ESR1 and neoplasm: Several molecular resistance mechanisms were proposed, which include alterations in the estrogen receptor (ER) expression, ESR1 mutations, altered expression of growth factor receptors, the activation of the PI3K/Akt/mTOR pathway, dysregulation of ER co-activators, altered expression of cell cycle regulators, autophagy, epithelial to mesenchymal transition, and increased tumor heterogeneity [3,4].