Singapore clinicians and scientists have discovered an unprecedented use of an FDA-approved drug to kill p53-defective cancer cells
Singapore clinicians and scientists have discovered an unprecedented use of an FDA-approved drug to kill p53-defective cancer cells
SINGAPORE, 15 February 2019 – Scientists from A*STAR’s Institute of Molecular and Cell Biology (IMCB) have discovered that niclosamide, an FDA-approved anti-parasitic drug, can effectively kill p53-defective cancer cells, potentially increasing the specificity for cancer targeting and sparing normal cells that carry wildtype p53 (the p53 gene in its natural or non-mutated form). These findings were published in leading scientific journal Nature Communications.
Mutations of the p53 gene in the human body is the one of the most common occurrences found in cancer cells and is present in over 50% of cancers. The p53 gene is a tumour suppressor gene that inhibits the growth of tumours, and if this gene is mutated, cancer cells are able to thrive.
Working in collaboration with researchers from A*STAR’s Bioprocessing Technology Institute and p53 Laboratory, the Skin Research Institute of Singapore, Duke-NUS Medical School, the Cancer Science Institute of Singapore, KK Women’s and Children’s Hospital,National Cancer Centre Singapore, and National University of Singapore, the IMCB research team found that niclosamide, a drug conventionally used in the treatment of intestinal tapeworm infections, induces metabolic stress in colon cancer cells without p53, thereby effectively causing death of these cancer cells. This discovery supports the potential use of niclosamide as a first-in-class drug against a broad spectrum of tumours deficient in p53 functions.
“The advantage of repurposing an FDA-approved drug for novel indications is the quicker time-to-market since information on their pharmacology and potential toxicity is already available. This can help to reduce cost and time in developing new candidate therapies and speed up the pipeline of available therapeutics redirected for targeting cancers,” said Dr Chit Fang Cheok, Principal Investigator at A*STAR’s IMCB and lead researcher of the study.
Dr Cheok added that by identifying how niclosamide works to target p53-defective cancer cells, this could also pave the way to new therapeutics against p53 mutations.
“A key challenge of cancer therapy today is the lack of response of some tumours to standard chemotherapy methods. There is an increasing realisation that personalised or targeted therapy may be an important step to improve the effectiveness of cancer treatment for patients,” Dr Cheok said.
Moving forward, the research team plans to test the efficacy of niclosamide against a broader cohort of tumour types.
For more information, please refer to the paper “Mitochondrial uncoupling reveals a novel therapeutic opportunity for p53-defective cancers”, published online by the journal Nature Communications on 26 September 2018.
Link to online version:
https://www.nature.com/
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About A*STAR’s Institute of Molecular and Cell Biology (IMCB)
The vision of Institute of Molecular and Cell Biology (IMCB) is to be a premier cell and molecular biology institute which addresses the mechanistic basis of human diseases and its mission is to conduct cutting-edge discovery research in disease pathways; to groom early career researchers to be future leaders in research; and to collaborate with medical and industry communities for research impact. IMCB plays an important role training and recruiting scientific talents, and has contributed to the development of other research entities in Singapore. Its success in fostering a biomedical research culture in Singapore has catalysed Singapore’s transformation into an international hub for biomedical research, development and innovation.
Funded by A*STAR, IMCB’s Discovery research comprises 5 major programmes: Cancer Cell Signalling, Multi-Modal Molecular (M3) Biology, Epigenetics and Diseases, iPS cell and Regenerative Medicine, and Technology and Translation. IMCB’s technologies and platforms focus on Genome-wide RNAi, Humanized Mouse Models, Proteomics and Protein Engineering, Gene Therapy and Gene Editing, and Molecular Histopathology.
For more information about IMCB, please visit www.imcb.a-star.edu.sg.
About the Agency for Science, Technology and Research (A*STAR)
The Agency for Science, Technology and Research (A*STAR) is Singapore’s lead public sector agency that spearheads economic oriented research to advance scientific discovery and develop innovative technology. Through open innovation, we collaborate with our partners in both the public and private sectors to benefit society.
As a Science and Technology Organisation, A*STAR bridges the gap between academia and industry. Our research creates economic growth and jobs for Singapore, and enhances lives by contributing to societal benefits such as improving outcomes in healthcare, urban living, and sustainability.
We play a key role in nurturing and developing a diversity of talent and leaders in our Agency and research entities, the wider research community and industry. A*STAR’s R&D activities span biomedical sciences and physical sciences and engineering, with research entities primarily located in Biopolis and Fusionopolis. For ongoing news, visit www.a-star.edu.sg.
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