Maitham A. Khajah, Princy M. Mathew, Yunus A. Luqmani

Oncology Research, Vol.25, No.8, pp. 1283-1295, 2017, DOI:10.3727/096504017X14883245308282

Abstract Current mainstream pharmacological options for the treatment of endocrine-resistant breast cancer have limitations in terms of their side effect profile and lack of discrimination between normal and cancer cells. In the current study, we assessed the responses of normal breast epithelial cells MCF10A, estrogen receptorpositive (ER+ ) MCF-7, and ER-silenced pII breast cancer cells to inhibitors (either individually or in combination) of downstream signaling molecules. The expression/activity of ERK1/2, p38 MAPK, and Akt was determined by Western blotting. Cell proliferation, motility, and invasion were determined using MTT, wound healing, and Matrigel assays, respectively. Morphological changes… More >

V. Massard, A. Harlé, L. Uwer, J.-L. Merlin

Oncologie, Vol.21, No.1, pp. 29-32, 2019, DOI:10.3166/onco-2019-0027

Abstract Acquired endocrine resistance remains one of the main obstacles in the treatment of estrogen receptor (ER) positive, HER2 negative advanced breast cancer. Recently, activating ESR1 gene mutations affecting the ligand-binding domain have been identified as a key mechanism in aromatase inhibitor (AI) resistance. These mutations can be detected on histological samples or circulating tumour DNA, using PCRbased assays or next-generation sequencing. They induce a constitutive activation of ER, leading to acquired resistance to AI; tamoxifen, fulvestrant and targeted therapies against mTOR or CDK4/6 retain their efficacy. The use of monitoring ESR1 mutations in clinical practice is… More >