Cancer is a disorder of genetic mutations, with some variations so resistant to medical intervention that a diagnosis for those forms of the disease verges on a death sentence.
B.C. has the best ovarian cancer outcomes in the world. Yet, the five-year survival rate barely tops 40 per cent. And only one in five Canadians diagnosed with some forms of lung cancer will live that long.
The numbers are beyond grim. But that may be about to change.
Genomics is already leading to forms of care that are individually tailored to both the patient and the precise genetic signature of the patient’s cancer. That’s because cancer is not a single foe, but comes in hundreds of unique varieties.
Marco Marra, researcher and director of the Michael Smith Genome Sciences Centre of the BC Cancer Agency, and Sam Aparicio, head of the Department of Breast and Molecular Oncology at the BC Cancer Agency, and Professor in the Department of Pathology and Laboratory Medicine at UBC, have documented 80 different types of an aggressive form of breast cancer, called triple negative, defined by the absence of three hormone receptors.
Triple negative breast cancers represent about 16 per cent of breast cancers and, until the BC Cancer Agency’s work, had been treated as a single disease, often with little success.
“The great advance of genomics is that we can now see how different they all are,” said Marra.
Marra and Aparicio also found that cells within a single breast cancer tumour may contain different mutations, thus creating a mosaic of cells all evolving independently that each respond to treatment differently.
That means drugs that kill cells with a specific mutation could easily leave other cancer cells unscathed to start new tumours. Cancer treatments would have to be targeted to the genome of all the cancer cells in a tumour to be effective, he said.
“It’s critical to use this information to start imagining how we can treat breast cancers,” said Marra.
“The idea that you can treat these very different entities with a (single) drug becomes questionable. When you are talking about a diverse community of cancer cells, one-drug therapy isn’t going to work.”
Marra likens the better approach to the drug “cocktails” used to treat HIV, in which each component is designed to attack in a different way.
While there are some forms of the disease that occur in people with specific genetic predisposition, cancers are often driven by “bad luck,” genetic mutations in cells that occur during a person’s lifetime and compromise the ability of DNA to repair itself, said Marra.
“Sometimes it’s a mistake that happens in a place where the cell can’t afford for there to be a mistake. When that happens, they accumulate DNA damage at an incredible rate.”
As the number of drugs that target specific cancer genes grows, doctors can sequence the DNA of the tumour to determine which drug or drugs have the best chance of success, minimizing unnecessary treatments and all the costs and discomfort that go with that.
By sequencing the whole genome of both the tumour and the patient, scientists can see where they are different and form a clearer picture of the pattern of mutations that cause the cancer.
“When we start to see which mutations seem to be important to the biology of those cancers, we start to find new ways to take advantage of the mutation,” said Marra.
In cases where a genetic mutation has caused production of a protein that is misshapen and harmful, new drugs might act to suppress its production.
“This is where most of the drug development is concentrated right now,” said Marra.
The BC Cancer Agency is leading a collaboration of 17 researchers who are sequencing the genome of malignant tumours in patients that have not been helped by conventional treatments, looking for common and unique features.
“In about 70 per cent of these cases, we learned something about the cancer that we had no idea was there and in many of those cases the oncologist was able to use that information to propose a targeted therapy,” Marra said.
“Often, we don’t need to invent a new drug, rather we use the patient’s profile to choose from what we have at our disposal currently.”