Breaks in chemotherapy enhance its effectiveness
Melanoma was cured after a time
Moreover, American scientists managed to increase the effectiveness of the drug without its additional modification or increasing the dosage.
In the latest issue of the journal Nature, a group of researchers from Switzerland and the USA announced a discovery that, in principle, can significantly prolong the life of patients suffering from one of the forms of melanoma – skin cancer – in its last, inoperable metastatic stage (Thakur et al., Modeling vemurafenib resistance in melanoma reveals a strategy to forestall drug resistance). In experiments on mice, they found that for a tumor whose cells become resistant to one of the anti-cancer drugs, this drug works much more effectively if you take breaks in treatment.
Melanoma is the most aggressive and deadly of skin cancers, which can be treated, as a rule, only at an early stage. About forty thousand people die from it every year. The life of a patient with metastatic melanoma is usually measured in months.
In more than half of cases, this disease is associated with a mutation of the BRAF protein gene. In August 2011, the U.S. Food and Drug Administration approved the drug Zelboraf (working name – vemurafenib), which suppresses the activity of the mutated BRAF protein and in most cases leads to a reduction of tumors.
The community of oncologists was very enthusiastic about the appearance of this drug, but then it turned out that not everything was so simple: in most cases, the cells of the shrinking tumor developed resistance to vemurafenib and began to multiply, ignoring the drug. At the same time, the number of BRAF cancer proteins began to grow rapidly. The same effect of the emergence of drug resistance to vemurafenib was found in laboratory experiments on mice.
Trying to determine the mechanism of this resistance, researchers from the University of California San Francisco and the Institute of Biomedical Research of Novartis came to the conclusion that in addition to resistance, tumor cells also develop addiction to the drug, becoming a kind of "vemurafenib addicts". Instead of hindering the growth of BRAF proteins, vemurafenib began to promote their appearance. And then, together with colleagues from the Zurich University Clinic, scientists developed a tactic of "intermittent" therapy, in which mice with drug-resistant tumors were given a "vacation", temporarily stopping injections of vemurafenib. And this tactic proved to be effective.
The schedule was as follows: a month of "cumulative" injections of the drug, a two-week break, then everything again. The researchers found that stopping injections of vemurafenib again caused tumor shrinkage in such mice and prolonged the life of the experimental rodents. If the mice from the control group, for whom no vacations were made, lived no more than a hundred days from the start of treatment, then the mice who received "medicinal vacations" lived at least 200 days.
Martin McMahon, professor Emeritus of cancer biology, who leads the team from the University of California, calls the revolutionary treatment of certain types of melanoma with vemurafenib. "However, the effectiveness of the drug," he says, "proved to be short–lived, since its use caused drug resistance to it in tumors. The method of intermittent therapy developed by us allowed prolonging its effectiveness and significantly prolonging the lives of sick mice."
The researchers believe that the same approach can prolong the effect of the drug for humans, but this idea should still be tested in future clinical trials.
Portal "Eternal youth" http://vechnayamolodost.ru10.01.2013