Context:

A new study from the Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, has developed new ways to better understand and treat signet ring cell carcinoma (SRCC), a rare form of colorectal cancer (CRC), which starts in the colon or rectum. The study was published in Clinical Cancer Research and involved collaboration between oncologists, surgeons, pathologists, translational scientists, and students.

Understanding Signet Ring Cell Carcinoma (SRCC)

Signet Ring Cell Carcinoma (SRCC) is a rare and aggressive subtype of colorectal cancer (CRC), known for its distinct signet ring-like appearance under a microscope. It is typically diagnosed at advanced stages and shows resistance to conventional therapies.

·        One of the major concerns is its rapid spread to the peritoneum, the lining of the abdominal cavity, which significantly worsens patient outcomes.

·        Globally, SRCC accounts for only about 1% of all CRC cases. However, in India, particularly in central and northern regions, this figure is disproportionately higher—almost 10 times more.

·        Strikingly, it tends to affect younger individuals, and due to its rapid spread within the abdominal cavity, it has been particularly difficult to treat effectively using traditional approaches.

Key Findings and Drug Testing

The study introduced Patient-Derived Organoids (PDOs) and Patient-Derived Xenografts (PDXs) as tools to model human SRCC tumours.

·        PDOs are miniaturised 3D versions of human tumours grown in petri dishes, while PDXs involve transplanting human cancer cells into mice. These models replicate the molecular characteristics of SRCC, allowing researchers to analyse the cancer’s behaviour and response to treatments more effectively.

·        Using these models, the researchers identified molecular features that explain why SRCC does not respond to standard chemotherapy.

·        They were able to test multiple drug combinations and discovered a novel three-drug regimen that significantly reduced tumour growth and inhibited metastasis in preclinical trials. This opens up the possibility for future clinical trials and more effective, targeted treatments.

Conclusion

Described as one of the first living biobanks for SRCC, this research provides a vital foundation for personalised medicine and drug development. It offers hope for improved treatment outcomes, particularly for patients in India where SRCC incidence is notably higher. Phase 1 clinical trials will be necessary to validate these findings and develop real-world therapies.