paywalled- Low-Grade Serous Carcinoma: New Concepts and Emerging Therapies

Abstract

Review

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Highlights

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Low-grade serous carcinoma is characterized by relative chemoresistance and prolonged survival.

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The MAP kinase signaling pathway is an important target for low-grade serous carcinoma.

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For the past several  years (Blogger's Note: several years or decades??), all women with epithelial ovarian cancer have been treated identically, whether in a clinical trial or off protocol. Over the past decade, we have come to appreciate the magnitude of the heterogeneity of ovarian cancer. The development of the binary grading system for serous carcinoma was a major advance leading to separate clinical trials for patients with this subtype originating from the Gynecologic Oncology Group’s Rare Tumor Committee. The mitogen-activated protein kinase (MAPK) pathway appears to play a prominent role in the pathogenesis of this subtype. Approximately 20-40% of low-grade serous carcinomas have a KRAS mutation, while BRAF mutations are rare—about 5%. Primary treatment of low-grade serous carcinoma includes surgery + platinum-based chemotherapy (either adjuvant or neoadjuvant). Clinical behavior is characterized by young age at diagnosis, relative chemoresistance, and prolonger overall survival. Current options for treatment of relapsed disease include secondary cytoreduction in selected patients, salvage chemotherapy, or hormonal therapy. A recently completed trial of a MEK inhibitor for women with recurrent disease demonstrated promising activity. Future directions will include further investigations of the molecular biology and biomarker-driven clinical trials with targeted agent monotherapy and combinations.

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MEK inhibitor

From Wikipedia, the free encyclopedia

A MEK inhibitor is a chemical or drug that inhibits the mitogen-activated protein kinase kinase enzymes MEK1 and/or MEK2. They can be used to affect the MAPK/ERK pathway which is often overactive in some cancers. (See MAPK/ERK pathway#Clinical significance.)
Hence MEK inhibitors have potential for treatment of some cancers,^[1] especially BRAF-mutated melanoma,^[2] and KRAS/BRAF mutated colorectal cancer.^[3]

Some MEK inhibitors:

• Trametinib (GSK1120212), studied in BRAF-mutated melanoma
• Selumetinib, had a phase 2 clinical trial for non-small cell lung cancer (NSCLC)
• MEK162, had phase 1 trial for biliary tract cancer and melanoma^[4]
• PD-325901, for breast cancer, colon cancer, and melanoma^[5]
• XL518, CI-1040, PD035901