Researchers from the ICB (Institute of Biomedical Sciences) and the Faculty of Medicine at USP (University of São Paulo) have identified a possible new treatment for acute leukemia, types of cancer whose mortality in adults can reach more than 50%. With the synthetic molecule called THZ-P1-2, recently launched by the pharmaceutical industry, it was possible to eliminate more than 80% of tumors in trials ex vivo that is, made with cells taken from patients.
Acute leukemias are divided into two categories: AML (acute myeloid leukemia) and ALL (acute lymphoblastic leukemia). Most cases of ALL occur in children and do not usually lead to death, as there are many therapies already consolidated for these cases. AML, on the other hand, is more common in adults and the lack of therapeutic options for this age group helps to explain the high mortality rate.
“ Both are very aggressive. Patients who do not receive any treatment can progress to death within a few months. ”, said João Agostinho Machado-Neto, professor of the Department of Pharmacology, to ICB-USP.
Published in Blood Cancer Journal.
The work is linked to 2 projects funded by FAPESP and was coordinated by Machado-Neto at the Cancer Biology and Antineoplastics Laboratory of the ICB, in partnership with Eduardo Magalhães Rego, leader of the oncology and clinical hematology division of HC-FM-USP.
This is the 1st study to describe in detail the mechanism of action of this PIP4K2 protein inhibitor molecule in the treatment of cancer. The results are based on two hypotheses previously developed in the ICB laboratory.
“ The conditions of patients with AML who have higher levels of PIP4K2s evolve more quickly and are more likely to lead to death; already patients with polymorphisms [ variantes genéticas e hereditárias] in the PIP4K2A gene are more likely to develop ALL ”, told ICB-USP Keli Lima, doctoral student in medical sciences at FM-USP, 1st author of the study and FAPESP scholarship holder.
clinical studies
According to Machado-Neto, current therapies are restricted to bone marrow transplants and chemotherapy. However, many patients, particularly those over the age of 60, are not eligible for transplants.
In these cases, they are submitted to chemotherapy, but always in low doses, due to the toxicity of the treatment. These people can then receive venetoclax – a drug whose effectiveness is significant only for a portion of those affected.
“ In addition to already achieving high efficacy alone, the THZ-P1-2 molecule has also shown itself to be able to improve the response of leukemic cells to venetoclax and other drugs that are currently not effective enough to be used in the treatment, and may act together with them at a cocktail party ”, explained the professor.
The compound also obtained good results in a study with animal models conducted by a group from the Faculty of Medicine at Cornell University in association with Petra Pharma, both from the United States. In that work, the researchers identified that the molecule led to a rapid regression of the tumors and did not present toxicity. That’s the accreditation for clinical trials.
“ If these human studies started today, we could already know in two to four years if the drug is safe and effective ”, said the ICB professor.
THZ-P1-2 is under patent by a pharmaceutical company, so it is up to that company to conduct the studies. The ICB researchers now intend to analyze other PIP4K2s protein inhibitors.
“ After THZ-P1-2 was released, other companies developed similar molecules. Our job now is to test them to see which one gets the best results. ”, highlighted Machado-Neto. “ The most difficult part, which was to identify the mechanism of action of the inhibitors at the cellular and molecular level, we have already done ”, evaluated Lima.
With information from FAPESP Agency.