By Matt Jones
NEW YORK (GenomeWeb News) – The Ontario Institute for Cancer Research is conducting a cancer tumor resequencing and analysis project that seeks to serve as a framework for how sequencing may be used in the clinic to develop tailored cancer therapies.
OICR said yesterday that the study is based in part on sequencing that currently is being conducted by the International Cancer Genome Consortium, which has shown that some mutations associated with one type of cancer, such as the BRAF mutation, have been observed in other types of cancer.
"This suggests that cancer diagnosis should involve an in-depth analysis of a tumor's mutation for many different types of cancer, regardless of where the tumor originated," OICR said.
OICR President and Scientific Director Tom Hudson told GenomeWeb Daily News today that the institute's recent sequencing projects have been building up the foundation for this large-scale clinical sequencing project.
"We have actually already started clinical resequencing of patients with metastatic disease, resequencing a large number of target genes with the [Pacific Biosciences] system," he said, adding that those projects have been "testing the feasibility of moving to a large-scale study."
The aim of this effort is to conduct "molecular profiling by sequencing, as opposed to genotyping, actionable genes and cancers, so that we can move patients to the right clinical trials."
The ideas underpinning the new study were laid out by Hudson and other authors in a paper published in the Feb. 3 issue of the journal Cell.
The paper covers a number of the issues related to using genome sequencing in cancer trials, including tissue requirements, patient recruitment and informed consent, data sharing, and the implications of such projects and data on drug development, regulatory agencies, patients, providers, and others. It offers proposals and shares practices based on lessons OICR researchers have learned in trying to incorporate sequencing in cancer care and clinical trials.
"This framework is not about simply doing a new test but creating evidence that would inform what type of treatment would be given to individual patients," Janet Dancey, leader of OICR's High Impact Clinical Trials Program and lead author on the paper, said in a statement. "We currently have a strong theoretical basis but now we need to create evidence from clinical trials to put these theories into clinical practice."
"Based on our experience, we felt that we could suggest what should be done in the next five years, not just here but networking with the other big centers," Hudson told GWDN.
The study, which implements that framework, is a multi-center trial conducted with Princess Margaret Hospital involving five cities in Ontario and an initial 50 patients, Hudson said. The samples from these patients were sequenced on the PacBio system, and the analyzed information was spread by OICR among the clinical trials already happening in the province.
To add genome sequencing and analysis into patient care and clinical trials requires that the work happen swiftly, Hudson explained.
"We needed to be able to incorporate genomics within three weeks. After seeing the patient that is being asked to participate in the study, we have three weeks to get the DNA, go do the sequencing on the next-generation platform, report back the results, [and] get an expert committee, and we have been able to do that," he said.
One of OICR's central goals with this project is to use sequencing to test for a range of mutations in tumors, instead of just one type that has already been shown to have a meaningful association with treatment or outcome.
"There are many possible mutations that can be found, generally they are a low-frequency, although BRAF mutations for melanoma, we see those mutations in many other types of cancers," he said. "We don't think that there is a melanoma-specific cancer panel, or colorectal-specific cancer panel.
"We believe you need to look at all cancer genes in all cancer patients. The way to show which mutation responds to which drugs and which tumor types is actually going large scale," Hudson said. "Most of those mutations exist in multiple kinds of cancers, and it is time to think of knowing how to apply them across tumor types as opposed to single tumors."
Hudson also said that the data-sharing plans OICR is developing for this and other similar projects will be critical to its success, because the power of the clinical sequencing efforts for all of these variants is going to come through the scale of the project and the multi-site capability to access the genomic data of the patients and their outcomes.