Sant Joan de Déu researchers develop a method to predict the efficacy of a nanodrug in Ewing's sarcoma
The discovery will allow better selection of patients with this childhood cancer in whom medicine has a real chance of success.
Researchers at SJD Pediatric Cancer Center Barcelona at SJD Barcelona Children’s Hospital, have developed a method that predicts the anticancer efficacy of nab-paclitaxel, a well-known nanomedicine, in mouse models, for treatment of Ewing sarcoma, a severe cancer affecting the bones and soft tissue of children and adolescents.
Researchers have discovered that only Ewing sarcomas devoid of a protein named Bcl-2 in their cancer cells respond well to this medicine. The discovery will facilitate the selection of the patients for which this treatment would have real chances to succeed.
The journal Biochemical Pharmacology has recently published the research.
Nab-paclitaxel is made of albumin particles bound to paclitaxel. It was developed by Celgene, a Bristol Myers Squibb Company. Nab-paclitaxel is approved for use as first-line treatment in adult patients with metastatic pancreatic adenocarcinoma, breast cancer and non-small cell lung cancer.
In children, this treatment is currently undergoing experimental phases in the frame of clinical trials. SJD Pediatric Cancer Center researchers have discovered that nab-paclitaxel was not efficacious in Ewing sarcomas whose tumour cells contain protein Bcl-2.
In addition to Ewing sarcoma, researchers studied other paediatric tumours, such as rhabdomyosarcoma and Wilms tumour. In these tumours, however, they did not find a clear relationship between the presence or absence of Bcl-2 and the efficacy of nab-paclitaxel.
The director of the study, Dr Angel Montero Carcaboso, explains that the research was conducted in 28 tumours obtained from paediatric patients and engrafted in mice, to identify a common ground in all of them that would identify the tumours responding better to the treatment. "Most of these tumours, 15, were Ewing sarcomas, among which three completely disappeared after treatment. We did not find Bcl-2 in these three tumours", he says.
“For eight years -he adds- we engrafted tumour fragments from new patients in mice and performed studies until we obtained a number high enough to provide statistical power to identify a marker of response to treatment, a biomarker". The study suggests that one in every five patients with tumours resistant to first and second line treatments could obtain a benefit from this nab-paclitaxel, after going through an easy and fast test to detect Bcl-2 in their cancer cells.
A new treatment combination becomes possible
The study also proposes a method to increase the nab-paclitaxel efficacy in patients whose tumours are Bcl-2-positive, because there are treatments available to annul the action of this protein. "We observed that the combined therapy with a Bcl-2 inhibitor reverted resistance to nab-paclitaxel in some of the tumours”, points out Guillem Pascual-Pasto, first author of the study.
The scientific activity of SJD Pediatric Cancer Center is part of one of the research programs of the Institut de Recerca Sant Joan de Déu (IRSJD), recognized by the Government of Catalonia as a research center of excellence. Dr. Angel Carcaboso currently leads the Pediatric Cancer Treatment research group within the IRSJD.
Bibliographical citation: G. Pascual-Pasto, C. Resa-Pares, H. Castillo-Ecija, R. Aschero, M. Baulenas-Farres, M. Vila-Ubach, V. Burgueño, L. Balaguer-Lluna, M. Cuadrado-Vilanova, N.G. Olaciregui, N. Martinez-Velasco, S. Perez-Jaume, E. de Alava, O.M. Tirado, C. Lavarino, J. Mora, A.M. Carcaboso, Low Bcl-2 is a robust biomarker of sensitivity to nab-paclitaxel in Ewing sarcoma, Biochemical Pharmacology (2023) 115408.