Thursday, 21 August, 2014

 
Published April 26, 2014
Wellness
Life-saving cancer 'avatars'
Drug testing on mice now available for the first time in Singapore. By Cheah Ui-Hoon
BT 20140426 UHCANCER26 1060354

PERSONALISED THERAPY
Champions Tumorgraft's principle is to test drugs against the patient's own tumour - grafted onto a colony of mice, so that they represent the tumour in the patient. - PHOTO: CHAMPIONS ONCOLOGY

BT 20140426 UHCANCER26 1060354

ONE of the most personalised and individualised approaches to cancer treatment is now available in Singapore - with the introduction of Champions Tumorgraft. While strides have been made through testing the molecular genetics in the patient's cancer and selecting the appropriate targeted agents, a faster and easier way for true personalisation is now available, says David Sidransky, an oncologist and chairman of Champions Oncology, which offers Champions Tumorgraft.

"Personalised therapy is important now in all medicine and especially in oncology," he says. "However, oncology medication deals with general situations and is not specific to the patient. The medication is effective in some 20-50 per cent of cases. About half of the patients won't receive benefits, and they lose time as well as accumulate toxicity through chemotherapy."

Champions Tumorgraft works on a different principle and it's primarily a diagnostic tool. Instead of "testing" drugs on the patient, the principle is to test drugs against the patient's own tumour - grafted onto a colony of mice, so that they represent the tumour in the patient. The understanding is that if the drug has the same effect on the tumour in the mouse, it will have an effect on the patients.

"This, we found, is the easiest and fastest way - to test drugs on an 'avatar' - and with 90 per cent accuracy," explains Dr Sidransky who was profiled by Time magazine in 2001 as one of the top physicians/scientists in America, in recognition of his work with early detection of cancer.

Mice are used because they're the biggest of small animals, are easy to breed and this particular breed has very little immune system so they are good "vessels" for the tumours implanted into them.

"The patient's tumour is put into some 20 to 30 mice, like growing a tumour bank. Once the tumours have successfully grown in the colony of mice, then testing begins, and this is a process which takes four weeks. It is important to note that a whole colony is needed to support the process," says Dr Sidransky.

Creating this living colony is a personalised and continuous system. A colony takes three months to grow, and testing takes another four weeks. "But once you go through the trouble of growing the colony, the accuracy is 90 per cent for selecting drugs through this process," he points out.

Statistics show that about 50 per cent of cancer patients will have their cancer recur, and go into second line therapy. Only about 15 per cent will benefit from the second round of therapy in current conventional treatments. With this new method that provides a high chance of finding the best drug for the patient, the chances of the personalised drug working get raised to 90 per cent as well.

"The typical benefit is that the tumour will shrink in six to nine months. Finding the best therapy is the main aim, and toxicity is also minimised."

Dr Sidransky says that all 12 solid cancer tumours have been successfully tried in this method, as they form 95 per cent of cancers that people get.

For now, Champions Tumorgraft is recommended for selection of second-line therapy as the main disadvantage is the time lag required for the whole process, beginning from the growing of the colony (which takes up to three months) to the testing of drugs on this colony of mice (one month minimum). Molecular testing is the first stage, to gain knowledge of what type of drugs might best benefit a patient. But the empirical testing of various drugs on mice is much more accurate and the information can be used to guide the testing.

"We either find something that works immediately, or the information guides further testing," says Dr Sidransky. He says that tumour-grafting for testing was a technology that was first published in 2002, but last year, there were 3,000 publications on the technology. "It's completely penetrated the academic setting with every major pharmaceutical company doing it. But we're the only ones doing it for patients, while still being able to establish models and develop drugs."

"Time is a very important factor," notes Ang Peng Tiam, medical director of Parkway Cancer Centre, which is a partner of Champions Tumorgraft, "when it comes to selecting the right patients for this diagnostic tool because the entire process, from the implantation of the tumour in the mice to obtaining the results of the drug testing, takes about three to four months."

With sufficient time, this technology can be suitable for a wide range of patients, such as those with advanced stage diseases - stages 3 and 4 and patients who have an aggressive disease with a high risk of cancer recurrence.

"Patients who are diagnosed with cancer at an early stage and/or have high risk of cancer recurrence are the best candidates to undergo the treatment programme," points out Dr Ang.

The cost starts at S$5,000, and prices vary depending on the number of cancer anti-agents tested on the mice, he says. "For example, a typical patient may need to test three drug combinations. The cost for this patient will definitely differ from the cost of another patient who may want or need to test 10 different drug combinations," he points out, adding that the cost is secondary as compared to the benefits such as time saved and greater efficiency of treatment.

Dr Sidransky notes that the world is already doing "some form" of molecular personalisation for cancer patients, but in the next five years, graft-testing or a derivative will become a major part of the solution for cancer.

In Singapore, Dr Ang notes that the three biggest advancements of cancer treatments here are in the understanding of the molecular genetics of cancer, the capability of Singapore labs to make this commercially available for our patients, and the discovery and availability of many new targeted agents that are effective in treating carefully selected subgroups of cancer patients with specific mutations in their cancer.

uihoon@sph.com.sg