Mechanisms of Resistance after 1L CDK4/6i + ET: The PI3K/AKT/PTEN Pathway

Author(s):

Adam M. Brufsky, MD, PhDErika P. Hamilton, MD

Key opinion leaders explore the mechanisms of resistance that can develop after endocrine therapy and CDK4/6 inhibitor treatment in HR+/HER2- breast cancer, emphasizing the uncertain etiology of resistance and current hypotheses, while also examining biomarkers that may predict resistance to CDK4/6 inhibitors and endocrine therapy.

EP: 1.Biomarker Testing Best Practices in HR+/HER2- mBC

EP: 2.First-Line Treatment Options in HR+/HER2- and Challenges with Treatment Resistance

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EP: 3.Mechanisms of Resistance after 1L CDK4/6i + ET: The PI3K/AKT/PTEN Pathway

EP: 4.Clinical Decision Making to Overcome Treatment Resistance in 2L HR+ HER2- mBC

Please provide an overview of the mechanisms of resistance that can emerge following endocrine therapy and CDK4/6 inhibitors in HR+/HER2- breast cancer.
1. What are the major pathways implicated in resistance to ET and CDK4/6i?
Are there any biomarkers that predict resistance to CDK4/6 inhibitors and ET?
1. What other genetic alterations may be implicated in resistance?
Could you discuss the role of the PI3K/AKT/PTEN pathway in driving resistance and progression after first-line treatment with CDK4/6i + ET?
1. In normal cells, what is the role of the PI3K/AKT/PTEN pathway?
2. How might aberrations in PI3K, AKT, or PTEN and dysregulation of this pathway contribute to treatment resistance and progression in HR+/HER2-locally advanced or metastatic breast cancer?
How might alterations in PI3K/AKT/PTEN impact patient outcomes and treatment strategies in HR+/HER2- locally advanced or metastatic breast cancer?
1. Please discuss the frequency of dysregulation in the PI3K/AKT/mTOR pathway in HR+/HER2- locally advanced or metastatic breast cancer patients?