From molecular insight to therapeutic strategy: The holistic approach for treating triple negative breast cancer

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Triple-negative breast cancer (TNBC) is an aggressive subtype with limited targeted therapies.
• TNBC exhibits molecular heterogeneity, necessitating subtype-specific treatment strategies.
• Understanding TNBC's molecular pathogenesis is crucial for developing effective therapeutic approaches.

Purpose of the Study:

• To analyze the molecular pathogenesis of TNBC.
• To evaluate current therapeutic practices, challenges, and future treatment goals.
• To categorize TNBC subtypes based on pathway alterations and predict drug susceptibility.

Main Methods:

• Categorization of TNBC subtypes (Lehmann's subgroups) based on distinct pathway alterations.
• Meta-analysis of 12 randomized clinical trials involving various drug regimens.
• Evaluation of drug efficacy as monotherapy versus combination therapy.

Main Results:

• Basal-like 1 (BL1) and Basal-like 2 (BL2) TNBC subtypes are susceptible to DNA intercalating drugs.
• Mesenchymal (M) and mesenchymal stem-like (MSL) subtypes require targeted therapies for upregulated signaling and survival pathways.
• Combination therapy of DNA destabilizers and angiogenesis inhibitors showed significantly higher efficacy (OR: 5.011-7.286) compared to monotherapy, suggesting prevalence of BL1 TNBC.

Conclusions:

• Personalized medicine, tailored to specific TNBC molecular subtypes, is essential for optimizing treatment outcomes.
• Combination therapies, particularly DNA destabilizers with angiogenesis inhibitors, demonstrate superior efficacy in certain TNBC populations.
• Further research into targeted therapies for mesenchymal and immunomodulatory TNBC subtypes is warranted.