Emerging candidates in breast cancer stem cell maintenance, therapy resistance and relapse

Area of Science:

• Oncology
• Cancer Biology
• Immunology

Background:

• Therapy resistance is a significant challenge in breast cancer treatment, often linked to a subset of cancer cells known as cancer stem cells (CSCs).
• The tumor microenvironment (TME) plays a critical role in sustaining the CSC pool and influencing treatment outcomes.
• Cytokines within the TME act as chemoattractants for leukocytes, modulating CSC behavior and contributing to resistance.

Purpose of the Study:

• To review the emerging role of chemokine receptor and receptor activator of NFκB (RANK) ligand/RANK signaling pathways in breast cancer therapy resistance.
• To elucidate how these pathways contribute to maintaining the cancer stem cell pool within the tumor microenvironment.

Main Methods:

• Literature review synthesizing current evidence on CSCs, TME, and specific signaling pathways in breast cancer.
• Analysis of the interplay between chemokine signaling, RANK ligand/RANK, and CSC maintenance.
• Focus on mechanisms driving therapy resistance and potential therapeutic vulnerabilities.

Main Results:

• Accumulating evidence implicates CSCs as key drivers of therapy resistance and cancer relapse.
• The TME, through secreted signals like cytokines, actively maintains the CSC population.
• Chemokine receptor and RANK ligand/RANK signaling pathways are identified as crucial mediators in this process.

Conclusions:

• Targeting chemokine receptor and RANK ligand/RANK signaling pathways may offer novel strategies to overcome breast cancer therapy resistance.
• Understanding the TME's role in CSC maintenance is essential for developing more effective breast cancer treatments.
• Further research into these pathways could lead to improved patient outcomes by sensitizing tumors to therapy.