Research Summary: Ultrasound-generated mechanical forces selectively induce apoptosis in patient-derived oral cancer-associated fibroblasts by targeting their altered mechano-sensitivity without harming normal fibroblasts, offering a non-invasive approach to target tumor stroma.
Author interview
Gomathi Sankar is a PhD student in Dr Ajay Tijore’s Lab, Indian Institute of Science. His research explores the potential of ultrasound-mediated mechanical forces to disrupt the tumor stroma by targeting cancer-associated fibroblasts for oral cancer treatment.
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Lab: Dr Ajay Tijore, Indian Institute of Science Bangalore
What was the core problem you aimed to solve with this research?
Tumor stroma, especially cancer-associated fibroblasts (CAFs), plays a major role in cancer progression and therapy resistance. These activated fibroblasts remodel the extracellular matrix, secrete chemokines, and create a stiff and protective environment that shields tumor cells. Our work aimed to develop a non-invasive mechanical approach using ultrasound to selectively eliminate these CAFs without affecting normal fibroblasts, disrupting the tumor microenvironment.
How did you go about solving this problem?
To develop this novel treatment method for oral cancer, we used a mechanobiology-driven approach to target patient-derived oral CAFs. We designed experiments with a custom-built low-frequency ultrasound setup capable of generating physiologically relevant mechanical forces without causing thermal-based tissue damage.
Through a combination of live-cell imaging, immunofluorescence and biochemical assays, we discovered that ultrasound selectively induced mechanoptosis (mechanical force mediated cell killing) in CAFs while sparing normal fibroblasts. Further mechanistic studies revealed that this selectivity arises from the loss of key mechanosensory cytoskeletal protein Tropomyosin2.1(Tpm2.1) driven by cancer-cell secreted microRNA-21(miR-21). This mechanical vulnerability made CAFs uniquely sensitive to ultrasound treatment.
How would you explain your research outcomes (Key findings) to the non-scientific community?
CAFs are activated fibroblasts in tumor environment that build a stiff, protective environment around tumors, making treatments less effective. Our study shows how low-frequency ultrasound can be used to selectively eliminate these supporting fibroblasts that support cancer growth without harming normal cells.
Our work demonstrates how mechanical forces from ultrasound can selectively target cancer’s supportive fibroblasts, offering a safe, non-invasive therapeutic strategy. — Dr. Ajay Tijore
What are the potential implications of your findings for the field and society?
Our findings open a new direction in cancer therapy, a mechanobiology-based, non-invasive, selective method to target tumor stroma. By selectively eliminating cancer-associated fibroblasts, ultrasound can help dismantle the stromal shield that promotes tumor growth, metastasis, and drug resistance. Beyond oral cancer, this strategy could be extended to other solid tumors rich in fibroblasts. Clinically, it could lead to more precise, patient-friendly treatments that target cancer’s supportive ecosystem rather than only the tumor cells themselves.
What was the exciting moment during your research?
The most exciting moment came when we observed that ultrasound could selectively kill oral cancer patient-derived CAFs while leaving normal fibroblasts untouched. It proved that ultrasound waves alone, could distinguish between normal and tumor-supporting cells purely based on their mechanical properties. What made it even more exciting was that our entire research used CAFs isolated directly from oral cancer patients, allowing us to account for the natural heterogeneity among samples. Seeing consistent mechanoptosis across diverse patient-derived CAFs strongly validated our approach and revealed the translational promise of ultrasound-based targeting in real tumor conditions.
Paper reference: Gomathi Sankar, Arka Roy Choudhury, Rashmita Luha, Akshay Kumar, Ketan Kulkarni, Mingxi Yao, Rudra Pratap, Aravind Kapali, Ajay Tijore, Selective killing of cancer-associated fibroblasts by ultrasound-mediated mechanical forces, Biomaterials, Volume 328, 2026, 123844, ISSN 0142-9612, https://doi.org/10.1016/j.biomaterials.2025.123844.
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