Chasing Immune Checkpoint Inhibitors in Ovarian Cancer: Novel Combinations and Biomarker Discovery

Abstract

A deep understanding of the tumor microenvironment and the recognition of tumor-infiltrating lymphocytes as a prognostic factor have resulted in major milestones in immunotherapy that have led to therapeutic advances in treating many cancers. Yet, the translation of this knowledge to clinical success for ovarian cancer remains a challenge. The efficacy of immune checkpoint inhibitors as single agents or combined with chemotherapy has been unsatisfactory, leading to the exploration of alternative combination strategies with targeted agents (e.g., poly-ADP-ribose inhibitors (PARP)and angiogenesis inhibitors) and novel immunotherapy approaches. Among the different histological subtypes, clear cell ovarian cancer has shown a higher sensitivity to immunotherapy. A deeper understanding of the mechanism of immune resistance within the context of ovarian cancer and the identification of predictive biomarkers remain central discovery benchmarks to be realized. This will be critical to successfully define the precision use of immune checkpoint inhibitors for the treatment of ovarian cancer.

Targeting the immune microenvironment for ovarian cancer therapy

“…Works by Kandalaft et al. and Colombo and colleagues, focused on the most promising strategies to target the TME considering the immunosuppressive context of OC and the potential future biomarkers ( 280 , 281 ). Finally, Baci and colleagues reviewed the complex innate immune response in the OC TME and how it might either support or limit cancer progression and treatment sensitivity ( 282 ).…”

Advancing Ovarian Cancer Treatment: The Latest Insights on PARP Inhibitors from ASCO 2023

“…ICIs have gained prominence in clinical practice for managing several types of solid tumors; however, their efficacy in OC remains largely poor. 12 For instance, in a recent phase III IMagyn050 trial, the addition of atezolizumab failed to improve the efficacy of platinum-based chemotherapy plus bevacizumab in patients with newly diagnosed stage III/IV OC. 13 Further studies are needed to determine whether alternative drug combinations, including immunotherapy, PARP inhibitors and anti-angiogenic agents, can confer clinical benefits to OC patients.…”

Network-based drug repurposing for HPV-associated cervical cancer

“…Additionally, the US FDA has approved three PD-L1 inhibitors, namely Atezolimumab, Durvalumab, and Avelumab, that have been used in some solid tumors, including cervical cancer [22] . The use of immune checkpoint inhibitors, such as pembrolizumab and dostarlimab, in combination with standard chemotherapy has also shown promising results in recent clinical trials [23] . However, more research is needed to determine the effectiveness of these drugs for cervical cancer therapy.…”