>If you made me cancer dictator with an NIH budget and an ability to set the rules I could provide very rapid progress.
What would you change?
What would you change?
1. Demand we use animal models that reflect actual human disease (natural occurrence in old age). No more sticking human cancers cell lines into SCID mice.
2. Genome sequence all human cancers so that we classify them by genetic defects. We should not care which tissue a cancer arose in, but by which drugs it is selectively sensitive to.
3. Test new treatments in patients that reflect actual patients - ie newly diagnosed patients, not patients that are weeks away from dying and who have failed everything else.
4. Go all out on the immune approach with an emphasis on developing treatments with minimal side-effects that can be given to healthy people as a preventative treatment. We need to think about cancer as something we prevent rather than cure.
2) There's already significant efforts underway to sequence many thousands of human tumors (e.g. you probably know about TCGA). Once the cost drops a bit more, then it might be feasible to sequence all tumors. However, a pathologist can still tell you quite a bit that's hard to reverse-engineer from sequencing (e.g. does the cell look like a melanocyte?). Classifying by tissue of origin (+ the ontology of cancer subtypes) does actually capture a lot of the variation between cancers. Sequencing adds a little on top of that, but surprisingly not as much as people hoped. For example, how often can you predict actionable drug sensitivity from RNAseq or WES? In my experience so far, there's only even the possibility of clinical benefit in a small number of special cases (e.g. BRAF V600E).
3) Newly diagnosed patients often have great treatment options! Do you really want to RCTs with placebo arms on stage I breast cancer patients?
4) "Go all out on the immune approach" there's been a huge boost of funding in that direction (by the NCI/NIH and private donors like Sean Parker).
"with an emphasis on developing treatments with minimal side-effects that can be given to healthy people as a preventative treatment." That's an interesting idea and I don't know who's working on it. Write it up as a grant proposal and send it to the CRI?
1. Basically yes, although I would centralise the breeding of mice and then farm them out to researchers as they developed each of the different cancers. Another option that we are not making as much use of as we can is natural cancer in human pets. We have millions of dogs and cats developing natural cancers that we could use.
2. Yes sequencing has not shown the promise for treatment that we hoped, but that is because the treatments we have were not developed with genomic data. It doesn't matter how much you know about a cancer if you don't have any tools to actually attack the weaknesses identified. We need to use the genomic data to indentify weaknesses, then use these identified weaknesses to screen for new treatments.
The best targets will be those genes that are not normally expressed in adult tissue that are expressed in cancer tissue. When I was an academic I had a student look into this area and there are literally hundreds of genes that are regularly expressed in cancer that are not expressed in adults. These are perfect targets for immune treatments provided you have enough of them to draw on.
3. Actually most newly diagnosed patients have deceptively great treatment options. For most cancers most of our treatments are just delaying tactics, not curative. Anyway for those few cancers where we have great curative cancers treatments are not the areas that I would start on.
4. Many people have tried to get funding in this area without success. You appear to know something about the funding process so you would know that any such grant would fail to get funded. Because of the needs for a proper animal model infrustucture it would not be possible to do anyway. I would rather concentrate on getting the animal models right before working on any new treatments.
I am actually a former tenured academic scientist in the School of Pharmacy and Applied Science at Latrobe University here in Australia. I currently run a genomics software company (Nucleics). Cancer is one area I have had an active research interest in over the years and have thought a lot about these questions. While I may be wrong I hope I am not a dummy.
We really need to organise all the pets into clinical trials of new treatments. People have done surveys of pet owners and most people are happy for their pet to participate in such trials especially if they know that they are helping human research and other pets. We just need to start using this amazing resource rather than giving mice artificial cancers.
As for why more research has not come out of China, a lot of really interesting research is going on right now in China, it will just take a little time to filter out to us in the west. Drug development is a 15 to 20 year journey and China has only recently entered this domain.
1. http://vetmed.illinois.edu/translational-cancer-research-ben...