Tumor under forces: biophysical remodeling of tumor microenvironment and associated therapeutic opportunities.

Authors

Rashmita Luha, Gomathi Sankar, Siddhesh Saigaonkar, Suseel Mathusoothanan, Ajay Tijore

Published in

Seminars in cancer biology. Pages 102634. Oct 16, 2026. Epub Oct 16, 2026.

Abstract

Tumors progress within a mechanically dynamic tumor microenvironment (TME), where extracellular matrix (ECM) stiffening, solid stress, and elevated interstitial fluid pressure remodel tumor cell and tumor-associated cell behavior. This TME-related mechanical remodeling often leads to tumor progression, metastasis and therapy resistance. In this review, we highlight recent advances in tumor mechanobiology, emphasizing how biophysical forces generated by cross-talk between tumor cells and tumor-associated cells precisely drive TME remodeling-ECM stiffening, hypoxia, leaky vasculature, invasion and therapy resistance-to support cancer progression. We discuss emerging interventions for selective tumor targeting that exploit the mechanical properties of the TME and biomechanical vulnerabilities of tumors and tumor-associated cells. Finally, this review explores the potential to leverage mechanobiological insights into the TME using New Approach Methodologies (NAMs), such as 3D bioprinted models and organ-on-chip platforms, coupled with AI-powered image analysis and modeling, to enable personalized cancer diagnosis and treatment.

PMID:
42887575
Bibliographic data and abstract were imported from PubMed on 17 Oct 2026.

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