bims-tumhet 2022-07-10 papers

Issue of 2022–07–10
two papers selected by
Sergio Marchini, Humanitas Research

Cancer Drug Resist. 2022 ;5(2): 451-458

Ovarian cancer recurrence: "is the definition of platinum resistance modified by PARP inhibitors and other intervening treatments?"

Tanja Pejovic, Katherine Fitch, Gordon Mills.

PolyADP ribose polymerase inhibitors (PARPi) have transformed the treatment of ovarian cancer. Particularly in high-grade serous ovarian cancer (HGSOC), a disease characterized by homologous recombination deficiency (HRD), PARPi have had a rapid and profound impact on the disease course, as well as biologic and biomarker definitions of HGSOC, thereby creating a paradigm shift in the approach to treatment. In this review, we discuss the role of PARPi in the maintenance treatment of HGSOC, its effect on platinum sensitivity, and cross-resistance between platinum and PARP inhibitors.

Keywords: PARP inhibitors; maintenance therapy; niraparib; olaparib; ovarian cancer

DOI: https://doi.org/10.20517/cdr.2021.138

Cancer Drug Resist. 2022 ;5(2): 424-435

Ovarian cancer recurrence: is the definition of platinum resistance modified by PARPi and other intervening treatments? The evolving landscape in the management of platinum-resistant ovarian cancer.

Michael J Flynn, Jonathan A Ledermann.

Definitions of platinum resistance have been questioned and changed over the last five years, even though no predictive biomarker of resistance exists. These have sculpted how we approach platinum retreatment and, consequently, how we devise new treatment strategies for those patients with tumour progression on platinum therapy. Platinum-non-eligible ovarian cancer is treated with single-agent non-platinum drugs. When bevacizumab can be added to chemotherapy, progression-free survival improves significantly. For patients with a BRCA mutation, PARP inhibitor monotherapy is an option compared to chemotherapy. There is currently no clearly identified role for immune-checkpoint inhibition in this patient population. This review describes some of the challenges in treating patients with platinum resistance and suggests refinements in the selection of patients most likely to benefit from targeting a DNA damage response, angiogenesis or immune modulation. It also describes novel agents of interest and possible mechanisms of the synergy of therapeutic combinations.

Keywords: DNA damage response; PARP inhibitors; Platinum resistance; VEGF inhibitors; immune checkpoint inhibitors

DOI: https://doi.org/10.20517/cdr.2022.13