N2CR

27/09/2025

The Straits Times has featured one of our members, Prof Chng Wee Joo, a blood cancer specialist and the inspirational story of one of his patients.

27/09/2025

Congratulations to our primary members who have been recognised among the world’s top-cited scientists in the latest database developed by Stanford University and published by Elsevier. This recognition, based on Scopus citation metrics, places them in the top 2% of their respective fields — an outstanding achievement that reflects their exceptional research impact.

04/09/2025

Prospective Evaluation of QPOP in Relapsed/Refractory Non-Hodgkin’s Lymphoma

Treatment of relapsed/refractory non-Hodgkin’s lymphoma (R/R-NHL) remains one of the most difficult challenges in haematologic malignancies, with many patients exhausting standard therapies and facing limited treatment options. In a final report extending on interim results from a prospective study led by Dr Anand Jeyasekharan and A/Prof Edward Chow at NCIS and NUS, a novel AI-guided ex vivo drug screening tool, Quadratic Phenotypic Optimisation Platform (QPOP), accurately predicted response to drug combinations in 74.5% of 117 lymphoma cases.

Those who received QPOP-guided patient-specific treatment had a 59% overall response rate and nearly 60% experienced longer response duration compared to their preceding treatment. Two-year survival analysis revealed significant extension of progression free survival in QPOP-guided group compared to those on standard salvage regimens (P=0.019), with 44% lower risk of progression. These findings demonstrated clinical utility and potential of QPOP as a functional precision medicine platform, supporting its development as a clinical decision support tool in the management of R/R-NHL patients.

PURPOSEDespite initially responding to first-line treatment, many patients with non-Hodgkin's lymphoma (NHL) eventually relapse or are refractory. These patients are empirically subjected to salvage therapies that may not be efficacious. We had previously ...

01/09/2025

Overcoming Drug Resistance in Liver Cancer

Sorafenib is a first-line therapy used to treat advanced liver cancer, but its effectiveness is often reduced due to resistance in cancer cells. This study co-led by N2CR member, A/Prof Gautam Sethi, explored the biological mechanisms behind that resistance and identified a group of genes involved in retinoic acid metabolism that help cancer cells survive treatment.

These genes are activated by a protein called POU3F3, which boosts the production of retinoic acid—a compound that protects cells from damage. By silencing POU3F3, researchers were able to make cancer cells more responsive to sorafenib. They also identified a compound called rosarin that inhibits POU3F3 and enhances the drug’s effectiveness. Laboratory and animal tests showed that combining rosarin with sorafenib significantly improved treatment outcomes. These findings suggest that targeting POU3F3 could be a promising strategy to overcome drug resistance and improve the success of liver cancer therapies.

https://rdcu.be/eCYaH

13/08/2025

Overcoming Drug Resistance in Leukemia

Venetoclax (VEN) is a targeted therapy used to treat chronic lymphocytic leukemia and acute myeloid leukemia. It works by blocking Bcl-2, a protein that prevents cells from undergoing programmed cell death, known as apoptosis, thus allowing cancer cells to survive. However, some cancer cells become resistant by switching to rely on another survival protein called Mcl-1.

This study led by N2CR members, Prof Shazib Pervaiz and Dr Stephen Chong, found that in VEN-resistant cells, increased levels of superoxide—a reactive oxygen molecule inside cells—activate a signaling protein called AKT which phosphorylates and stabilizes Mcl-1 to help cancer cells resist VEN and survive. Reducing superoxide or blocking AKT reverses this resistance. Combining VEN with an AKT inhibitor (capivasertib) significantly reduced resistant cancer cells and improved survival in mice, offering a promising new treatment strategy.

https://bit.ly/3JtTFMy

07/08/2025

Congratulations to Dr Alan Prem Kumar on receiving the Graduate Mentor of the Year (GRAMAY) Award 2025.

This is an annual award that honours and celebrates faculty staff for their excellence in mentorship and the professional development of graduate students in the Yong Loo Lin School of Medicine. The award is given to recognise the important key roles played by the Faculty staff in inspiring and nurturing future biomedical- and clinician-scientists. The award recipients should have shown excellence in graduate supervision, intellectual and professional development as well as career development of their graduate students.

01/08/2025

N2CR had its 3rd retreat at Grand Copthorne Waterfront Hotel on 25 July 2025.

From inspiring discussions and exchanges to a relaxing evening by the river with good food, drinks as well as meaningful conversations — it was a day to remember.

A big thank you to everyone who joined us!

01/07/2025

Last week, CSI Singapore together with N2CR & A*STAR IMCB, hosted a symposium with speaker - Prof. Patrick Chinnery, from the UK Medical Research Council (UK Research and Innovation). He spoke on the topic “An Evolving Symbiosis: Mitochondria in Health and Disease”.

N2CR Agency for Science, Technology and Research (A*STAR)

20/06/2025

Enhancing Lenalidomide Efficacy in Multiple Myeloma

Multiple myeloma (MM) is a type of blood cancer that originates from abnormal plasma cells in the bone marrow, leading to serious complications such as bone damage, anaemia, kidney dysfunction, and an increased risk of infections.

A cornerstone of MM treatment involves immunomodulatory drugs (IMiDs), such as lenalidomide, which work by binding to the protein Cereblon (CRBN). This interaction triggers the breakdown of several proteins critical for the survival and growth of MM cells. However, many patients eventually develop resistance to lenalidomide, leading to disease relapse.

Recent research, co-led by Prof Chng Wee Joo, A/Prof Polly Chen, and Dr Teoh Phaik Ju, has identified a new mechanism of resistance beyond the previously understood CRBN pathway, involving the RNA-editing enzyme, named ADAR1. The study reveals that ADAR1 interferes with lenalidomide’s activity by altering the structure of double-stranded RNA (dsRNA). This mechanism would lead to the suppression of the immune response triggered by lenalidomide, thus, reducing its effectiveness in killing myeloma cells.

These findings highlight ADAR1 as a promising therapeutic target to overcome lenalidomide resistance in MM. With ADAR1 inhibitors currently in preclinical development, combining them with lenalidomide could offer a more effective therapeutic approach and improve patient outcomes.

https://bit.ly/3SZ4Zlu

Key PointsLenalidomide induces immunomodulating responses through the activation of dsRNA-sensing pathway.ADAR1 drives lenalidomide resistance in MM via th

17/04/2025

Congratulations Dr Anand Jeyasekharan on being accepted as a NextGen Star at the American Association for Cancer Research (AACR) Annual Meeting 2025!

This recognition is a testament to your outstanding contributions to cancer research.

09/04/2025

Genetic Testing in Asian Cancer Patients: Early Detection and Prevention

Multiple primary cancers (MPC) often indicate a hereditary cancer predisposition syndrome. In a study led by Prof Lee Soo Chin, 19% of 3514 cancer patients who underwent germline genetic testing through a cancer genetics clinic had MPC and 29.4% of these MPC patients tested positive for at least one pathogenic germline variants (PGVs), compared to 20.8% positivity rate among patients with single primary cancer. PGVs are inherited genetic mutations that increase the risk of developing certain diseases, including cancer.

The findings underscore the importance of comprehensive genetic testing for MPC patients to better identify and manage hereditary cancer risks. This approach will refine genetic testing, enhance early detection, personalise cancer treatment and prevention strategies, thereby advancing the field of precision medicine.

https://bit.ly/426s8b2

13/03/2025

Predicting CLL Treatment with BCL-2 Dependence

Chronic lymphocytic leukemia (CLL) is a type of cancer that affects the blood and bone marrow, leading to the buildup of abnormal lymphocytes. It is the most common form of leukemia in adults. While genetic markers help with chemoimmunotherapy, new markers are needed for targeted therapies.

A multinational team of researchers, with first-author Dr Stephen Chong Jun Fei from N2CR, used BH3-profiling and various genetic and molecular data to find new treatment response markers. In 73 CLL patients, higher dependence on the BCL-2 protein was linked to better genetic markers and drug sensitivity. This was confirmed in cell studies and additional patients, showing BCL-2 dependence predicted positive treatment responses. BCL-2 dependence could be a useful marker for predicting CLL treatment response, helping to tailor therapies more effectively.

https://bit.ly/4hz7ip8

Background Established genetic biomarkers in chronic lymphocytic leukemia (CLL) have been useful in predicting response to chemoimmunotherapy but are less predictive of response to targeted therapies. With several such targeted therapies now approved for CLL, identifying novel, non-genetic predictiv...