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Not the summer I expected

Posted by Ron Grunwald on 2013-06-05 - one comment

I'm excited about the beginning of the 2013 program! New faces, new sciences, new challenges. Of course, I expected that. What I didn't expect was that much of my summer would be taken up with chemotherapy. So, I'll be blogging about that.

Let's start with the cancer: Pure Seminoma. Never heard of before. Sounds like an advertising campaign for someplace in New Mexico or for a brand of medical marijuana. The good news is that it's a typically slow growing tumor, responsive to treatment. In other words, I expect to be cured by the end of the summer. If you have to get cancer, I recommend this one to you.

The interesting and somewhat surprising thing to me about my seminoma is that the diagnosis, and therefore treatment plan, is based almost entirely on the histology, i.e., what the cells look like under the microscope, and evidence of spread. It looks like the cells have metastasized to a lymph node, so technically I have Stage IIA seminoma = chemotherapy = no beard for the summer.

What surprises about this process, aside from the lack of beard, is that we know so much about cancer these days. A cancer is a cell gone wild, one that proliferates out of control from a tissue already set to proliferate like an epithelium (e.g., lining of the gut, lungs, mammary ducts), stem/progenitor cells (eg, bone marrow) or germ line (ovary, testes). The loss of growth control is know to be the result of a relatively small number of mutations that inappropriately active the proliferation pathways (oncogenes), disable the normal proliferation checkpoints (tumor suppressors), evade program cell death (anti-apoptosis), immortalize (telomerase), promote the blood supply to the tumor (angiogenisis), and liberate for metastasis (adhesion molecules). All of that was implied in my funky looking cells and their sojourn to the lymph node.

But looking at the genomes, for example, of breast and lung tumors, the average number of cancer causing mutations is around 11 per tumor. Not really that many changes at the DNA level. But they weren't necessarily the same 11 mutations in each lung cancer tumor. There are large number of possible targets in each of the functional classes (oncogenes, tumor suppressors, etc) of genes, so any given tumor may be the result a peculiar and unique collection of mutations.

In other words, I don't have "pure seminoma". I have Ron's seminoma, my own cancer, genetically unique with my special profile of mutations. And the particular mutations have implications for both the growth properties of my cancer cells and how they will respond to drugs. So, in principle, along with the histology and CAT scans and pregnancy tests (HCG is a serum marker for another more aggressive type of testicular cancer. Fortunately on both counts, I'm negative), we should be looking at my tumor genotype to decide the best course of treatment.

So why didn't I get my tumor genotyped? The cost of whole genome (exome) sequencing is almost low enough these days to be almost routine. The simple answer, in my case, is sort of good news: The typical outcomes for traditional chemotherapy with my diagnosis are so good (95+% cure rate) that cost of sequencing would be justified. And, for the same reason, even if we knew what my mutations are, there isn't really anything to do with that information. For this kind of cancer, there hasn't been a pressing need to find new drug targets that promise more effective cures. It's not that there isn't science to be done, it jthe economics that doesn't work out.

I'm at the end of my second cycle of therapy, and feeling pretty good this week. So I suppose for this blog I'll celebrate the low-tech approach to my treatment as a good thing. But next week I go back for one more cycle of my two poisons - etoposide and cis-platin - and two weeks of side effects. There are short term effect - the nausea, the decimated throat, the numbing fatigue and the knocked out immune system, not to mention the beard. And there are the long term side effects: increase risk of heart disease, increase risk of leukemia. So, no, I'm not really happy. I wish there was better, but I'll take what I can get.

Dr. G

Tagged: RF2013-Week1