There are 50 or more different diseases called sarcoma, and in some of them many subtypes. As genetic studies have improved and become more easily done, it has become apparent that each of the different sarcomas has a genetic profile different than the others. That means that the genes that control cell proliferation, inhibiting it in some cases and helping it in others, seem to be different from one sarcoma type to another. In the human body there are more than 20,000 genes, and part of the problem is figuring out what causes what, and which genes are just there seemingly doing nothing. This genetics of cancer is not for the faint of heart.
Gene mutations happen to all of us as we go through life, and most of them are not significant. Telling insignificant gene mutations from the significant ones is one of the difficult problems in cancer, and specifically in sarcomas. For example, Brandon Moriarty Ph.D., talking at a recent conference noted that analysis identified over 200 known and novel osteosarcoma genes. Manish Parashar, quoted in the current issue of the Scientific American, states “we can collect data faster than we can do anything about them.” So the U of Minnesota has a computer scientist in bioinformatics working with the sarcoma researchers.
At a unique University of Minnesota Sarcoma Program Retreat held May 28th and attended by Sue and Pete, Kate Bottiger and myself, many scientists from the U gave talks about what they were doing in sarcoma. Major presentations and research findings were presented by Dr. David Largaespada, Dr. Amy Skubitz, Dr. Christopher Moertel, Dr. Edward Cheng, Dr. Subree Subramanian, Dr. Branden Moriarity, Dr. Logan Spector, Dr. Jaime Modiano, and Antonella Borgatti.
Osteosarcoma is very common in dogs, more so than in humans. There is a large inherited susceptibility in dogs, but not in humans. What do we do with that information? Veterinarians at the U are working with OS in dogs in hopes of finding a novel treatment that might transfer to humans. Synovial sarcoma in contrast to osteosarcoma, has a single gene abnormality. It remains to be seen whether treatment can be developed to be aimed at this single gene, and if it will be effective.
Sarcomas are heterogeneous, meaning there is just not one abnormal cancer cell type in the cancer. So chemotherapy that gets good necrosis rates may indeed be getting the easy cancer cells, leaving behind the ones that don’t respond. That was clearly the case for my granddaughter who had 97% necrosis (meaning death of cancer cells seen on tissue slides taken at the time of surgery) after initial chemo, then passed away a year later of cancer spread.
Lee Helman, from the National Cancer Institute, spoke at the meeting we went to and he said that multiple drug combination therapy would probably be necessary since rapid drug resistance occurs with single drug treatment. He also commented that single agent clinical trials were largely ineffective.
Where are we in this? It was easier to send a man to the moon!
And where does the money come from for research. If you were a Senator or Representative you would feel obligated to fund breast, lung, and pancreatic research for example because of the huge number of people involved by these cancers. A lot fewer people are afflicted by sarcomas, and it doesn’t get as much attention. And that’s where we come in.
John L. Seymour MD, RIS Board Member