Triple Negative Breast Cancer: A Mountain Yet to Be Scaled Despite the Triumphs

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Triple-negative breast cancer (TNBC) is the most aggressive subtype, associated with lower survival rates and high mortality due to metastatic progression and recurrence.
• Chemotherapy is the primary treatment, but chemoresistance significantly limits its efficacy, leading to treatment failure.

Purpose of the Study:

• To review the current understanding of mechanisms driving TNBC chemoresistance, metastasis, and tumor relapse.
• To discuss the approved standard of care and identify targetable molecular mechanisms for TNBC management.
• To provide an update on recent advancements in TNBC treatment strategies.

Main Methods:

• This review synthesizes existing literature on TNBC, focusing on chemoresistance.
• It examines the roles of ABC transporters, DNA damage response genes, cancer stem cells, and metabolic reprogramming.
• The review analyzes current treatment standards and emerging therapeutic targets.

Main Results:

• Chemoresistance in TNBC is multifactorial, involving the activation of ABC transporters and DNA damage response pathways.
• Enrichment of cancer stem cells and metabolic reprogramming are key contributors to the selection of resistant cell populations.
• These chemoresistant cells are implicated in distant metastasis and subsequent tumor relapse.

Conclusions:

• Elucidating the molecular mechanisms of TNBC chemoresistance is critical for overcoming treatment failures.
• Targeting identified pathways and leveraging recent advancements may improve outcomes for TNBC patients.
• Further research into TNBC biology is essential for developing more effective therapeutic strategies.