Targeting PI3K signaling in Lung Cancer: advances, challenges and therapeutic opportunities

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Lung cancer is a leading global cause of mortality, driving the search for novel therapeutic targets.
• The phosphoinositide 3-kinase (PI3K) signaling pathway is integral to cancer development, regulating cell growth, survival, metabolism, and immune responses.

Purpose of the Study:

• To review the specific roles of PI3K subtypes (PI3Kα, PI3Kβ, PI3Kγ, PI3Kδ) in lung cancer.
• To evaluate current PI3K inhibitors, their efficacy, resistance mechanisms, and combination strategies.
• To explore the PI3K pathway's interaction with the tumor immune microenvironment and metabolic reprogramming.

Main Methods:

• Comprehensive literature review of PI3K signaling in lung cancer.
• Analysis of PI3K inhibitor development, from non-selective to isoform-specific agents.
• Examination of preclinical and clinical data on PI3K-targeted therapies and their impact on tumor immunity and metabolism.

Main Results:

• PI3K pathway dysregulation is implicated in lung cancer pathogenesis and progression across its subtypes.
• PI3K inhibitors show promise but face challenges including resistance and side effects.
• Modulating PI3K signaling can enhance anti-tumor immunity and exploit metabolic vulnerabilities.

Conclusions:

• The PI3K pathway is a critical and multifaceted target in lung cancer.
• Personalized medicine approaches and next-generation inhibitors are needed to overcome resistance and improve outcomes.
• Integrated strategies targeting PI3K signaling hold significant therapeutic potential for lung cancer patients.