Cure Cancer? Not Without a Course Correction

[gdpawel]

Time to Research Oncology Treatments for Efficacy

The “war on cancer” devotes too much in search of new cures and too little to understanding the results of existing oncology therapies.

By the most objective measure of progress—improved overall survival—the results from the hunt for new cures are meager. “The age-adjusted mortality rate for cancer is about the same in the 21st century as it was 50 years ago, whereas the death rates for cardiac, cerebrovascular, and infectious diseases have declined by about two-thirds,” laments Harold Varmus, the Nobel Prize-winning cancer researcher and former head of the National Institutes of Health, in his otherwise upbeat assessment about the future prospects for cancer research.

This is why a redrawn battle plan—one that focuses on turning the treatment system into a research and learning system that can teach oncologists the best use of the weapons they already have—is long overdue. To understand why this shift in focus is essential, let first examine our record to date in hunting for new cures.

http://www.scienceprogress.org/2009/05/cancer/

[Rich66]

The dismal failure to fund something as broadly promising as the LIFT trial still makes me cringe when I see all the merchandise and "'thons" for cancer research. Soon I'm going to have to step into that massive American Cancer Society building here in Madison and see where the $$$ is going. There are so many institutions across the political spectrum that would benefit from major advances against cancer. I can't help but feel the ball is being dropped...probably just out of chos and lack of coordination. I have found researchers in the same university unaware of research peers that they sit on boards with are working on, even publishing.
But sheer volume of research may yield very little beyond incremental improvements.
Me thinks if cancer stem cells are the root of the problem, judging "success" by shrinkage (RECIST criteria) has led decades of research down the wrong path. CSCs could be the course correction needed.

[gdpawel]

Me thinks you may be right about cancer stem cells being the root of the problem.

Stem cells have that infinite ability to renew themselves and produce the many different cell types that make up a human. Cancer's hallmark is its ability to grow infinitely, multiplying into various cells that make up a tumor. Is cancer the result of a normal stem cell turned bad or an ordinary cell that somehow acquires a stem cell's immortality and versatility?

The recent finding that Temodar (temozolomide) increased the number of cancer cells with stem-like characteristics sounds eerily similar to the increase in the number of metabolic activity of mitochondria of the surviving cells from taxane (Taxol) therapy, even in cases where the majority of the cells are being killed by taxanes. It may indeed give clinical response (tumor shrinkage), however, these are mostly short-lived and relapses after a reponse to taxanes are often dramatic.

In stem cell research, anti-cancer treatments often effectively shrink the size of tumors, but some might have the opposite effect, actually expanding the small population of cancer stem cells that then are capable of metastasizing. Using the CellSearch System technique that quantifies circulating tumor cells, scientists had shown that chemotherapy with Taxol causes a massive release of cells into the circulation, while at the same time reducing the size of the tumor, explaining that complete pathologic responses do not correlate well with improvements in survival.

Circulating tumor cells (CTCs) are cancer cells that have detached from solid tumors and entered the blood stream. This can begin the process of metastasis, the most life-threatening aspect of cancer. To metastasize, or spread cancer to other sites in the body, CTCs travel through the blood and can take root in another tissue or organ.

Even before the advent of the CellSearch technique, it had been observed in Cell Function Analysis that there was an increase in the number of metabolic activity of mitochondria of the surviving cells from Taxol therapy, even in cases where the majority of the cells were being killed by Taxol.

This new research hightens the faults of gene amplificaton/mutation studies. Genetic profiling assumes that all drugs within a class will produce precisely the same effect, even though from clinical experience, this is not the case. Nor can genetic profiling tell anything about drug combinations.

Are you sure that you’ve identified every single protein that might influence sensitivity or resistance to drugs? The "cell" is a system, an integrated, interacting network of genes, proteins and other cellular constituents that produce functions. You need to analyze the systems' response to drug treatments, not theoretical predispositions.

Cancer is a complex disease and needs to be attacked on many fronts. Cellular profiling holds the key to solving some of the problems confronting the critical task of matching individual patients with the treatments most likely to benefit them.