Rationale-based therapeutic combinations with PI3K inhibitors in cancer treatment

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• The Phosphatidylinositol 3-Kinase/Protein Kinase B/Mammalian Target of Rapamycin (PI3K/AKT/mTOR) signaling pathway regulates fundamental cellular processes.
• Aberrant PI3K/AKT/mTOR signaling is a hallmark of many cancers, driving uncontrolled cell proliferation, survival, and metabolism.
• Current PI3K inhibitors demonstrate limited efficacy as monotherapies due to intrinsic and acquired resistance mechanisms.

Purpose of the Study:

• To review the PI3K/AKT/mTOR signaling axis and advanced targeted compounds.
• To explore promising rationale-based combination strategies for PI3K/AKT/mTOR inhibitors in solid tumors.
• To emphasize therapeutic combinations in breast cancer treatment.

Main Methods:

• Literature review of PI3K/AKT/mTOR pathway.
• Analysis of current PI3K inhibitors and their limitations.
• Identification and discussion of evidence-based combinatorial therapeutic approaches.

Main Results:

• The PI3K/AKT/mTOR pathway is a critical regulator of cell functions, frequently dysregulated in cancer.
• Monotherapy with PI3K inhibitors often results in insufficient clinical responses.
• Combinatorial strategies are essential for overcoming resistance and maximizing the therapeutic potential of PI3K/AKT/mTOR inhibitors.

Conclusions:

• Targeting the PI3K/AKT/mTOR pathway is a key strategy in cancer therapy.
• Combination therapies involving PI3K/AKT/mTOR inhibitors offer a promising avenue for enhancing antitumor efficacy.
• Further research into rational combinations is crucial for developing effective treatments, particularly for solid tumors like breast cancer.