SINGAPORE TAKES ON CANCER WITH INNOVATIVE STREAK
Although 2020 was more focused on finding solutions to fight the COVID-19 pandemic, it also pushed the boundaries of cancer prevention, diagnosis and treatment. Researchers across Asia have continued to make meaningful strides against cancer in 2020. One such remarkable example is that of Singapore. The scientific community across the country is setting new examples of innovation by focusing majorly on two aspectschemotherapy and immunotherapy, to fight this deadly disease. While the socioeconomic burden inflicted by cancer is inevitable, Singapore’s innovative streak for developing effective treatment of cancer is set to mitigate this socioeconomic impact, and help patients maintain their quality of life, and remain productive.
Although 2020 was more focused on finding solutions to fight the COVID-19 pandemic, it also pushed the boundaries of cancer prevention, diagnosis and treatment. Researchers across Asia have continued to make meaningful strides against cancer in 2020. One such remarkable example is that of Singapore. The scientific community across the country is setting new examples of innovation by focusing majorly on two aspects- chemotherapy and immunotherapy, to fight this deadly disease. While the socioeconomic burden inflicted by cancer is inevitable, Singapore’s innovative streak for developing effective treatment of cancer is set to mitigate this socioeconomic impact, and help patients maintain their quality of life, and remain productive.
Worldwide, an estimated 19.3 million new cancer cases and almost 10 million cancer deaths occurred in 2020, as per the GLOBOCAN 2020 report. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated
2.3 million new cases (11.7 per cent), followed by lung (11.4 per cent), colorectal (10 per cent), prostate (7.3 per cent), and stomach (5.6 per cent) cancers. The global cancer burden is expected to be 28.4 million cases in 2040, a 47 per cent rise from 2020.
For both sexes combined, one-half of all cases and 58.3 per cent of cancer deaths are estimated to occur in Asia in 2020, where 59.5 per cent of the global population resides. In contrast to other
regions, the share of cancer deaths in Asia (58.3 per cent) and Africa (7.2 per cent) are higher than the share of incidence (49.3 per cent and 5.7 per cent, respectively) because of the different distribution of cancer types and higher case fatality rates in these regions.
Although 2020 was more focused on finding solutions to fight the COVID-19 pandemic, it pushed the boundaries of cancer prevention, diagnosis and treatment. Researchers across Asia have continued to make meaningful strides against cancer in 2020. One such remarkable example is that of Singapore.
Due to the innovations arising within the region as well as the world-renowned healthcare system that the country boasts, Singapore attracts a myriad of medical professionals, academic researchers and healthcare-focused companies.
According to the Ministry of Health at Singapore, cancer is the number one killer in the country, with an average of 41 people getting diagnosed with cancer every day, and 15 people die from cancer every day. In particular, lung, colorectal and breast cancer are amongst the leading causes of cancer-related deaths in Singapore.
As a result of which, the scientific community across the country is setting new examples by focusing majorly on two aspects- chemotherapy and immunotherapy, to fight this deadly disease.
Efficacy of chemotherapy
Although chemotherapy is a powerful and one of the most common forms of cancer treatment that uses drugs to destroy cancer cells, there are conditions when it is no longer effective against cancer or in minimizing symptoms.
But now cancer patients who are undergoing chemotherapy can look forward to a new blood test that could tell their doctors whether the treatment is working, within one day after the start of the treatment. This will significantly speed up the evaluation process and enable doctors to make adjustments to the treatment plan, if necessary, to improve patients’ chances of recovery.
This has been made possible by the Department of Biomedical Engineering and Institute for Health Innovation & Technology (iHealthtech) at the National University of Singapore (NUS) where researchers have developed a technology that is accurate, less invasive and significantly brings forward the evaluation window, by using liquid biopsies. A patent has been filed for the technology and the NUS team hopes to bring this technology to market in the next three years.
“The technique, termed extracellular vesicle monitoring of small-molecule chemical occupancy and protein expression (ExoSCOPE), is the first of its kind in the world. It takes advantage of extracellular vesicles (EVs) secreted by cancer cells and circulating in blood as a reflective indicator of drug effectiveness in solid tumours. Conventional procedures such as tumour imaging are not only expensive but also delayed. For these methods, treatment effectiveness can only be determined
after weeks. Using the ExoSCOPE, we can directly measure the outcomes of drug effectiveness within 24 hours of treatment initiation. This will significantly reduce the time and cost for cancer treatment monitoring”, explains Dr Shao Huilin, Assistant Professor, Department of Biomedical Engineering, National University of Singapore.
On the other hand, a team of researchers at the NUS Yong Loo Lin School of Medicine is studying the resistance of cancer cells to chemotherapy that is marked by changes and increased output of certain proteins.
“We have identified how a molecule called DUSP16 plays an important role in a cancer patient’s response to chemotherapeutic drugs. Analysis of head and neck cancer patients, and breast cancer patients showed that those with higher DUSP16 expression in their cancer cells lived for significantly shorter periods compared to patients with lower levels of DUSP16. DUSP16 expression can thus be used as a biomarker for sensitivity of cancer patients to chemotherapy, which will be important for clinicians seeking to design suitable treatment”, says Professor Goh Boon Cher, Deputy Director, Cancer Science Institute of Singapore, NUS.
Researchers from the Cancer Science Institute of Singapore have also discovered a way to predict which patients are resistant to platinum chemotherapy, given in case of ovarian cancer. From their investigation, an association was found between patients whose cancers had high levels of the DNA repair protein, RAD51, and the time to relapse after platinum chemotherapy.
“RAD51 has been identified as a biomarker which can potentially be used to determine the resistance of ovarian cancer to platinum chemotherapy. We used a state-of-the-art automated microscopy method to image and accurately quantify the amount of RAD51 protein present in each tumour cell. Our findings offer a route to refine platinum use in ovarian cancer”, says Dr Anand Jeyasekharan, Principal Investigator & Facility Head (Microscopy), Cancer Science Institute of Singapore, NUS.
Further, researchers from Duke-NUS Medical School and the Agency for Science, Technology and Research (A*STAR) have reported that ETC-159, a made-in-Singapore anti-cancer drug that is currently in early phase clinical trials for use in a subset of colorectal and gynaecological cancers, could prevent some tumours from resisting therapies by blocking a key DNA repair mechanism.
Providing another solution in this space,
Vela Diagnostics has recently announced a collaboration with the National Cancer Centre of Singapore (NCCS) to develop a molecular diagnostic assay to predict individual patients’ responses to a cancer therapy called Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitors (TKIs).
“Being able to predict an individual’s response will help clinicians determine if EGFR-TKIs are a suitable therapeutic option for the patient. The assay is now being developed by Vela Diagnostics and the validation of the assay will be done at NCCS. The next phase of the collaboration will evaluate the efficacy of the assay through a clinical trial to test the response of patients to EGFRTKIs. These will include patients with head and neck cancers based on the original discovery, and also other similar types of cancers arising from the lung, oesophagus, bladder and cervix”, points out Dr Charlie Lee, R&D Head, Vela Diagnostics, Singapore.
Dark side of chemo
Despite the urgent need to find more accessible and better treatment options for cancer, the standard of care in many situations remains a combination of chemotherapy, surgery, and radiotherapy. All of which have been standard treatments of cancer for decades now. However, despite ongoing efforts to improve the therapies and reduce adverse effects, there remain substantial side effects. For example, one commonly known and identified side effect is the loss of hair.
While determining the effectiveness of chemotherapy for cancer treatment is a critical factor, there is also a requirement to address the side-effects generated by the chemotherapy procedure. Every person doesn’t get every side effect, and some people get few, if any because the severity of side effects varies greatly from person to person.
To address this concern, a team of clinicians at the NUS has partnered UK-based Paxman Coolers to develop a device that may prevent or reduce numbness and pain caused by chemotherapy.
“Chemotherapy-induced peripheral neuropathy (CIPN) is a severe side-effect of chemotherapy drugs called taxanes, which are used to treat common cancers such as breast, lung, ovarian and stomach cancer. Pilot studies for the device will commence in Q2 2022 to investigate the device in healthy volunteers, and cancer patients undergoing CIPN-causing chemotherapy”, says Dr Aishwarya Bandla, Head of Translational Tx Core, N.1 Institute for Health, NUS.
On the other hand, a technique which has fewer side effects compared with conventional chemotherapy has been successfully introduced at the National University Hospital (NUH) and
“Being able to predict an individual’s response will help clinicians determine if EGFRTKIs are a suitable therapeutic option for the cancer patient. The assay is now being developed by Vela Diagnostics and the validation of the assay will be done at NCCS.”
“Chemotherapy-induced peripheral neuropathy (CIPN) is a severe side-effect of chemotherapy drugs called taxanes, which are used to treat common cancers such as breast, lung, ovarian and stomach cancer.”
“This partnership will combine Hummingbird’s Rational Antibody Discovery (RAD) platform and EDDC’s proprietary High Throughput Antibody Discovery (HiTAD) platform, to realise the goal of bringing made-in-Singapore innovation to the world.”
“We have identified how a molecule called DUSP16 plays an important role in a cancer patient’s response to chemotherapeutic drugs. DUSP16 expression can thus be used as a biomarker for sensitivity of cancer patients to chemotherapy, which will be important for clinicians seeking to design suitable treatment.”
National University Cancer Institute, Singapore (NCIS). The Pressurised Intraperitoneal Aerosol Chemotherapy (Pipac) method distributes drugs in aerosol form through a device called a port directly into the abdomen via a catheter.
Moving a step forward in this direction, a research collaboration between Singapore and China has resulted in the development of DNAbased nanogels that break down and release their chemotherapeutic contents within cancer cells, minimizing the impacts on normal ones and potentially eliminating painful and uncomfortable side effects. This study is being funded by Northwestern Polytechnical University in China and A*STAR in Singapore.
“The technique, termed extracellular vesicle monitoring of small-molecule chemical occupancy and protein expression (ExoSCOPE), is the first of its kind in the world. It will significantly reduce the time and cost for cancer treatment monitoring.”
“The AVATASCAN screens the patient’s tumour samples across a panel of anti-cancer drugs to determine their efficacies in the patient-derived cells. These drug-response results, coupled with genetic data, are then presented to the oncologists to suggest drug treatment options”
“Over the past five years, Foundation Medicine (FMI), a molecular information company that is part of the Roche Group, has been providing comprehensive genomic profiling in Singapore to support physicians and patients in cancer care decisions.”
“RAD51 has been identified as a biomarker which can potentially be used to determine the resistance of ovarian cancer to platinum chemotherapy.”
Taking a precise route
In recent years, the research into cancer and its treatments has made significant strides towards not only helping patients increase their survival chances but also in developing more targeted therapies. One such route is called immunotherapy, a type of cancer treatment
that helps your immune system fight cancer.
And precision medicine is at the heart of immunotherapy that is currently one of the hottest areas of cancer research.
Immunotherapy can harness and enhance the body’s own immune defenses to fight cancer. Unlike traditional chemotherapies, which are chemical-based drugs that act directly on cancer cells to stop them from replicating, immunotherapies are biologically derived, and they boost the immune system’s ability to identify and destroy cancer cells. Antibody drugs are designed to bind to specific molecules which are present on cancer cells or immune cells, helping the immune system to recognise and destroy these cells.
To take things ahead in this direction, the Experimental Drug Development Centre (EDDC), Singapore’s national platform for drug discovery and development hosted at A*STAR, and Hummingbird Bioscience, a clinical-stage biotech startup, have entered a three-year partnership to develop novel antibodies for cancer
immunotherapy.
“This partnership will combine Hummingbird’s Rational Antibody Discovery (RAD) platform and EDDC’s proprietary High Throughput Antibody Discovery (HiTAD) platform, to realise the goal of bringing made-in-Singapore innovation to the world”, says Professor Damian O’Connell, Chief Executive Officer, EDDC.
Setting a new era in cancer immunotherapy these days is the concept of Chimeric Antigen Receptor (CAR) T-cell therapy which involves genetic modification of patient’s autologous T-cells to express a CAR specific for a tumor antigen, following by ex vivo cell expansion and re-infusion back to the patient.
Singapore has recently approved Kymriah as the first commercial chimeric antigen receptor T-cell (CAR-T) therapy under the new cell, tissue and gene therapy products (CTGTP) regulatory framework. Kymriah, a CD19-directed genetically modified autologous T-cell immunocellular therapy, is approved to treat two life-threatening cancers that have limited treatment options and historically poor outcomes, addressing the critical need for new therapies for these patients.
Kymriah has been developed by Swiss firm Novartis, in collaboration with the Perelman
School of Medicine at the University of Pennsylvania, a strategic alliance between industry and academia, which was first-of-its-kind in
CAR-T research and development.
This approval of the first CAR-T therapy has marked the next leap forward in precision medicine. Although Kymriah is a complex personalized therapy which needs collaboration between several stakeholders, the medical infrastructure in Singapore ensures effective drug delivery within treatment centers. It is heartening to know that great strides towards precision medicine are being made in the area of cancer immunotherapy within Singapore.
AVATAMED, a precision medicine service company based in Singapore, has announced the setting up of a joint lab with Singapore’s Institute of Molecular and Cell Biology (IMCB) at A*STAR, to offer precision oncology services. Together with IMCB’s technological platforms such as the highthroughput drug screening platform, and expertise in cancer and cell biology, the joint service lab will offer AVATAMED’s proprietary drug screening technology, the AVATASCAN and its software to oncologists and pharmaceutical companies.
“AVATAMED is a spin-off from A*STAR, so we are delighted to be back at where it all started. Precision medicine is the future, and we want to bring AVATASCAN to benefit patients and the industry. The AVATASCAN technology was born out of a decade of research at Samsung Medical Centre in South Korea, with accumulated drug response and genetic data of patient-derived tumours. The AVATASCAN screens the patient’s tumour samples across a panel of anti-cancer drugs to determine their efficacies in the patientderived cells. These drug-response results, coupled with genetic data, are then presented to the oncologists to suggest drug treatment options”, shares Toh Hong Boon, Chief Executive Officer, AVATAMED.
Adding on, Singapore Translational Cancer Consortium (STCC), National Cancer Centre Singapore (NCCS), the National University Cancer Institute, Singapore (NCIS) at the National University Hospital (NUH) and Roche have recently announced a unique and groundbreaking partnership between public and private sector institutions in Singapore aimed at establishing a critical infrastructure to advance the adoption of personalised healthcare in Singapore, including precision oncology.
“Over the past five years, Foundation Medicine (FMI), a molecular information company that is part of the Roche Group, has been providing comprehensive genomic profiling in Singapore to support physicians and patients in cancer care decisions. To support the application of precision oncology, Roche will provide access to comprehensive genomic profiling by FMI. Insights gained from the collection of high-quality, standardised genomic data in these databases can supplement or amplify clinical studies to help accelerate research and development, which we hope will ultimately optimise healthcare resources and increase chances of survival for even more people with cancer,” says Ryan Harper, General Manager, Roche Singapore.
On the whole, precision medicine is part of Singapore’s Research, Innovation, and Enterprise (RIE) 2025 strategic goal to transform healthcare in Singapore. Singapore’s Ministry of Health has identified precision medicine as an essential solution to understand how genomic, phenotypic, lifestyle and clinical factors contribute to health.
To achieve this, the Ministry has set up Precision Health Research, Singapore (PRECISE), as the central entity to drive National Precision Medicine (NPM) strategy and to address Singapore’s healthcare challenges in a sustainable and clinically cost-effective manner.
While the socioeconomic burden inflicted by cancer is inevitable, Singapore’s innovative streak for developing effective treatment of cancer is set to mitigate this socioeconomic impact, and help patients maintain their quality of life, and remain productive.