The Genetic Secret That Could Transform Ovarian Cancer Treatment

PPP2R1A is a key predictive biomarker and potential treatment target across multiple cancer types.

Researchers have discovered that patients with ovarian clear cell carcinoma (OCCC) who carry certain mutations in the PPP2R1A gene respond more favorably to immunotherapy.

These patients experienced better survival outcomes than those whose tumors lacked the mutation, highlighting the potential of genetic profiling to guide more effective, personalized treatment strategies for OCCC ().

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Ovarian clear cell carcinoma is tough to treat, but new hope emerges! Patients with specific PPP2R1A mutations in their tumors showed longer survival after immunotherapy. #OvarianCancer #Immunotherapy #ClearCellCarcinoma

The findings, published in Nature, suggest PPP2R1A mutations could be a valuable biomarker to help guide treatment for this difficult-to-treat ovarian cancer subtype and may offer a new therapeutic target to further improve outcomes in multiple cancer types.

Results of the study found that patients with PPP2R1A-mutant OCCC had a median overall survival (OS) of more than five years (66.9 months) after immunotherapy treatment, compared to just 9.2 months for patients without this mutation.

PPP2R1A Mutations Show Broad Impact on Immunotherapy Outcomes Across Cancers

“Developing effective immunotherapies for ovarian cancer, including rare subtypes like ovarian clear cell carcinoma, remains a significant unmet clinical need,” said co-senior author Amir Jazaeri, M.D., professor of Gynecologic Oncology and Reproductive Medicine. “Our study is the first to demonstrate the clinical importance of PPP2R1A mutations, and it opens the door to new strategies that could benefit many more patients.”

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In a Phase II trial, researchers investigated outcomes in a cohort of 34 patients with treatment-resistant OCCC who had been treated with a combination of immune checkpoint inhibitors – durvalumab and tremelimumab.

Based on their findings in OCCC, experts also looked at two additional independent cohorts, one consisting of patients with endometrial cancer and the other including more than 9,000 patients with multiple cancer types who received immunotherapy treatment. Analyses confirmed the improved OS following immunotherapy in those with tumor PPP2R1A mutations.

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Lab Studies Confirm PPP2R1A Targeting Boosts Immunotherapy Response

In parallel, laboratory research showed that targeting PPP2R1A both in vitro and in vivo was also associated with improved response to immunotherapy, suggesting a causal link. This too indicates that therapies targeting PPP2R1A and the associated protein phosphatase 2A (PP2A) molecular pathway could be added to immunotherapy to further boost outcomes.

“Not only did we identify a new biomarker in ovarian cancer, but we also confirmed survival benefits in other cancer types,” Jazaeri said.

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“Since PPP2R1A mutations are relatively uncommon, we believe the same benefits may be possible by targeting the PPP2A pathway --using drugs, and we currently are evaluating this in a clinical trial at MD Anderson.”

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