Applying Genetic Theory in Colorectal Cancer Treatment

Chinese & English Text | Debby Seng
Photo | Editorial Board with some provided by the interviewee

Faculty of Health Sciences Associate Professor Shim Joong Sup has identified Aurora Kinase A as the synthetic lethal partner of ARID1A in colorectal cancer cells. His team was among the first to apply the genetic theory of ‘synthetic lethality’ in the treatment of colorectal cancer. The study suggests that Aurora Kinase A is a precision cancer target for the ARID1A mutant colorectal cancer. This research, which has unveiled a new chapter in cancer treatment, has been published in Nature Communications.

ARID1A is a tumour suppressor gene. According to Prof Shim, one of the causes of colorectal cancer is genetic mutations, including oncogene mutations and tumour suppressor mutations. Current targeted cancer therapies focus primarily on inhibiting tumour oncogene. However, it has been a major clinical challenge to deal with tumour suppressor mutations, as they cannot be targeted by drugs.

Applying the genetic theory of ‘synthetic lethality’ in the treatment of colorectal cancer

Synthetic lethality is a genetic interaction between two (or more) genes where a single gene deficiency is tolerable for cell viability, whereas deficiencies in both genes lead to cell death. As cancer cells have existing deficiencies in at least one gene (tumour suppressor), the synthetic lethality approach for the mutant tumour suppressor enables medical personnel to target cancer cells precisely. Prof Shim says: ‘By using high throughput screening approach, we identified Aurora Kinase A as the synthetic lethal partner of ARID1A. When the ARID1A gene mutates, as long as the activity of the Aurora Kinase A is inhibited, the cancer cells can be killed precisely.’

Prof Shim’s team has achieved good research results in animal testing. The team’s next step is to expand the application of the synthetic lethality concept to other tumour suppressor genes in colorectal and other types of cancer. Prof Shim’s team is also committed to developing new Aurora Kinase A inhibitors to treat colorectal cancer cells carrying ARID1A mutations.

Prof Shim Joong Sup is currently studying a variety of tumour suppressor genes, including p53, PTEN, RB1, BRCA1, ARID1A, and SMAD4. He is committed to identifying their synthetic lethal partners. Before joining UM, he was a research associate at John Hopkins University School of Medicine in the United States. He is currently a member of the editorial board of the journal Molecular Medicine Reports.
ISSUE 22 | 2020

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