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Experimental treatment improves skin cancer survival by 25%
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Experimental treatment improves skin cancer survival by 25%.
An experimental treatment with a protein-derived molecule reduced tumor growth and metastasis and improved survival by 25 percent.
A recent study published in Scientific Reports shows that the polypeptide Rb4, developed by Brazilian scientists, is effective in fighting cancer growth in animal models, particularly malignant melanoma.
The peptide also has the potential to treat drug-resistant tumors.
In preclinical in vitro and in vivo experiments, Rb4 caused necrosis of mouse melanoma cells and reduced the viability of human cancer cells.
The tumor cells in the experiments lost the integrity of their plasma membranes, expanded mitochondria (energy-producing organelles), and even in the absence of chromatin condensation, a morphological hallmark of apoptosis.
The researchers acknowledge that they still don’t fully understand what causes this necrosis.
The peptide also reduced lung metastases and reduced subcutaneous melanoma development in mice.
The findings suggest that Rb4 acts directly on tumors to induce the expression of two damage-associated molecular patterns (DAMPs), leading to apoptosis in immune melanoma cells.
Before and after peptide Rb4 acts on tumor cells. Source: Fabrício Castro Machado
“In the search for new molecules, Rb4 derived from proteolipoprotein 2 [PLP2] has shown a preference for causing necrosis, a specific type of cell death, especially in melanoma, but this necrosis is How it occurs and develops is unclear. This article discusses some aspects of the morphological composition of the peptide, and the final effects of contact with it,” co-author Fabrício Castro Machado told Agência FAPESP.
Machado was a member of the Experimental Cancer Group of the Department of Microbiology, Immunology and Parasitology of the Federal University of São Paulo (UNIFESP), Brazil, and is currently a researcher at Recepta Biopharma (ReceptaBio), a Brazilian biotech company developing cancer drugs (hence the peptide name “Rb” in ).
With the support of FAPESP, a group led by Luiz Rodolpho Travassos, professor emeritus at UNIFESP, began the research.
The authors of this article pay tribute to Travassos, who passed away in 2020, who published more than 230 articles in leading scientific journals, many of them on peptides and peptidases (enzymes that break down proteins into peptides and ultimately into single amino acids) ) in infectious diseases and cancer research. Because of this interest, in 2008 he contacted ReceptaBio, whose CEO is José Fernando Perez, former scientific director of FAPESP (1993-2005).
“Professor Travassos has sequenced several bioactive peptides, small molecules based on antibodies developed by ReceptaBio. Rb4 was also discovered during this search for new molecules, although it was not derived from antibodies.” R&D analysis by ReceptaBio “We also have an Rb9, which is at a more advanced research stage with several papers and patents, but is still in the preclinical stage,” said Alice Santana Morais, a teacher and the article’s corresponding author.
In 2016, scientists described the structure of Rb9 and its mechanism of action as a suppressor of melanoma cells.
A recent article published in 2020 showed that Rb9, as an immunomodulator, could be used to control tumor progression.
“Whether it’s in academia or a company like ReceptaBio, we need to do research together,” Morais said. “We’re looking for partners to facilitate the drug development process, which is long and painstaking and requires discussions, details and exchange of experience.”
Novel cancer treatments developed in recent years include peptide-based chemotherapy.
Peptides have received increasing attention not only because of their ability to bind to the membranes of tumor cells, but also because of their low molecular weight, good cellular tissue permeability, and low toxicity to normal tissues.
They can be used as carriers for cellular reagents, ligands, vaccines and cytotoxic drugs, for polypeptide therapy alone or as materials for polypeptide conjugation.
In a study on Rb4’s antitumor effects, the team found that the peptide interfered with the morphology, replication and association of B16F10-Nex2 melanoma cells grown in the laboratory.
Compared to controls, cells treated with Rb4 did not replicate and form colonies, losing their natural morphology after up to 24 hours of culture.
In addition, Rb4 also reduced the number of lung metastatic nodules in a synthetic melanoma model involving tumor tissue from mice with the same genetic makeup.
The results were detected after melanoma cells were injected intravenously into mice.
Five intraperitoneal injections of the peptide (300 micrograms per animal) on alternate days delayed tumor growth by 40 days. Mice treated with Rb4 had significantly higher survival rates than controls, with population survival increased by more than 25% for up to 10 days.
Melanoma originates in cells that produce melanin, the pigment that gives skin its color. It can appear in various parts of the body.
Although skin cancer is the most common form of cancer in Brazil, accounting for 30% of all cases, melanoma accounts for only 3% of malignant tumors.
However, it is the most life-threatening because it is likely to spread to other organs (metastasis).
According to estimates by the National Cancer Institute (INCA), there are approximately 8,400 melanoma cases in Brazil each year. The disease killed 1,978 people in 2019.
Experimental treatment improves skin cancer survival by 25%
(source:internet, reference only)