"Long before it's in the papers"
February 29, 2016


Go-slow cancer treatment might actually work better, study suggests

Feb. 29, 2016
Courtesy of Science Translational Medicine
and World Science staff

Can we learn to live with­—rather than kill—can­cer?

A new study sug­gests fre­quent, low-dose chem­o­ther­a­py that keeps tu­mor growth un­der con­trol might work bet­ter than stand­ard high-dose chem­o­ther­a­py that aims to kill eve­ry can­cer cell.

The new ap­proach, which scientists tested in mice, flies in the face of con­ven­tion­al ther­a­py, which gen­er­ally hits pa­tients with the max­i­mum drug dose pos­si­ble to de­stroy the larg­est num­ber of tu­mor cells. But these ag­gres­sive treat­ments—though they may buy a good deal of time—tend to pro­duce a lot of tox­ic side ef­fects, and few real cures.

So some re­search­ers are look­ing at a new strat­e­gy. Their idea is that ag­gres­sive treat­ments might fail be­cause they leave alive only those hardy can­cer cells that are re­sist­ant to the drug be­ing used. And those can­cer cells, on their own, pro­lif­er­ate even faster than when they were along­side oth­er, slightly dif­fer­ent can­cer cells, be­cause the dif­fer­ent cell types com­pete and there­fore keep each oth­er some­what in check.

The al­ter­na­tive strategy, then, is to lim­it the treat­ment so that it does­n’t kill eve­ry can­cer cell that it could kill, but just most of them. In the stu­dy, Pe­dro Enriquez-Navas at the H. Lee Mof­fitt Can­cer Cen­ter and Re­search In­sti­tute in Tam­pa, Fla. and col­leagues de­signed such a treat­ment ap­proach, which they called an evolution-based or adap­tive ther­a­py.

They tested the ap­proach with the chem­o­ther­a­py drug pa­cli­taxel in mice with two dif­fer­ent types of breast can­cer. Stand­ard chem­o­ther­a­py shrunk the mouse breast tu­mors, but only to have them grow back as soon as treat­ment stopped. Anoth­er treat­ment reg­i­men that skips doses when­ev­er the tu­mor shrunk al­so in­evitably led to tu­mor pro­gres­sion, the re­search­ers said.

In con­trast, the evolution-based ther­a­py was more ef­fec­tive in con­trolling tu­mor growth than ei­ther stand­ard ther­a­py or dose skip­ping, they found. The new strat­e­gy con­sisted of high in­i­tial drug doses fol­lowed by pro­gres­sively low­er doses as the tu­mor re­sponded.

In fact, the in­ves­ti­ga­tors said, the treat­ment al­lowed them to wean more than half the mice off the drug com­pletely, with­out re­laps­ing for a few weeks (which could be much long­er in hu­man time, since mice tend to live less than two years).

Co-researcher Rob­ert A. Gatenby, al­so at the Can­cer Cen­ter, said that al­though some pos­i­tive re­sults were ex­pected, the sci­en­tists don’t un­der­stand why the treat­ment worked so well that it could be sus­pended al­to­geth­er.

“The find­ing that the tu­mor, once con­trolled, re­quired rel­a­tively lit­tle treat­ment to main­tain con­trol was a sur­prise since it was not pre­dicted by the math mod­els and sug­gests we have not fully ac­counted for all of the im­por­tant un­der­ly­ing dy­nam­ics,” he said in an e­mail.

“We do plan to in­ves­t­i­gate this fur­ther in the fu­ture al­though for pur­poses of ap­ply­ing this work to clin­i­cal can­cer pa­tients our main fo­cus re­mains on the dif­fi­cult task of gain­ing con­trol of the tu­mor which is in­i­tially grow­ing rapid­ly.”

The findings are pub­lished in the Feb. 24 issue of the jour­nal Sci­ence Trans­la­tion­al Medi­cine.

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Can we learn to live with—rather than kill—cancer? A new study suggests frequent, low-dose chemotherapy that keeps tumor growth under control might work better than standard high-dose chemotherapy that seeks to kill every cancer cell. The new approach, which the researchers tested in mice, flies in the face of conventional cancer therapy, which generally hits patients with the maximum drug dose possible to destroy the largest number of tumor cells. But these aggressive treatments—though they may buy a good deal of time—are usually much better at producing toxic side effects than complete cures. So some researchers are looking at a new strategy. Their idea is that aggressive treatments might fail because they leaves alive only those cancer cells that are resistant to the drug being used. And those cancer cells, on their own, proliferate even faster than when they were alongside other, slightly different cancer cells, because the different cell types compete and therefore keep each other somewhat in check. The alternative idea, then, is to limit the treatment so that it doesn’t kill every cancer cell that it could kill, but just most of them. In the study, Pedro Enriquez-Navas at the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Fla. and colleagues designed such a treatment approach, which they called an evolution-based or adaptive therapy. The researchers tested the approach with the chemotherapy drug paclitaxel in mice with two different types of breast cancer. Standard chemotherapy shrunk the mouse breast tumors, but only to have them grow back as soon as treatment stopped. Another treatment regimen that skips doses whenever the tumor shrunk also inevitably resulted in tumor progression, the researchers said. In contrast, the evolution-based therapy was more effective in controlling tumor growth than either standard therapy or dose skipping, they found. The new strategy consisted of high initial drug doses followed by progressively lower doses as the tumor responded. In fact, the investigators said, the treatment allowed them to wean more than half the mice off the drug completely, without relapsing for a few weeks (which could be much longer in human time, since mice tend to live less than two years). Co-researcher Robert A. Gatenby, also at the Cancer Center, said that although some positive results were expected, the scientists don’t understand why the treatment worked so well that it could be suspended altogether. “The finding that the tumor, once controlled, required relatively little treatment to maintain control was a surprise since it was not predicted by the math models and suggests we have not fully accounted for all of the important underlying dynamics,” he said in an email. “We do plan to investigate this further in the future although for purposes of applying this work to clinical cancer patients our main focus remains on the difficult task of gaining control of the tumor which is initially growing rapidly.” suggests