“Translational research” is the term used to describe the application of basic knowledge about cancer (basic research) into practical use for patients (the “clinic”). Earlier in the summer I started to write a post about why this is so difficult along with various misconceptions about breast cancer. I don’t need to finish writing most of that piece because there’s an excellent article in Newsweek on the history of cancer research, its impact on patients, and current trends.
…”There was nothing coming out of the basic science that could help” patients. In the high-powered labs funded by the war on cancer, molecular biologists thought they could change that. By discovering how genetic and other changes let cancer cells multiply like frisky rabbits, they reasoned, they could find ways to stop the revved-up replication at its source. That promised to be more effective, and easier on healthy cells than chemotherapy drugs, which also kill normal dividing cells, notably in the gut, bone marrow, mouth and hair follicles… In the 1970s and 1980s they discovered human genes that, when mutated, trigger or promote cancer, as well as tumor suppressor genes that, when healthy, do as their name implies but when damaged release the brakes on pathways leading to cancer.
It made for a lot of elegant science and important research papers. But it “all seemed to have little or no impact on the methods used by clinicians to diagnose and treat cancers,” wrote Harold Varmus, former director of NCI. Basic-science studies of the mechanisms leading to cancer and efforts to control cancer, he observed, “often seemed to inhabit separate worlds.” Indeed, it is possible (and common) for cancer researchers to achieve extraordinary acclaim and success, measured by grants, awards, professorships and papers in leading journals, without ever helping a single patient gain a single extra day of life. There is no pressure within science to make that happen. It is no coincidence that the ratio of useful therapy per basic discovery is abysmal. For other diseases, about 20 percent of new compounds arising from basic biological discoveries are eventually approved as new drugs by the FDA. For cancer, only 8 percent are.
There’s a lot more in the article, too. Only things missing that I think might be helpful are breast cancer specific information and misconceptions like some basics about breast cancer staging and differences related to prognosis and treatment depending on stage and other characteristics of an individual’s cancer. I still might write a little more on this some day.
(Nothing new about Laura recently.)
1 response so far ↓
1 Irene Bosch // Sep 13, 2008 at 8:45 am
Personalized Medicine
I read the article David pointed out.
I also found it very well written and with many useful epidemiological data about incidence of cancers, rate in which patients enroll in clinical trials, and success rates of chemotherapy, etc which added value to that article.
Thanks for pointing it to us.
One of the conclusions in the article is that due to the complexity of the makeup of the cancer cells, the individual’s genetic diversity, there is an approach for having a more personalized cancer treatment, specially designed for each patient.
I personally believe that is a good hypothesis. If we had good means to understand each patient-cancer biology, and with some good anti-tumor therapies in hand, there may be a chance to apply combinatorial strategies at once to destroy a particular tumor’s condition.
Maybe we should think about treating cancer’s condition, in the context of the immune system and genetics of each patient, instead of treating a cancer type.
One striking information was the one referring the proportion of patients that enroll in clinical trial with a 80-to 1-% differences between pediatric cases and adult cases.
That would be a big problem as clinical studies are necessary to move forward adult cancer therapies.
We scientist, indeed are still in the Stone Age of molecular biology when it comes to understand cellular physiology and mechanisms of malignancies. We are only scratching the surface of what it certainly is a big unknown cell machinery and mechanism. There are at least 40,000 proteins at a given second interacting in permutations of possible ways. David can help to get the number of interactions that are possible at one given time.
There are cell compartments that also control the function of those thousands of proteins.
The “control tower” or the nucleus of cell, may have failures with catastrophic consequences which can be permanent, in the case of genetic mutations. Or transient, a external stimuli, that will revert and chance the normal responses of a cell. The combination of “permanent” and “transient” changes is what is understood as a personalized mechanism of a cancer. Also, we would need to know exactly, what goes on in the particular individual’s normal cells in addition to what is occurring in the uncontrolled cells. And how each other interact in the context of that person.
My two good friends Katherine Martin and Marcia Fournier, had come up with a combinatorial signal detection that allows to predict outcome in breast cancer patients. It could be used to check the tumor response in each patient. Marcia took cancer cells and grew them in three-dimensions rather than in plates, to better resemble what happens in the body, where cells acquire a three-dimensional distribution in the breast. Doing that Marcia Fournier found that by growing cells in gelatinous conditions, the genes expressed were different than in two-dimensions. They used those genes to then look into clinical data bases of remission and not remission cases. And they built a group of genes that segregated in those two groups of outcome. Having such segregation they propose to use those genes to “predict” outcome.
Marcia and Kathy are very active and they both work closely to my research in virus infections. I am applying many of such tools used in cancer research to help move along infectious diseases research.
But this cost a lot of time and resources.
Federal support to scientific research is not going up in order to support new approaches and technologies. If we had a mandatory 10 cents of each dollar spent on war initiatives, for example, the last few years would have been the most important decade in the funding history of scientific research.
In the meantime, we will always keep optimistic, work hard and be inspired to find new diagnostics, and new approaches to help cure patients. And we will succeed as the very competent, intelligent, inspired, perseverant people join in choosing these kinds of scientific careers.
The open access Journal PLOsONE issue of August 2008 published the work of Marcia and Kathy. And if you would like to know more about their work, you can always email them at kjm@bioarray.us
Irene.