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Singapore Researchers Discover New Biomarker for Cancer Prognosis

Duke-NUS scientists identify MBNL1 as a cancer biomarker associated with poorer disease outcomes, opening new doors for cancer therapeutics.

Cancer incidence worldwide continues to increase, with the World Health Organisation (WHO) estimating that the global cancer burden in 2018 had risen to 18.1 million new cases and 9.6 million cancer deaths. According to WHO, nearly half of new cancer cases and more than half of cancer deaths worldwide in 2018 were estimated to be in Asia, due to the proportion of the global population living in this region.

Methods of cancer diagnosis and treatment have consistently been a research focus of scientists and doctors worldwide, further spurred on by the rising disease burden of cancer. Research into cancer biomarkers has also brought to light several new methods of diagnosing and combatting cancer.

Biomarkers, or biological markers, are molecules, genes, or characteristics that can be used to identify pathological or physiological processes and diseases. Applied to the context of cancer, biomarkers are often molecules produced either by the body or by tumours, that help to characterise some cancers, and may play a role in cancer treatment.

There are three main categories of cancer biomarkers – predictive biomarkers help to foresee the efficacy of therapeutic intervention, prognostic biomarkers provide information on cancer progression and disease outcomes, and diagnostic biomarkers, as their name suggests, are used to identify specific types of cancers.

A recent study conducted by a team of scientists from Duke-NUS Medical School (Duke-NUS) identified a new biomarker for cancer prognosis, known as the Muscleblind-Like Splicing Regulator 1 (MBNL1) protein.

Published in Proceedings of the National Academy of Sciences (PNAS) in July 2020, the findings of this study could contribute towards the development of improved cancer treatments with higher efficacy and reduced side effects.

Dr Debleena Ray, Senior Research Fellow at the Duke-NUS Cancer and Stem Cell Biology (CSCB) programme, is the lead author of this study. “We discovered a mechanism involving MBNL1 protein that predicts several characteristics of cancer such as progression and relapse.”

“We found that MBNL1 protein is present in low amounts in many of the common cancers in the world, including breast, colorectal, stomach, lung and prostate cancers, which when combined account for about 49 percent of all cancers diagnosed in 2018. This can cause poor overall survival in many of these commonly-occurring cancers,” explained Dr Ray.

Besides their discovery of MBNL1 as a promising biomarker for prognosis in several cancers, the team also found that the mechanism linking MBNL1 with poorer outcomes in cancer also involves the c-Jun N-terminal kinase (JNK) pathway and specifically the JNK protein, which is often implicated in cancer and targeted in cancer treatments.

This suggests that inhibiting the JNK protein could be a potential therapeutic method in the treatment of cancers related to altered MBNL1 levels, and that MBNL1 levels could be used to monitor the efficacy of JNK inhibitors in cancer treatment.

“While JNK inhibitors have been tested as a cancer drug previously, currently there are no clinical trials for the same. However, if in the future there is a JNK inhibitor against cancer, MBNL1 could be used as a biomarker to select patients for the treatment,” said Adjunct Associate Professor David Epstein, also from Duke-NUS’ CSCB programme, and the study’s co-corresponding author.

Professor Patrick Casey, the Senior Vice Dean for Research at Duke-NUS, noted: “This study provides important information about novel targets and biomarkers that are implicated in several major cancers, which could lead to the development of new treatment strategies that can improve the lives of patients.”

The Duke-NUS team is currently building on their findings and investigating MBNL1 specifically in colorectal cancer, as well as employing antisense technology to inhibit gene expression, in order to develop a potential JNK-targeting cancer treatment. [APBN]