The PI3K Pathway: Background and Treatment Approaches
Michael P Lux1, Peter A Fasching1, Michael G Schrauder1
1University Breast Center for Franconia, Department of Gynecology, Erlangen University Hospital, CCC Erlangen-EMN, Erlangen, Germany.
Breast Care (Basel, Switzerland)
|February 24, 2017
Summary
Hormone receptor-positive metastatic breast cancer often becomes resistant to endocrine therapy. The PI3K/Akt/mTOR pathway is crucial in resistance, and PI3K inhibitors show promise for overcoming it.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Two-thirds of metastatic breast cancers are hormone receptor (HR)-positive/HER2-negative.
- Endocrine therapy is a primary treatment, but resistance (primary and secondary) is common.
- The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is frequently implicated in breast cancer and endocrine resistance.
Purpose of the Study:
- To explore the role of the PI3K/Akt/mTOR pathway in endocrine resistance in breast cancer.
- To investigate the potential of PI3K inhibitors as a therapeutic strategy for overcoming endocrine resistance.
Main Methods:
- Review of current literature on HR+/HER2- metastatic breast cancer treatment and endocrine resistance mechanisms.
- Analysis of the PI3K/Akt/mTOR signaling pathway's involvement in resistance development.
- Evaluation of preclinical and early clinical data on PI3K inhibitors.
Main Results:
- Tamoxifen resistance affects a significant proportion of patients with metastatic breast cancer.
- The PI3K/Akt/mTOR pathway is a key player in the development of both primary and secondary endocrine resistance.
- Mutations within this pathway are frequent in breast cancer, though their full prognostic significance is under investigation.
- PI3K inhibitors demonstrate promising therapeutic potential with a manageable side effect profile in initial studies.
Conclusions:
- Understanding endocrine resistance mechanisms, particularly involving the PI3K/Akt/mTOR pathway, is critical for improving treatment outcomes.
- Targeting the PI3K/Akt/mTOR pathway with inhibitors represents a promising strategy to overcome endocrine resistance in HR+/HER2- metastatic breast cancer.
- Further research into PI3K pathway mutations may aid in patient selection for targeted therapies.
Keywords:
Breast cancerEndocrine resistanceEstrogen receptorPI3KPIK3CAPhosphatidylinositol 3-kinasePhosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alphaMore Related Videos
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