Time to look beyond search for gene mutations: Experts

Lung cancer cells (green) cultured with normal lung cells (red). Research on lung cancer should no longer just be about finding specific gene mutations, or drugs that can block them, says Associate Professor Tan Eng Huat from NCCS.
Lung cancer cells (green) cultured with normal lung cells (red). Research on lung cancer should no longer just be about finding specific gene mutations, or drugs that can block them, says Associate Professor Tan Eng Huat from NCCS.PHOTO: WEIZMANN INSTITUTE OF SCIENCE

Lung cancer may be the poster child for precision medicine, following the development of drugs that can exploit weaknesses in specific gene mutations.

But it is now time to look beyond that area of research, say cancer researchers here.

It should no longer just be about finding specific targets, or drugs that can block them, said Associate Professor Tan Eng Huat from National Cancer Centre Singapore (NCCS).

"We need to analyse the complex genetic data of the cancer - including its gene expression and alteration - to come up with a better understanding of what really drives the cancer in individual patients," said the senior consultant from NCCS' medical oncology division.

"We have to move away from giving one form of treatment to a large group of patients and hoping that a significant proportion respond."

Lung cancer research made breakthroughs when scientists uncovered weak spots in two gene mutations - epidermal growth factor receptor and anaplastic lymphoma kinase - which they found were vulnerable to certain compounds.

These gene mutations occur in non-small cell lung cancer, which makes up more than 80 per cent of lung cancers here.

The discoveries led to the development of oral anti-cancer drugs, which have improved the median survival rate of cancer patients with these mutations. In Singapore, this applies to over 60 per cent of nearly 7,000 new lung cancer cases diagnosed between 2010 and 2014.

But as Prof Tan points out, the cancer in many patients becomes resistant to the drug in about one year.

Hence oncologists and scientists from NCCS and the Agency for Science, Technology and Research (A*Star) are working to find new ways to suppress the cancer, said Dr Daniel Tan, senior consultant at the NCCS medical oncology division.

The team received a research grant of close to $9 million from the National Medical Research Council in 2013 to do its studies. The sum is being disbursed to the team over five years.

"We are trying to exploit differences between normal cells and cancer cells, and between cancer cells and cancer stem cells," Dr Tan explained.

"Genetic mutations are one way, but we are moving into the realm where we are looking for any kind of characteristics we can exploit."

For example, scientists from A*Star have focused their attention on metabolic differences between cancer cells and cancer stem cells.

Cancer stem cells cause tumours to grow and are usually resistant to treatments such as chemotherapy and radiation. They are also linked to cancer relapses.

Metabolism refers to the chemical processes needed to maintain life.

"Understanding this will tell us which enzymes are controlling the metabolic cycle, and this will allow us to target the cancer cells specifically while sparing the rest of the cells in the body," said Dr Tam Wai Leong, a senior research scientist at A*Star's Genome Institute of Singapore.

Trials are also under way to find out if combination therapies, where two drugs are used to treat the patient instead of one, are effective.

Dr Tan noted that using a single drug is not always effective as the cancer finds an alternative pathway to continue wreaking havoc on the body. Hence researchers are now testing the use of a second drug to block that path.

"But whether or not they will truly result in double the effectiveness or cause an alternative mechanism to emerge is something we will find out in the coming months to a year," he said.


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A version of this article appeared in the print edition of The Straits Times on September 14, 2016, with the headline 'Time to look beyond search for gene mutations: Experts'. Print Edition | Subscribe