Colon and Rectal Cancer: The Myth of 2 Beasts
Colon and Rectal Cancer: The Myth of 2 Beasts
Hello. I'm David Kerr, Professor of Cancer Medicine at the University of Oxford and Past President of the European Society for Medical Oncology. Today I would like to talk a little about the molecular characterization of colorectal cancer.
There has been a huge amount of work done in this area. Perhaps the most important recent paper has just been published in Nature by the Cancer Genome Atlas Network, a huge consortium. They were very well funded by the National Cancer Institute to do almost industrial-strength genetics to try to unpick and take apart the genetic coding that characterizes sporadic -- the common type -- of colorectal cancer. They looked at about 275 colorectal cancers and looked at exome sequencing, microRNA, and almost everything that they could.
They have come up with some rather interesting findings. Perhaps the most interesting to me was that colon and rectal cancer are genetically virtually indistinguishable. This puts to rest a mythology that has been promulgated throughout my world of gastrointestinal cancer that rectal and colon cancer are somehow different beasts that need to be looked after and therapeutically managed in different ways. But there is no molecular basis for that whatsoever. They have put that mythology to bed.
Another interesting finding was that there were about 24 common mutations, and they separated into 2 distinct pathways: one around hypermutation and microsatellite instability (about 15% of colorectal cancers) and the other around chromosomal instability. Apart from the usual suspects -- mutations that we know about in p53, RAS, and SMAD -- there were some interesting observations around fusion proteins with the WNT pathway. It does look as if MYC is an important transcriptional control in terms of conducting how the colorectal cancer cell responds. There were 2 interesting pathways around ERBB2 and amplifying IGF2 that may signal or point to a direction in which we may go with targeted therapies. But it's stamp collecting. It's a business that I'm in myself. It's one that I love. It's that seeking to understand the molecular biology of the disease.
Although we have much deeper information, in a genetic sense, about colorectal cancer, it's still in a relatively small cohort of 275 patients. Therefore, in order for us to link the genetic pathway analysis to clinical behavior, we need much larger sample sets to be able to get a real feel for the biology. This is an interesting piece of stamp collecting. It tells us that colon and rectal cancers are the same. Phew, because I had always believed that. It's giving us some very early pointers as to where we might start to develop some new ideas for therapeutic intervention.
We are in the very early days. We need to expand the cohort significantly to make the link between biology and behavior, between genotype and phenotype. Let's get on with doing some larger, collaborative studies.
Hello. I'm David Kerr, Professor of Cancer Medicine at the University of Oxford and Past President of the European Society for Medical Oncology. Today I would like to talk a little about the molecular characterization of colorectal cancer.
There has been a huge amount of work done in this area. Perhaps the most important recent paper has just been published in Nature by the Cancer Genome Atlas Network, a huge consortium. They were very well funded by the National Cancer Institute to do almost industrial-strength genetics to try to unpick and take apart the genetic coding that characterizes sporadic -- the common type -- of colorectal cancer. They looked at about 275 colorectal cancers and looked at exome sequencing, microRNA, and almost everything that they could.
They have come up with some rather interesting findings. Perhaps the most interesting to me was that colon and rectal cancer are genetically virtually indistinguishable. This puts to rest a mythology that has been promulgated throughout my world of gastrointestinal cancer that rectal and colon cancer are somehow different beasts that need to be looked after and therapeutically managed in different ways. But there is no molecular basis for that whatsoever. They have put that mythology to bed.
Another interesting finding was that there were about 24 common mutations, and they separated into 2 distinct pathways: one around hypermutation and microsatellite instability (about 15% of colorectal cancers) and the other around chromosomal instability. Apart from the usual suspects -- mutations that we know about in p53, RAS, and SMAD -- there were some interesting observations around fusion proteins with the WNT pathway. It does look as if MYC is an important transcriptional control in terms of conducting how the colorectal cancer cell responds. There were 2 interesting pathways around ERBB2 and amplifying IGF2 that may signal or point to a direction in which we may go with targeted therapies. But it's stamp collecting. It's a business that I'm in myself. It's one that I love. It's that seeking to understand the molecular biology of the disease.
Although we have much deeper information, in a genetic sense, about colorectal cancer, it's still in a relatively small cohort of 275 patients. Therefore, in order for us to link the genetic pathway analysis to clinical behavior, we need much larger sample sets to be able to get a real feel for the biology. This is an interesting piece of stamp collecting. It tells us that colon and rectal cancers are the same. Phew, because I had always believed that. It's giving us some very early pointers as to where we might start to develop some new ideas for therapeutic intervention.
We are in the very early days. We need to expand the cohort significantly to make the link between biology and behavior, between genotype and phenotype. Let's get on with doing some larger, collaborative studies.
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