platinum/taxane is associated with better outcome, rather than platinum alone, the results of the GOG132 trial showed that only 42% of patients are likely to benefit from paclitaxel administration [117], and thus, further study into the mechanisms of resistance is needed.
