Therapeutic agents for targeting desmoplasia: current status and emerging trends

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Desmoplasia comprises of cellular and acellular components causing hindrance to chemotherapy. Decreased elasticity and increased interstitial fluid pressure deters drug delivery. Small molecule drugs, genes and peptide therapeutics have potential to target desmoplasia. Ongoing clinical trials on these molecules signify their potential in chemotherapy.

Desmoplasia is a major barrier to chemotherapy in several cancers, particularly pancreatic ductal adenocarcinoma and breast cancer. Tumors comprise of cellular and noncellular components and chemoresistant cancer stem cells (CSCs) with established signaling pathways. In this review, we discuss drugs, such as pentoxifylline, aspirin, and metformin, that have been repurposed and investigated for their antidesmoplastic activity in combination with antitumor drugs. We also highlight less explored new small-molecule drugs, and gene and peptide-based therapeutics for the treatment of desmoplasia and to target CSCs. Promising results from preclinical studies have encouraged several clinical trials to evaluate these antidesmoplastic agents as adjunct to chemotherapy.

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