Opinion How scientists developed a new way of examining a rare form of colorectal cancer
CRCs are the third most common cancer and the second leading cause of cancer deaths in the world. However, SRCC is an uncommon variant of CRC. Globally, this type of cancer constitutes about 1% of all cases of CRC.
The study has uncovered unique molecular features of SRCC that help explain why it does not respond to traditional chemotherapy. 
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A team of scientists 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. SRCC, which gets its name from the signet ring-like appearance (a finger ring with a flat top) of its cancer cells under a microscope, is one of the deadliest subtypes of colon cancer. It spreads quickly, resists conventional therapies, and is often diagnosed at advanced stages.
One of the biggest challenges in treating SRCC has been the cancer’s tendency to spread to the peritoneum — the lining of the abdominal cavity — which is a key reason for its poor prognosis. The new methods developed by the scientists for analysing SRCC have given hope for overcoming this issue.
The details of the findings were described in a study, ‘Patient-Derived Organoids and Xenografts Uncover Therapeutic Vulnerabilities in Colorectal Signet Ring Cell Carcinomas’, which was published in the journal Clinical Cancer Research on April 1.
The study was led by Nazia Chaudhary, a researcher at the Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre (Navi Mumbai). Her team included surgeons A Saklani and M Kazi, oncologist Vikas Ostwal, pathologists Poonam Gera and Munita Bal, translational and basic scientists Lalit Sehgal, Alessandro La Ferlita, Nandini Verma, and Sorab N Dalal, veterinarian Rahul Thorat, and a team of students.
How common is signet ring cell carcinoma (SRCC) in India?
CRCs are the third most common cancer and the second leading cause of cancer deaths in the world. However, SRCC is an uncommon variant of CRC. Globally, this type of cancer constitutes about 1% of all cases of CRC.
However, “in countries like India, SRCC appears to affect a disproportionately 10 times larger number of patients, often younger individuals, and has been notoriously difficult to treat due to its spread in the peritoneal cavity [the space within the abdomen that contains the intestines, the stomach, and the liver],” Chaudhary told The Indian Express.
A recent study found that central and northern India had the highest proportion of SRCC cases in the country.
What are the findings of the study?
Chaudhary and her team have introduced an innovative method to analyse SRCC. They have created patient-derived organoids (PDOs) and patient-derived xenografts (PDXs). Put simply, they are miniaturised models of real human SRCC tumours that have been grown in lab petri dishes and implanted into mice.
As these models mimic the molecular behaviour of real human SRCC tumours, they offer scientists an opportunity to examine cancer closely and test potential treatments in a controlled environment, according to the study. “This is one of the first living biobanks of SRCC models,” said Chaudhary.
The study has uncovered unique molecular features of SRCC that help explain why it does not respond to traditional chemotherapy. By analysing the PDO and PDX models, the research team was able to test a wide range of drug combinations to find therapeutic vulnerabilities — specific weak spots that could be exploited with targeted treatments.
One of the study’s most promising results came from testing a novel three-drug combination that not only shrank tumours but also curbed the cancer’s spread in lab models. “These findings could pave the way for future clinical trials and, potentially, new treatment options for cancer,” said Chaudhary. Phase 1 clinical trials are required for further investigation.
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