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Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment
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An update on promising and emerging protein kinase B/AKT inhibitors for breast cancer

Riccardo Asnaghi1,2, Gabriele Antonarelli1,2, Elena Battaiotto1,2

  • 1Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan, Italy.

Expert Opinion on Pharmacotherapy
|January 23, 2025
PubMed
Abstract

Insights

Targeting the PI3K pathway, crucial in breast cancer (BC) and treatment resistance, shows promise. Innovative inhibitors aim to reduce toxicity, improving patient outcomes in HR+ BC therapy.

Area of Science:

  • Oncology
  • Pharmacology

Background:

  • The Phosphatidylinositol 3-Kinase (PI3K) pathway is integral to breast cancer (BC) development, progression, and resistance to therapy, with AKT as a key mediator.
  • Targeting this pathway presents a significant therapeutic opportunity for BC treatment.

Purpose of the Study:

  • To review current and emerging PI3K pathway inhibitors for breast cancer treatment.
  • To highlight innovative strategies for overcoming toxicity and resistance associated with these inhibitors.

Main Methods:

  • Literature review of PI3K pathway inhibitors in breast cancer.
  • Analysis of emerging therapeutic strategies, including selective inhibitors and allosteric modulators.
  • Discussion of advancements in dosing and combination therapies.

Main Results:

  • mTOR inhibitors have advanced treatment for hormone receptor-positive (HR+) BC by addressing endocrine resistance.
  • Toxicity remains a challenge for PIK3CA and AKT inhibitors, necessitating the development of selective agents.
  • Novel allosteric inhibitors and optimized dosing strategies show potential for safer and more effective combination therapies.

Conclusions:

  • Selective PI3K-targeted agents and allosteric inhibitors offer improved safety profiles, potentially enhancing patient adherence and disease management.
  • Advancements in synergistic agents and dosing strategies are crucial for the next phase of AKT-pathway inhibition in HR+ BC treatment.
Keywords:
AKTPI3K-pathwayPIK3CAallosteric inhibitorbreast cancer

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