Therapeutic agents for targeting desmoplasia: current status and emerging trends

Area of Science:

• Oncology
• Cancer Therapeutics
• Drug Repurposing

Background:

• Desmoplasia, a dense extracellular matrix, hinders chemotherapy efficacy in cancers like pancreatic ductal adenocarcinoma and breast cancer.
• Tumors contain cellular and noncellular components, including chemoresistant cancer stem cells (CSCs) with critical signaling pathways.

Purpose of the Study:

• To review existing and novel therapeutic strategies targeting desmoplasia and cancer stem cells (CSCs).
• To explore the potential of repurposed drugs and new agents as adjuncts to conventional chemotherapy.

Main Methods:

• Literature review of preclinical and clinical studies on antidesmoplastic agents.
• Discussion of repurposed drugs (pentoxifylline, aspirin, metformin) and novel small-molecule, gene, and peptide-based therapeutics.
• Analysis of therapeutic approaches targeting both desmoplasia and CSCs.

Main Results:

• Repurposed drugs like pentoxifylline, aspirin, and metformin demonstrate antidesmoplastic activity.
• Emerging small-molecule, gene, and peptide-based therapies show potential for treating desmoplasia and targeting CSCs.
• Preclinical findings support the evaluation of these agents in ongoing clinical trials.

Conclusions:

• Targeting desmoplasia and CSCs offers a promising strategy to enhance chemotherapy effectiveness.
• Drug repurposing and novel therapeutics represent viable avenues for improving cancer treatment outcomes.
• Clinical trials are crucial for validating the efficacy of antidesmoplastic agents as adjuncts to chemotherapy.