Nature heavy anti-cancer research rollover? Large clinical trials have shown that intermittent use of anti-cancer drugs does not help melanoma patients!

May 14, 2020 News /BiovalleyBIOON / - target and block cell growth signals can be significantly reduced drug
a tumor, but the cancer often relapse

A study in mice showed dramatic seven years ago, if a cancer patient every few weeks to stop the medication, then these targeted drugs are better able to treat melanomaa However, the first large trials to test this idea found that when patients with such "intermittent" administration program, a recurrence of a melanoma fasterThe overall life of study participants nor longer than those taking conventional drugsthese disappointing results will soon be published in the annual meeting of the American Association for Cancer ResearchThese results give a large number of ongoing clinical trialsof a new strategy to fight cancer drug resistance poured cold water"There are many reasons to believe that this is feasible."tumorscientist at the University of California at San Francisco, led theAlainAlgazi melanomatrial, he said: "This is .....seems to be a very powerful idea"about a half of a patient in a melanoma of a gene called BRAF, comprising a mutant gene, this mutation generates a kinds of abnormal protein that promotes tumor growthMuteins blocking this drug is often only a few months so thattumorreduced, and resistant cells will take overThis resistance is not only the BRAF inhibitor "big problem", and other targeted cancer drugs is "a big problem."Source: BIOPHOTOASSOCIATESSCIENCESOURCEa study on mice published in Nature magazine in 2013 proposed a simple but counterintuitive solutionWhen researchers treating mice with melanoma with BRAF inhibitors, until their tumors begin to grow again, and then no treatment, the tumor shrinkageApparently it controlledresistant tumor cellshave come to rely on the drugWhen the rats were given intermittent drug - after a few weeks, stop, and then continue - their life is twice that of those taking the drug every day micethese animal data, plus some anecdotal reports of patients with a BRAF inhibitor resistancetumor growth or slow-down after stopping the drug, prompting the US National Cancer Institute (NCI ) more cancer centers in the United States and Canada to carry out intermittent dosing trial for a period of five yearsAbout 250 patients with advanced melanomapatients receiving both drugs BRAF inhibitors and MEK inhibitor combination therapy, the two drugs can block the growth of another protein in the same pathway206 patients in the first 8 weeks after receiving this combination therapy, tumor shrinkage or stabilization, is divided into two groups One group received daily medication until they tumor growth, and another set of drugs per day, for 5 weeks, three weeks of rest interspersed group in intermittent administration, patient's tumor started to grow again in an average of 5.5 months, compared with the continuous administration group 10 months "The results and forecast our expectations and contrary to all pre-clinical data," UCLA cancer researchers AntoniRibas said he is co-leader of the trial These two groups of patients, if tumor recurrence, most people will continue to receive immunotherapy drugs, but overall survival time is about the same - about 40% of patients were still alive four years later Algazi team provided several possible explanations to explain why the results of rat experiments in humans have not been verified The overall amount of medication that patients receiving intermittent therapy is no more (although the same is true in mice) patients the standard treatment group People metabolize drugs slower than mice, several animal studies indicate that the drug-dependent tumor cell death may require a sharp decline in drug levels In addition, "there may be different mechanisms of resistance in different patients," Algazi said (Mouse studies of 2013, a cell is typically a tumor drug resistance by increasing the BRAF protein is produced.) In a radiologist to see Moffitt Cancer Center RobertGatenby , the last explanation Algazi is justified His study reports that the surgeon can control the intermittent treatment on tumor growth by using a hormonal agent of prostate cancer - if simulate the evolution of the tumor growth by tracking for each patient and to the amount of tailored to the planned dose words "Any fixed schedule, such as NCI trial, apparently did not include the potential evolutionary force," Gatenby said other cancer researchers said NCI test method has not yet conclusive Memorial Sloan-Kettering Cancer Center, a cancer biologist at CharlesSawyers said: "I do not know whether this hypothesis has been fully verified." He believes that the half-life of a MEK inhibitor used in the test can be a problem tumor scientist at Oxford University in the UK MarkMiddleton co-chaired a similar melanoma test, using a different dosing regimen; expected later this year there results Middleton said the trials and other ongoing trials "will help us determine if special circumstances require intermittent treatment, or whether the idea failed." (Bio Valley Bioon.com) References: [1] On-offdosingofcancerdrugsdoesnothelpmelanomapatients Whenlessismore [2] [3] [4] Modellingvemurafenibresistanceinmelanomarevealsastrategytoforestalldrugresistance DabrafenibandTrametinibinTreatingPatientsWithStageIII-IVBRAFMutantMelanomaThatCannotBeRemovedbySurgery
[5] Zhang, J., Cunningham, JJ, Brown, JSetal Integratingevolutionarydynamicsintotreatmentofmetastaticcastrate-resistantprostatecancer NatCommun8,1816 (2017) https://doi.org/10.1038/s41467-017-01968-5