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Activation of PI3K/AKT/mTOR Pathway Causes Drug Resistance in Breast Cancer

Chao Dong1, Jiao Wu1, Yin Chen2

  • 1Department of the Second Medical Oncology, The 3rd Affiliated Hospital of Kunming Medical University, Yunnan Tumor Hospital, Kunming, China.

Frontiers in Pharmacology
|April 1, 2021
PubMed

Insights

Acquired resistance to breast cancer therapies like chemotherapy is common. Targeting the PI3K/AKT/mTOR pathway shows promise in overcoming this resistance, improving treatment outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Standard breast cancer treatments (chemotherapy, targeted, endocrine therapy) often face acquired drug resistance.
  • The phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway is frequently hyperactivated in resistant cancers.
  • This pathway activation correlates with disease progression and treatment failure in breast cancer.

Purpose of the Study:

  • To review the role of the PI3K/AKT/mTOR pathway in acquired drug resistance in breast cancer.
  • To discuss the development of inhibitors targeting the PI3K/AKT/mTOR pathway.
  • To explore strategies for overcoming acquired resistance using these inhibitors in combination with standard therapies.

Main Methods:

  • Literature review of preclinical and clinical studies.
  • Analysis of research on PI3K/AKT/mTOR pathway signaling in breast cancer.
  • Synthesis of data on PI3K/AKT/mTOR inhibitors and combination therapy strategies.

Main Results:

  • The PI3K/AKT/mTOR pathway is a key mediator of resistance to multiple breast cancer therapies.
  • Numerous PI3K/AKT/mTOR inhibitors are in various stages of clinical development.
  • Combination strategies involving PI3K/AKT/mTOR inhibitors and standard treatments are being actively investigated.

Conclusions:

  • The PI3K/AKT/mTOR pathway is a critical target for overcoming acquired resistance in breast cancer.
  • Targeting this pathway offers a promising approach to enhance the efficacy of existing breast cancer treatments.
  • Further clinical investigation is essential to establish the optimal use of PI3K/AKT/mTOR inhibitors in breast cancer therapy.
Keywords:
PI3Kchemotherapydrug resistanceendocrine therapytargeted therapy

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