Decoding the genome will transform medicine: experts

From left, Karen Malkin-Lazarovitz and scientists Sarit Assouline and Ido Amit take part in a discussion on the hope for “personalized medicine” through greater understanding of the human genome.

MONTREAL — Karen Malkin-Lazarovitz didn’t think twice about what to do when she learned she carried a BRCA genetic mutation. With several family members having had either breast or ovarian cancer, the young mother knew the odds were overwhelmingly against her escaping disease, and it would probably come at an early age.

Four years ago, the mother of two children, then age four and 18 months, began the lengthy and arduous process of having both a double mastectomy and a hysterectomy.

She did not have cancer; the surgery was prophylactic. Today, she is well – and has no regrets whatsoever about her decision.

Malkin-Lazarovitz was a panellist in a recent discussion sponsored by Weizmann Canada on “Personalized Medicine,” that is, customizing treatment to the individual based on their genetic makeup.

The two scientists participating, one from the Weizmann Institute of Science in Israel, the other from the Jewish General Hospital (JGH), believe that, in the coming years, doctors will be able to prescribe “the right drug, in the right dose, at the right time.”

Understanding the human genome will open the door to new means of diagnosing, predicting and possibly preventing disease, said Weizmann immunologist Ido Amit, who acknowledged that the genome remains “a huge puzzle to solve.”

More than 20 years after the launch of the Human Genome Project to map the billions of genes each person carries, the number of genes completely decoded remains in the thousands.

However, that knowledge was enough to help people like Malkin-Lazarovitz decide what to do. Genetic testing revealed that she had an 87 per cent chance of getting breast cancer and about 50 to 60 per cent of contracting ovarian cancer.

“A lot of people said to me, ‘Wait.’ They can treat cancer, but with my broken genetic code, it would come back,” Malkin-Lazarovitz said. “I’m not a gambler… I know I’ve done everything to see my kids grow up.”

Amit, who returned to Israel last year after several years at Harvard University, said that cancer is still being treated with a “sledgehammer,” referring to non-targeted drugs that act on the whole body, often harmfully, not just on the tumour.

The treatment is usually the same for the same cancer, he said, without regard for the individual’s unique genetic makeup.

Sarit Assouline, a clinical researcher in the JGH oncology and hematology department, said the hospital’s Segal Cancer Centre is one of 16 cancer research centres in 13 countries taking part in Worldwide Innovative Networking (WIN).

She described this as a unique project that is trying to find out if U.S. FDA-approved drugs may be used for other cancers than those for which they are intended, or can otherwise be tailored to the individual.

Two hundred people with advanced cancer, who have relapsed on standard therapies, are being recruited for a clinical trial.

They will undergo biopsies of both their tumour and their normal tissue.

Knowing the genetics of the tumour itself may be helpful in tailoring treatment, said Assouline, who as a teen was selected for Weizmann’s international summer science program.

In about 40 per cent of cases, cancer is associated with a genetic mutation, including chronic leukemia, which is Assouline’s speciality. That type of blood cancer does respond well to one of the early gene-targeting drugs, Gleevac, developed at Weizmann. The problem is it must be taken for life, and a typical dosage costs $3,500 a month in Canada. The role of genetics in the development of cancer is clearer to scientists than its role in many neurological or other disorders, such as Parkinson’s or schizophrenia, Amit said.

He pointed out that genes not only mutate, but can translocate, that is, join together, a fact that also has implications for health.

During the question period, both scientists agreed that knowing your genetic susceptibility to specific diseases raises ethical questions, such as whether insurance companies could refuse to provide coverage.

Perhaps surprisingly to the layperson, Amit thinks personalized medicine will face a lot of resistance from the medical profession, but ultimately doctors will have to meet the demands of patients.

For Malkin-Lazarovitz, her wish is that by the time her five-year-old daughter is an adult, science will know more about fixing genetic mutations.

“If not, I hope she will not be afraid of her options, that she will see that I got through it.”