New Wrinkle in Cancer Growth Precept

David J. Kerr, CBE, MD, DSc, FRCP, FMedSci


April 28, 2016

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Hello. I'm David Kerr, professor of cancer medicine at University of Oxford.

I'd like to discuss today a really interesting editorial that's just recently been published in the Journal of the National Cancer Institute by a close friend and colleague of mine, Francesco Pezzella.[1] What he does is challenge one of the basic hallmarks of cancer. We know that Judah Folkman declared in the early 1970s[2] that cancer growth must be preceded by angiogenesis, that there can be no increase in cancer bulk or burden without new vessels dividing, sprouting, supporting, and oxygenating the growth of the cancer, these cancer nodules.

Indeed, angiogenesis has become one of the classic hallmarks of neoplasia, and there are by now a variety of drugs—bevacizumab, ramucirumab, and the tyrosine kinase inhibitors—that seek to prevent new angiogenesis. What Francesco talks about is a different model in which there are some tumors. This is first noted in non–small cell lung cancer[3] and pulmonary metastases, which are nonangiogenic. Rather than requiring the proliferation of new blood vessels, it seems that there are some tumor cells that are capable of co-opting existing blood vessels within organs such as the lungs and liver.

This is a new process, probably an active process. It's probably cell surface adhesion molecule driven. But there are no clear ideas as yet as to what, mechanistically, the key events are. Of course, this poses a really huge number of really interesting questions. Is it possible that bevacizumab-resistant or ramucirumab-resistant tumors are those which switch from being angiogenic to nonangiogenic, thus devising and developing blood supply through co-option rather than new blood vessel formation?

If we understood more about the mechanism of action, it would lend itself to further drug targeting. If we combined an inhibitor of angiogenesis with an inhibitor of vascular co-option, would it prevent the outgrowth of resistance to the existing antiangiogenic drugs, which are used widely in clinic?

This is a fantastic new area of science, requiring much mechanistic work. It is not yet another hallmark of cancer but one for which I think, over the coming 5-10 years, we'll see increasingly focused research, more mechanistic insights, and perhaps—if we're lucky—an idea that can be used on development pathways.

As always, thanks for listening. Have a look at the article; ponder it. In a way, it should come as no surprise. But here we are, rationally challenging one of the hallmarks of cancer that is among the great precepts introduced by one of the all-time great cancer biologists, Judah Folkman.

I'd be very interested in your comments, grateful for anything that you might care to say or add. In the meantime, Medscapers, ahoy—over and out. Thank you.


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