Abstract TF1-2: ER+ word salad decoded: SERD, SERM, SERCA, CERAN, PROTAC

Abstract

Abstract Estrogen receptor (ER) plays an important role in gene transcription and the proliferation of ER positive (ER+) breast cancers. Selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs) and fulvestrant, a selective estrogen receptor degrader (SERD) are currently approved therapeutic approaches for ER positive breast cancers. While these treatment strategies are highly effective, de novo and secondary resistance remains a challenge. Despite resistance mechanisms including due to mutations in the ligand binding domain of the ERα gene (ESR1 mutations), ER+ breast cancers continue to rely on receptor activity for growth signaling, underscoring the need for more effective treatments. To overcome the limitations of the existing endocrine therapies, there has been a quest to develop more potent and selective ER antagonists by altering aspects of drug binding or induction of proteolytic degradation of the receptor through different mechanisms. These orally bioavailable agents offer the potential for low toxicity and improved activity and are in various phases of clinical development either as monotherapy or in combination with targeted therapies. Citation Format: K Jhaveri. ER+ word salad decoded: SERD, SERM, SERCA, CERAN, PROTAC [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr TF1-2.