The Interplay between PARP Inhibitors and Immunotherapy in Ovarian Cancer: The Rationale behind a New Combination Therapy

International Journal of Molecular Sciences

Antonio Petracca¹  Gennaro Cormio²  Mauro Francesco Pio Maiorano²  Domenica Lorusso³  Paola Parrella⁴  Evaristo Maiello⁵  Brigida Anna Maiorano⁵  Davide Ciardiello⁵ 

[1] Division of Medical Genetics, Fondazione IRCCS-Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, Italy;Division of Obstetrics and Gynecology, Biomedical and Human Oncological Science, University of Bari “Aldo Moro”, 70121 Bari, Italy;Gynecologic Oncology Unit, Catholic University of the Sacred Heart, Scientific Directorate, Fondazione Policlinico “A. Gemelli” IRCCS, 00168 Rome, Italy;Oncology Laboratory, Foundation Casa Sollievo della Sofferenza IRCCS, San Giovanni Rotondo, 71013 Foggia, Italy;Oncology Unit, Foundation Casa Sollievo Della Sofferenza IRCCS, San Giovanni Rotondo, 71013 Foggia, Italy;

关键词: BRCA;    PARP inhibitors;    HRD;    immune checkpoint inhibitors;    ICIs;    ovarian cancer;   

DOI  :  10.3390/ijms23073871

来源: DOAJ

【 摘 要 】

Ovarian cancer (OC) has a high impact on morbidity and mortality in the female population. Survival is modest after platinum progression. Therefore, the search for new therapeutic strategies is of utmost importance. BRCA mutations and HR-deficiency occur in around 50% of OC, leading to increased response and survival after Poly (ADP-ribose) polymerase inhibitors (PARPis) administration. PARPis represent a breakthrough for OC therapy, with three different agents approved. On the contrary, immune checkpoint inhibitors (ICIs), another breakthrough therapy for many solid tumors, led to modest results in OC, without clinical approvals and even withdrawal of clinical trials. Therefore, combinations aiming to overcome resistance mechanisms have become of great interest. Recently, PARPis have been evidenced to modulate tumor microenvironment at the molecular and cellular level, potentially enhancing ICIs responsiveness. This represents the rationale for the combined administration of PARPis and ICIs. Our review ought to summarize the preclinical and translational features that support the contemporary administration of these two drug classes, the clinical trials conducted so far, and future directions with ongoing studies.

【 授权许可】

Unknown