Cancer cells are biologically different from normal cells. Despite these differences, many current anti-cancer therapies are unselective, meaning they kill both cancer and normal cells equally. This lack of selectivity is the major source of treatment side effects in patients.

Dr Siang Koh’s laboratory aims to address this by developing cancer-specific treatment strategies. They study cellular abnormalities found in cancer and use this knowledge to identify drugs that target them, in the hopes of discovering better and kinder treatment options that improve quality of life. The group focuses on three themes:

1. Understanding cancer initiation. Abnormalities such as BRCA1/2 gene mutations in cells and environmental toxins (like alcohol) have been known to increase cancer risk. The team studies how these mutations and toxins work together to turn normal cells into cancer cells. Insights will enable early cancer detection, allowing better disease management and preventative measures in high-risk patients. 
2. Designing potent drug regimens. Small differences in chemotherapy doses will lead to severe toxicities. A potential solution is to use targeted drugs that attack cancer-specific abnormalities. They have identified how a class of drugs called ATR/CHK1 inhibitors amplify cellular stress in pancreatic cancer but not in normal tissues, leading to an ongoing drug combination trial for patients with advanced tumours. 
3. Beating drug resistance. Cancer relapse occurs when a previously effective drug no longer works, and the group is searching to identify ways to prevent this. They have found how abnormalities in a RAS-related protein cause resistance to one class of drugs but sensitivity to another class of drugs. Findings will help clinicians select the right drug for the right patient at the right time.

https://www.bristol.ac.uk/people/person/Siang%20Boon-Koh-8f78afe5-7c0d-4b86-93ccd4908d201c71/

Publications:

• Koh SB (2022). The expanding role of WEE1. Cellular Signalling. 
• Koh SB and Ellisen LW (2021). Immune activation and evolution through chemotherapy plus checkpoint blockade in triple-negative breast cancer. Cancer Cell.
• Koh SB et al. (2021). RASAL2 confers collateral MEK/EGFR dependency in chemoresistant triple-negative breast cancer. Clinical Cancer Research.