patients with the type of lung cancer more deadly may benefit in the future of a therapy that combines a new drug class with two other drugs already approved. In a study carried out in mice and human cancer cells the above combination has been shown to significantly reduce lung tumors.
The report, published in "Science Translational Medicine" and performed at the Institute of Francis Crick and the Institute of Cancer Research, London (Great Britain), has analyzed the inhibitors of G12C KRAS , a new family of drugs that is addressed to a specific mutation in the KRAS gene that can cause the cells to multiply without control and causing an accelerated growth of cancers.
These mutations, explain the researchers in their work, is found in 14% of the adenocarcinomas of the lung , the most common form of lung cancer. Unfortunately, there are still no effective treatments for most patients, and most of eight out of every ten will die at five years following diagnosis.
The drugs targeted to mutations G12C KRAS show promising antitumor activity and few adverse effects in clinical trials of EE. UU., but it is not clear how long a response before the cancer can become resistant
inhibitors of the mutant form G12C KRAS represent a major advance in the treatment of 14% of patients with lung cancer, says ABC HEALTH researcher Spanish Miriam Molina-Arcas, scientific senior research laboratory Francis Crick. "The results of the first clinical trials have been very encouraging; however, the experience with other inhibitors, such as inhibitors of BRAF in melanoma, suggests that tumors can become resistant to treatment. Our study has advance to this problem, and proposes a combined therapy that may improve the response to inhibitors of G12C KRAS and at the same time prevent the emergence of resistance."We found a combination of three drugs able to reduce this type of lung tumors in mice and human cancer cells
"it Is likely that the tumors develop resistance to the new drugs, so we must go ahead", explains the lead author, professor Julian Downward , who led the research. "We found a three-drug combination able to reduce this type of lung tumors in mice and human cancer cells".Our study has advance to this problem, and proposes a combined therapy that may improve the response to inhibitors of G12C KRAS and at the same time prevent the emergence of resistance
In fact, he adds, "the tumors treated with this triple combination were reduced and remained small, while those treated with the inhibitor G12C KRAS only tended to be reduced at first, but then began to grow again after two weeks. Our results suggest that it would be worthwhile to test this combination in human trials in the next few years, in order to prevent or at least delay the drug resistance.tumors treated with this triple combination were reduced and remained small, while those treated with the inhibitor G12C KRAS only tended to be reduced at the beginning
The other compounds in the combination block pathways mTOR and IGF1R, which have been tested previously in patients with cancer. There are already mTOR inhibitors to be approved, such as rapamycin, whereas inhibitors of IGF1R are still in the preclinical stage.
To develop this combination, the team used tumor cells derived from patient s with the mutation G12C KRAS. Edited these cells to block the activity of 16.019 genes different, and treated with compounds to which it is known that cancers with mutant KRAS are susceptible.
"we found that cell lines without the gene MTOR were significantly more vulnerable to inhibitors of KRAS and IGF1R," explains the first author, Molina-Arcas. "When we block the three pathways, the cancer cells mutants were unable to survive . This makes it a promising pathway for human trials in the next few years, although we are still in a research phase early. The promising results in mice and cells can tell us that it is worth a try, but it is impossible to predict how they will respond to the patients until you really try".These inhibitors are still in clinical trials, so it takes time for these drugs to reach reach of all patients
Explains Molina-Arcas that the work may have implications in the short or medium term for patients. For example, advances to ABC Health, "the pharmaceutical company Amgen is ending the first trials of the toxicity of inhibitors of G12C KRAS and already is discussing the possibility to start clinical trials with combinations. We propose to use inhibitors of mTOR and IGF1R. The mTOR inhibitors are already used in the treatment of several types of cancer, and inhibitors of IGF1R have been used in several clinical trials". In addition, he adds, the fact that the toxicity of the two inhibitors together has already been tested in clinical trials, with positive results, " deadline is shortened to reach patients ".
however, adds the researcher, "although there is great optimism in the scientific community on the use of inhibitors of G12C KRAS for the treatment of lung cancer, these inhibitors are still in clinical trials, so it takes time for these drugs to reach reach of all patients."Updated Date: 18 September 2019, 23:01