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Homing in on cancer cells, wherever they are

Tumour genomic sequencing and targeted therapy will play bigger role in treatments

Location, location, location is the mantra of real estate agents. Indeed, even identical homes can have very different values, depending on their location.

A home in the central district comes with a bevy of advantages such as connectivity, amenities and good schools. But over time, these traditional perks of living in a central locality are being eroded.

I was at a suburban mall in Sengkang on a recent weekend and could quite easily find most of what I needed in terms of food and merchandise. On top of that, the mall is easily accessible via the MRT. There is no real need to go to a downtown mall any more.

Medical oncologists used to be extremely obsessed with location too. Even for advanced cancer that has spread widely throughout the body, oncologists often opt for very different treatment strategies, though they are all based on the location where the cancer first began.

The original location of the cancer - whether in the breast, lung, colon or elsewhere - often determines the nature and behaviour of the cancer cells.

This primary location also, broadly, determines the types of chemotherapy drugs that should be used. However, over time, these medical paradigms are being eroded as well.

With the advent of comprehensive tumour genomic sequencing and targeted therapy, the type of genetic mutations driving the growth and immortality of the cancer will increasingly guide treatment decisions.

In time to come, oncologists may no longer have the obsessive need to pin down the primary location of the cancer.

KILLING CANCER, NOT NORMAL, CELLS

Targeted therapy is the cornerstone of this new precision medicine.

Conventional chemotherapy basically uses drugs that poison fast multiplying cells. These drugs are known as cytotoxics.

They work on the principle that cancer cells, on average, multiply much faster than normal cells and consequently suffer greater harm from cytotoxics.

Since normal cells multiply too, albeit more slowly, they suffer a degree of collateral damage. This explains many of the side effects associated with cytotoxics.

Using cytotoxics to destroy cancer cells is a bit like using an artillery barrage to kill enemy troops. The artillery may take aim at areas of troop concentration and avoid population centres but the accuracy is limited and civilian collateral damage invariably arises.

Targeted therapy, however, works on the principle of blocking specific genetic mutations in the cancer cells that confer on them a survival and growth advantage over normal cells.

This would be akin to the use of precision munitions in a war scenario to destroy the enemy's war-making power while minimising civilian casualty.

Precision warfare is very dependent on good military intelligence to locate the command and control centres of enemy forces so as to disable them.

Precision medicine with targeted therapy is analogously dependent on identifying the genetic mutations and associated growth signalling pathways so as to disrupt them.

The numerous genetic mutations that may potentially be present in cancer, however, make this task much like searching for a few needles in a haystack.

The technique of next-generation genetic sequencing has now armed oncologists with the ability to perform comprehensive genetic profiling of a cancer fairly quickly.

Once a targetable mutation is identified, the optimal therapy can then be selected, regardless of the primary location of the cancer.

The use of next-generation genetic sequencing has led to new insights. Mutations that were thought to exist almost exclusively in one particular tumour type are picked up with increasing frequency in other tumour types.

For instance, a mutation known as HER2, commonly found in breast cancers, can also be detected occasionally in colon cancers.

What is commonly found in breast cancers can also be found in colon cancer. This is just like what's happening in the retail scene - what is found in a downtown mall can also be found in a suburban mall.

And such types of colon cancers potentially respond well to a breast cancer drug trastuzumab.

Going beyond the confines of strategy determined by the primary location of the cancer in the body and pursuing, instead, treatment that will deliver the greatest blow to the cancer based on genetic information has allowed me to crack many a case of tough-to-treat cancers.

Sometimes we have to forget about "location, location, location".

•Dr Wong Seng Weng is the medical director and consultant medical oncologist at The Cancer Centre (Singapore Medical Group).

A version of this article appeared in the print edition of The Straits Times on December 19, 2017, with the headline 'Homing in on cancer cells, wherever they are'. Print Edition | Subscribe