- A study by clinician-scientists at the National Cancer Centre Singapore has found a link to cancer in a silent mutation commonly assumed to be insignificant
- First-in-the-world study to link a non-coding RNA to a targeted treatment
- Findings from this study may open up novel avenue options for patients with cancers affecting the head & neck and/or lung
Singapore, 16th November 2017 – A recent study by clinician-scientists at the National Cancer Centre Singapore (NCCS) has made a breakthrough discovery on how a silent mutation, which has been commonly disregarded in prevailing cancer studies, actually plays a key role in cancer, specifically a type of head and neck and lung cancer called squamous cell cancer.
The findings from this groundbreaking study, is expected to help enhance treatment in these cancers by identifying patients that would benefit from readily available, targeted drugs that were not earlier recommended in the treatment regime. The discovery was jointly led by co-Principal Investigators, Associate Professor Gopal Iyer, Senior Consultant Surgical Oncologist and Dr Daniel Tan, Senior Consultant Medical Oncologist, both at NCCS.
Based on research primarily performed in an on-site laboratory at NCCS over the course of four years, the findings were recently published in Nature Medicine, a leading and prestigious international scientific and medical journal, reflecting the significance and high impact of the study.
Traditionally, scientists focus their attention on non-synonymous mutations, which change the protein sequence and function, eventually leading to cancer. Silent mutations, or synonymous mutations, were assumed insignificant since they have no consequences in the protein sequence.
Through a previous study by NCCS on head and neck squamous cell carcinoma, two out of 40 patients had an exceptional response to a targeted drug called gefitinib, which is traditionally used for lung cancer. Silent mutations were identified in both patients and researchers did not understand why they responded.
Independently, lab findings showed a similar scenario where cells derived from patients with the same synonymous mutations were also extremely sensitive to gefitinib, a drug that targets a protein called epidermal growth factor receptor (EGFR). The coincidence here motivated A/Prof Iyer and Dr Tan’s team at the Cancer Therapeutic Research Laboratory to pursue this particular silent mutation in the EGFR gene.
They were surprised to find that although silent mutations do not directly change the protein sequence of EGFR, they actually influence the level of a long non-coding RNA named EGFR-AS1 (Figure 1). Long non-coding RNAs are a recently discovered class of RNA molecules whose functions are not well-understood and never previously implicated in response to drugs. The mutation here changed the way cancer cells processed EGFR, affecting how gefitinib killed these cells. Based on these results, doctors at NCCS treated another 7 patients with the same silent mutations with good outcomes.
“We are very excited to share the findings of this study with the medical and research community. The findings bring new possibilities and reflect a paradigm shift,” said Dr Tan. “This study may open up new drug avenues. There have been many approved EGFR targeted drug in the market. If we can measure the expression of long non-coding RNA in the appropriate context, we can potentially identify patients who can benefit from the existing drugs.” Dr Tan is also an Adjunct Associate Professor at Duke-NUS, Oncology Academic Clinical Programme (ACP).
“We are fortunate to have leading-edge medical facilities and infrastructural support for research in NCCS and with the scientific community in Singapore. NCCS has provided invaluable support for us to conduct these experiments: we have fantastic on-site lab facilities, patient-derived materials and the support of the Experimental Cancer Therapeutics Research Unit (ECRU) at NCCS, where clinicians are excited about and willing to put their patients into this study. Philanthropic grants provided by NCC Research Funds have also enabled us to perform high risk experiments like this,” said A/Prof Iyer.
A/Prof Iyer is also Associate Professor at Duke-NUS, Oncology Academic Clinical Programme (ACP), and Cancer & Stem Cell Biology Programme.
A/Prof Iyer and Dr Tan hope to pursue this novel concept in larger patient cohort. They are exploring the development of trials in collaboration with pharmaceuticals to extend these findings and extend the study to other cancer types. They will also be developing diagnostic kits at NCCS to identify patients with these silent mutations.
About National Cancer Centre Singapore
National Cancer Centre Singapore (NCCS) provides a holistic and multi-disciplinary approach to cancer treatment and patient care. We treat almost 70 per cent of the public sector oncology cases, and they are benefiting from the sub-specialisation of our clinical oncologists. NCCS is also accredited by the US-based Joint Commission International for its quality patient care and safety. To deliver among the best in cancer treatment and care, our clinicians work closely with our scientists who conduct robust cutting-edge clinical and translational research programmes which are internationally recognised. NCCS strives to be a global leading cancer centre, and shares its expertise and knowledge by offering training to local and overseas medical professionals. www.nccs.com.sg
For more information, please contact:
National Cancer Centre Singapore
Ms Rachel Tan
Manager, Corporate Communications
Office: 6236 9535
Ms Gillian Tan
Senior Executive, Corporate Communications
Office: 6236 9529