In a remarkable breakthrough, Singaporean researchers have successfully grown micro-tumour models outside the human body and used them to identify alternative treatment options for cancer patients who are suffering from resistant or metastatic disease, meaning that they fail to respond to standard-of-care cancer drugs. This innovation will offer hope to the numerous cancer patients grappling with this dreaded disease.
The study has been led by Indian-origin Dr Ramanuj Dasgupta, who is the Group Leader, Cancer Therapeutics and Stratified Oncology at the Genome Institute of Singapore (GIS) of Agency for Science, Technology and Research (A*STAR). The study has also been published in Nature Communications magazine.
This new discovery offers potential to predict treatment response to drugs and help clinicians identify appropriate therapeutic options for cancer patients.
In the study, researchers grew the patients’ own tumour material ex vivo in a dish as ‘micro-tumour avatars’, with the team successfully generating 24 patient-derived avatar-models. These micro-tumour models were then screened for therapeutic and genetic vulnerabilities against a panel of clinically relevant drugs, including standard-of-care treatments such as chemotherapy, radiotherapy or targeted anti-cancer drugs. This approach is known as phenotype-based treatment.
In addition, genomic characterisation of these models helped identify new biomarkers that could predict tumour progression as well as the patients’ response to different classes of drugs.
Among the group of patients involved in the study, two of them went on to receive the phenotype-based treatment in the clinic, and responded remarkably well to the treatment options that were identified, including one where the tumour volume shrank by more than 95 per cent within six weeks of treatment, and the other where the expression of a cancer antigen marker in the blood was reduced by over 90 per cent.
Giving details about the study, Dr Ramanuj Dasgupta, said, “Our approach is unique in the sense that we are using phenotype-driven approaches prospectively to define real-time clinical management of disease, and then investigating the genomic basis for response to identify novel prognostic biomarkers. The ultimate goal would be for this innovative strategy to be available to every cancer patient in future.”
He added, “To truly assess what treatments may or may not work for a given patient, we need to let the patient’s own cancer cells tell us the genetic basis for their response or lack thereof to certain treatments, instead of using historically existing cell lines. This approach would be exceptionally useful where there is a lack of treatment options, for instance in late-stage patients, or a lack of clear biomarker-driven treatment strategies.”
Detailing about the efforts put in for this novel discovery, Dr Gopal Iyer, co-lead author of the study and Senior Consultant Surgical Oncologist at the NCCS ( National Cancer Centre, Singapore), said, “To get this right takes a lot more than just the work reflected in this paper alone. There were years of struggles on both sides to get protocols in place to be able to recruit patients, grow the tumours outside of the patient’s body, testing for genetic and therapeutic vulnerabilities at the screening setup at GIS. and have it run like clockwork, with data analysis in a meaningful manner, making sense of the results, bringing that information back to the hospital for discussions, and finally treating the patient again.
Cancer remains a major cause for disease-related mortality worldwide. It accounted for 8.8 million deaths in 2015; nearly 1 in 6 global deaths was due to cancer. 70 per cent of all cancer deaths afflict people in the developing world, including countries in Africa, Asia, Central and South America.
