Two different studies conducted by researchers from the Agency for Science, Technology and Research (A*STAR) in Singapore have provided new insights into personalised medicine in the diagnosis and treatment of cancer. Both studies focused on customised treatment of patients, which has potential to ease the public health burden particularly in countries where resources are limited.

“It is specifically because of this great health burden that drugs must be specific for each patient’s genetic and immunological profile. Non-personalized treatment wastes resources without benefitting the patient,” said Professor Pierce Chow, a senior consultant surgeon at National Cancer Centre Singapore (NCCS) and Singapore General Hospital (SGH).

Genetic diversity in liver cancer cells unravelled

Liver cancer is the second most common cause of cancer deaths in the world, and patients with hepatocellular carcinoma (HCC) have among the poorest survival rates. Due to a shortage of effective drugs for liver cancer, researchers from A*STAR’s Genome Institute of Singapore and NCCS studied the intra-tumour heterogeneity in HCC, and recently published their findings on the genetic diversity of individual liver cancers.

Using advanced DNA sequencing technology, researchers examined 66 liver tumour samples taken from nine patients and discovered a broad range of intra-tumoral genetic diversity in the samples, which demonstrated that the original cancer cells evolve to give rise to a diverse genomic make up. This provides insight as to why anti-cancer therapy for HCC is challenging.

“This work sheds light on the genomic profile and evolutionary trajectories of HCC,” said co-lead author and senior research scientist of Human Genetics, Dr Zhai Weiwei. “The deeper understanding of HCC gained from our study provides a solid foundation for future therapeutic strategies.”

In order to cover diverse ethnic and etiological backgrounds across the Asia-Pacific, the team of researchers has enrolled 100 patients in Malaysia, Philippines, Singapore and Thailand in their further studies.

“The data from this study and our prospective multi-centre study will potentially enable treatment to be individualised to the genomic and immunological make-up of each patient. This will help both early and late stage patients with HCC,” added Professor Pierce Chow, who co-authored the study.

Screening for adverse effects of anti-cancer drugs with stem cells

Another obstacle in the treatment of cancer is the side effects of anti-cancer drugs, which vary in different individuals and is difficult to predict.

In a separate four-year research project however, researchers at A*STAR’s Institute of Bioengineering and Nanotechnology (IBN) and NCCS discovered that stem cells are able to predict possible side-effects of drugs that are used in the treatment of cancer.

“Adverse side effects from drugs are a major clinical concern, which could and should be preventable,” said IBN’s Executive Director, Professor Jackie Ying. “Knowing whether an individual is susceptible to a particular medicine will improve healthcare and treatment outcome.”

By using induced pluripotent stem cells, scientists created liver cells from the blood of five patients with kidney cancer. These liver cells were then exposed to an anti-cancer drug, pazonpanib, from which three of the patients were known to suffer bad reactions.

The scientists discovered that the created liver cells exhibited the same drug sensitivity, and were also able to analyse how the drug resulted in liver damage.

“Our hypothesis was that liver cells made from the individual’s blood might show similar sensitivity or resistance to pazopanib,” said lead researcher Dr Min-Han Tan.

“This study is the first proof-of-concept that our approach can predict drug-induced liver damage for an individual. Importantly, we were able to figure out how the drug works from the way they react to the liver cells, which was unknown to doctors, even after many years of using this drug.”

“Currently, new drugs are tested for toxicity using generic liver cells, which cannot model patient-specific reaction. By personalising liver cells from the blood of individual patients, we can help doctors to prescribe safer and more effective therapies,” added co-researcher Professor Hanry Yu.

The team of researchers is planning formal clinical trials to study the mechanism of anti-cancer drugs and how they affect organs. MIMS

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