Cancer Medicine

Why Petri dish studies don’t always translate into benefit for patients

Abel explains, in the first part of a promised series.

This is a topic I’ve been meaning to write about for a long time but somehow never got around to it. Abel explains nicely the barriers to drug absorption, distribution, and activity and why it’s very bad science for alties to try to extrapolate from studies of cells cultured in dishes to humans. In fact, toxicity to cultured cancer cells correlates only weakly with efficacy in an actual human, thanks to many of the factors Abel explains.

I would also point out that I’m involved as a coinvestigator in the evaluation of a drug that actually requires quite high concentrations inhibit tumor cell growth in a dish, levels higher than can be achieved in an experimental animal; yet this drug actually does inhibit tumor growth in xenografts implanted in nude mice. We suspect that it is because the drug disrupts a feedback loop wherein the tumor cells secrete a factor that stimulates themselves to grow and that this feedback loop doesn’t exist in cell culture. In any case, by strict pharmacokinetics, our drug would be considered unlikely to work in vivo, but preliminary experiments suggest that it does. Another example is angiogenesis inhibition. Most angiogenesis inhibitors do little or nothing to tumor cells in a cell culture dish. That’s because the tumor cells are not their target, but endothelial cells that form new blood vessels are. Angiogenesis inhibitors prevent these cells from forming new blood vessels for tumors, thus “starving” the tumor of nutrients and oxygen. These agents would never have been discovered if we relied on their activity against tumor cells in dishes to guide us.

By Orac

Orac is the nom de blog of a humble surgeon/scientist who has an ego just big enough to delude himself that someone, somewhere might actually give a rodent's posterior about his copious verbal meanderings, but just barely small enough to admit to himself that few probably will. That surgeon is otherwise known as David Gorski.

That this particular surgeon has chosen his nom de blog based on a rather cranky and arrogant computer shaped like a clear box of blinking lights that he originally encountered when he became a fan of a 35 year old British SF television show whose special effects were renowned for their BBC/Doctor Who-style low budget look, but whose stories nonetheless resulted in some of the best, most innovative science fiction ever televised, should tell you nearly all that you need to know about Orac. (That, and the length of the preceding sentence.)

DISCLAIMER:: The various written meanderings here are the opinions of Orac and Orac alone, written on his own time. They should never be construed as representing the opinions of any other person or entity, especially Orac's cancer center, department of surgery, medical school, or university. Also note that Orac is nonpartisan; he is more than willing to criticize the statements of anyone, regardless of of political leanings, if that anyone advocates pseudoscience or quackery. Finally, medical commentary is not to be construed in any way as medical advice.

To contact Orac: [email protected]

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