Author interview: Dr. Nazia Chaudhary is a DST Inspire Faculty in the Cell and Tumor Biology Department at ACTREC, Tata Memorial Centre. She completed her Bachelor’s at Sophia College, her Master’s at St. Xavier’s College, and her Ph.D. at ACTREC. Dr. Chaudhary’s research focuses on therapy resistance and metastasis in colorectal cancer, with particular emphasis on understanding tumor metabolism. Additionally, she is dedicated to developing innovative model systems for studying rare cancer types.
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Research Summary: We developed patient-derived organoid and xenograft models to identify therapeutic vulnerabilities in colorectal signet ring cell carcinoma (SRCC). The findings revealed promising drug combinations that could reduce tumor growth and inhibit peritoneal metastasis.
What was the core problem you aimed to solve with this research? Signet-ring cell carcinoma (SRCC) of the colon and rectum is a rare, aggressive, and therapy-resistant cancer subtype. The lack of a reliable model system has hindered progress in effectively understanding and treating this cancer. Our research aimed to address this challenge by developing patient-derived models to explore drug combinations and uncover the underlying molecular pathways that could be targeted for therapies.
How did you go about solving this problem? Since SRCC is a rare cancer, our study wouldn’t have been possible without the invaluable support of our clinical collaborators, Dr. Saklani and Dr. Kazi, who helped us obtain fresh tumor tissue from patients. We utilized multiple parallel approaches, including tumor collection, performing subcutaneous xenografts in mice, and creating organoid assays. Once the patient-derived organoids (PDO) and patient-derived xenografts (PDX) reached an optimal size, we conducted drug sensitivity assays, RNA sequencing to explore key molecular pathways, and in vivo experiments to assess the safety and efficacy of potential therapeutic strategies.
How would you explain your research outcomes (Key findings) to the non-scientific community? Signet-ring cell carcinoma is a type of cancer that is not only difficult to treat but also spreads rapidly inside the body, causing poor patient survival. Because effective treatments are lacking, part of the challenge is that there has not been a reliable way to study SRCC in the lab. Our study made organoids in the lab using actual patient samples. These organoids are tiny, 3D versions of tumors that closely mimic actual tumors. We also implanted the tumor tissue into mice to create xenografts, this allowed us to study how cancer behaves inside a body. After establishing these models, we tested different drug combinations to determine the most effective ones. Typically, CRC patients are administered drugs like 5-fluorouracil in combination with irinotecan or oxaliplatin, but this does not work for colorectal SRCC. By adding a third drug, we observed significant tumor shrinkage and prevented the tumor from spreading within the body.
The development of these patient-derived models opens new doors for understanding the biology of SRCC and testing more effective treatment strategies, offering hope for better clinical outcomes.” – Dr. Nazia Chaudhary
What are the potential implications of your findings for the field and society? SRCC is an under-researched and rare cancer, but it has a higher occurrence in the Indian population compared to elsewhere in the world, making it a significant area of focus for Indian researchers. Also, the incidence of early-onset cancers is rising; since SRCC is seen mostly in younger patients, it could be that its incidence is increasing globally. Previously, the lack of SRCC model systems made it difficult to test new drugs and study pathways involved in this tumor. Our work, a combined effort of scientists and passionate clinicians who regularly see these types of difficult-to-treat cases, has led to the development of a model to test new drugs. We also provide a basis for new clinical trials to test these more effective treatment combinations for SRCC patients. This research can improve survival rates and the quality of life for affected patients.
What was the exciting moment during your research?
Generating patient-derived organoid and xenograft models from fresh tumor samples was incredibly exciting, which was made possible by the help of our veterinarian. However, discovering that our xenograft models also exhibited a peritoneal metastasis phenotype was the most thrilling part. This is significant because peritoneal metastasis, which worsens patient outcomes, is common in SRCC patients, and modeling it in vivo has been notoriously difficult. To make matters even more exciting, our drug combinations not only reduced the volume of the subcutaneous xenografts but also appeared to eliminate peritoneal metastasis, which was a promising outcome. Moreover, such a complex research problem required the expertise of a diverse group of clinicians—surgeons, oncologists, pathologists, bioinformaticians, basic and translational scientists, as well as a group of young, enthusiastic students. The interactions with them all gave us the enthusiasm and motivation to continue working on this important issue.
Reference: Nazia Chaudhary,et al; Patient-Derived Organoids and Xenografts Uncover Therapeutic Vulnerabilities in Colorectal Signet Ring Cell Carcinomas. Clin Cancer Res 2025; https://doi.org/10.1158/1078-0432.CCR-24-2329
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