Researchers from the ICB-USP (Institute of Biomedical Sciences of the University of São Paulo) are testing a possible new drug for lung cancer: the compound NT157.
in experiments in vitro the synthetic molecule proved to be capable of acting on several disease targets inhibiting the proliferation of tumor cells and potentially preventing resistance to radiotherapy, chemotherapy and other drug interventions.
Published in article on Scientific Reports, the study was conducted by the Laboratory of Cancer Biology and Antineoplastics of the Department of Pharmacology at ICB-USP, in partnership with Harvard University, in the United States. The group was supported by FAPESP.
Understand. NT157 is a drug candidate that is being tested in laboratories with a focus on lung cancer. In previous studies, in vitro and in animal models, it has already shown promise with breast, prostate and colorectal cancers, among others.
“It is the first time that NT157 has been studied for lung cancer. With this study, we obtained proof that it is an effective drug, as it interrupts IGF-1, a cellular pathway that promotes the growth of tumors, and inhibits the expression of genes in the AXL pathway, which promotes the development of drug resistance, an inhibition that we detail firsthand”, explains Professor João Agostinho Machado-Neto, research coordinator, to the ICB-USP Press Office.
“Due to the fact that the compound acts on multiple targets, that is, on more than one cell and more than one receptor, it is more difficult for cancer cells to develop resistance”, he adds.
How the study was done. The laboratory experiments were all developed at the ICB. Harvard researchers helped with suggestions for new experiments and guided discussion of results and design of further studies. Among the main contributions of the American group is the conception of the idea of combining NT157 with gefitinib, a drug already used against lung cancer.
“We point out that the effect of NT157 is potentiated when it is applied together with gefitinib, opening up possibilities for new therapeutic combinations”, highlights Lívia Bassani Lins de Miranda, doctoral student in the laboratory, FAPESP scholarship holder and co-author of the work.
no metastasis
The findings were observed in two cells in 2D and 3D models, created to simulate a lung with greater fidelity.
“In both models, we observed that with NT157 the tumor does not go beyond this structure, thus preventing the disease from spreading to other organs and causing metastasis. This could increase the patient’s quality of life and survival”, explains the USP professor.
Because it is a molecule that has not yet been tested, science still does not know exactly how it works in the body.
However, ICB research has helped to describe the mechanism by which it acts, the so-called Jun kinase simulation, also known as JNK.
“In 3D cells, we saw that the drug is capable of activating Jun kinase, an enzyme that regulates the self-destruction process of cells, which can accelerate the death of tumor cells”, points out Miranda.
And now? To assess whether NT157 is effective and safe in humans, further studies are needed.
Thus, the researchers will now validate the results in animal models. At the same time, ways of applying the medicine directly to the lungs, via inhalation, are being studied to avoid possible adverse effects with the circulation of the medicine through other organs.
NT157 exerts antineoplastic activity by targeting JNK and AXL signaling in lung cancer cells can be read at: www.nature.com/articles/s41598-022-21419-6.