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. Author manuscript; available in PMC: 2023 Nov 27.
Published in final edited form as: Oncogene. 2022 Jun 9;41(27):3524–3538. doi: 10.1038/s41388-022-02362-2

Fig. 7. Scheme illustrating the function of RB loss.

Fig. 7

Endocrine therapy, CDK4/6, and PI3K/mTOR inhibitors impact cyclin D1/CDK4/6 function thereby activating RB to induce cell cycle arrest. Loss of RB results in sustained E2F activity even in the presence of cytostatic drugs that transactivates cyclin E to drive cell cycle via CDK2 activity. Alisertib in combination with MK1775 induces apoptosis selectively in RB-deficient setting. Birinapant, an inhibitor of IAP, which is an anti-apoptotic protein results in enhanced apoptotic mediated cell death in RB -deficient ER + breast cancer models. Overall, RB loss leads to therapeutic resistance to the standard cytostatic treatment options and becomes more vulnerable to pharmacological agents that induce apoptosis.