Researchers from the National Cancer Centre Singapore (NCCS) and the A*STAR’s Genome Institute of Singapore (GIS) supported by the National Medical Research Council (NMRC) Translational and Clinical Research (TCR) flagship program Precision Medicine in Liver Cancer across Asia-Pacific Network (PLANET) have made a discovery that could transform the treatment of Hepatocellular carcinoma (HCC), the most common but deadly type of liver cancer.
The discovery revealed that the genetic characteristics of liver cancer tumours can vary widely, not only across different patients but also within a single tumour.
This hinted that healing the patient needs a precision medicine, which is a treatment customised to the needs of each patient.
Until the discovery was found, it has been assumed that each case of liver cancer was caused by a single type of genetic mutation, but doctors have been wondering why Sorafenib, the standard drug used for liver cancer, has been ineffective in preventing recurrence in most patients after the tumour has been removed by surgery.
In fact, the tumour can contain several mutations - which differ widely across patients - and the key to successful treatment may lie in identifying and targeting those mutations responsible for recurrence.
Joint-lead author and GIS Human Genetics Group Leader Associate Prof Roger Foo said, “Our approach reveals that liver cancer may contain many more genetic mutations, targetable by drugs that are already available.”
“Re-positioning of drugs offers the hope of immediate treatment, on top of ongoing strategies for new drug discovery. We hope to build on our study to devise ever more means of precision therapy for liver cancer,” Prof Foo said.
The fact was not previously known because the cancer has traditionally been diagnosed with a single biopsy, a procedure which extracts a single tissue sample from the liver.
Prof Pierce Chow, the liver surgeon leading the NCCS team in this collaboration said, “Although early stage HCC can be well treated by surgical resection and transplantation, no subsequent adjuvant systemic therapy is currently available. Thus long-term outcomes even in early HCC are significantly poorer compared with other common cancers where good adjuvant systemic therapy is available after surgical resection.”
Prof Chow said this will help both early and late stage patients with HCC.
“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,” he said.
Comparing cancer that has recurred at another part of the liver after surgery, to that of the original tumour, they further found that the cancer cells giving rise to the recurrent cancer can arise from before or after genetic diversification of the original tumour.
These recurrent tumours diversified more quickly than expected in the distant sites, into many different clones, suggesting that each patient with HCC needs to be treated differently.
Co-lead author Dr Zhai Weiwei, Senior Research Scientist of Human Genetics at GIS commented, “This work sheds light on the genomic profile and evolutionary trajectories of HCC. The deeper understanding of HCC gained from our study provides a solid foundation for future therapeutic strategies.”
The researchers now looking at existing drugs used for other cancers that might work on liver cancer, since some of the mutations they found are also present in other cancers.
Their findings were recently published in the journal Nature Communications.
With funding from Singapore's National Medical Research Council, they are also collaborating with scientists in other Asia-Pacific countries, extending their study to more patients to collect further data to better understand and more effectively treat liver cancer across different ethnic groups.
Liver cancer is the second deadliest cancer in the world after lung cancer, the median five-year survival rate for liver cancer is 57 percent.