researchers of the Hospital del Mar Institute of Medical Research (IMIM) and the Biomedical Research Institute (IRB) of Barcelona have discovered that adding a peptide, a molecule made up of several amino acids, to oxaliplatin, the standard chemotherapy to treat the colon and rectal cancer, avoid side effects of this treatment.
The new drug, published by the magazine ‘Journal of Medicinal Chemistry‘, also reduces the possibility of developing resistance to chemotherapyaccording to the researchers, who have explained that this new approach prevents the healthy cells that surround the tumor from hoard platinum and that genes linked to poor response to treatment and tumor progression are activated.
The work, which has also had the participation of doctors from the Hospital del Mar Pathology and Medical Oncology services and researchers from the University of Oviedo and the CIBER of Cancer (CIBERONC), is a further step towards personalization of the therapeutic approach to cancer.
This same group of researchers had already verified, in a work published in ‘Nature Communications’how this type of chemotherapy accumulates in the healthy cells that surround the tumor, the fibroblasts, and this causes a series of genes linked to creating resistance to treatment and helping tumor cells that survive chemotherapy to be activated.
To avoid this, the researchers have proposed adding a specific peptide (cell-penetrating peptide, in English) to oxaliplatin.
“Converting a systemic treatment, which affects healthy organs and the tumor microenvironment, by adding this peptide, allows us to transform it into something more specific, a targeted therapy, thus approaching personalized medicine”, highlighted the IMIM-Hospital del Mar Alexandre Calon.
200 patients analyzed
This finding is based on the analysis of tumors from about 200 patients with colon and rectal cancer and also from tumor samples from mice and from patients treated ex vivo to verify that adding a peptide to oxaliplatin decreased the adverse effects of this chemotherapy in normal tumor cells, therefore it could reduce resistance to this treatment.
The results indicate that the platinum accumulation in the microenvironment of tumors of mice treated with this new approach drops drastically and is up to 3.5 times less.
“We have seen that the chemotherapy load is reduced in fibroblasts treated with the new compound compared to those treated with oxaliplatin, which reduces the possibility of inducing resistance to treatment in tumor cells,” Calon has indicated.
“Hence the importance of taking into account that cancer is not only tumor cells, but also a microenvironment made up of blood vessels, fibroblasts and cells of the immune system, which are there to structure the tumor,” he added.
The researchers have also identified that the new drug not only accumulated less around the tumor in the mice, but also in the organs that are normally most affected by chemotherapy, such as the colon itself.kidneys and liver.
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Jenniffer Linares, researcher from the same group, has summarized that “classical treatment has a host of side effects in the patient, which we think could be reduced with the new drug, as less platinum accumulates in healthy tissues.”
“This study is an essential first step for a future development in the clinic of treatments that allow fewer side effects and greater efficacy in patients with colon and rectal cancer, taking into account that the normal cells that are part of the tumors play a role key in the effectiveness of the treatments”, concluded the head of the gastrointestinal tumors section of the Hospital del Mar, Clara Montagut