A multicenter collaboration has identified a potential new treatment for an aggressive sarcoma arising in the nerves. The findings have been Published in the journey Clinical Cancer Research,

It may sound strange, but tumors may arise in the nerves. This is the case of the malignant peripheral nerve sheath tumor (mpnst), an aggressive sarcoma with a high tendency to metastasize.

Sarcomas are a group of tumors originating from cells of the connective tissue, like bone, cartilage, muscle, fat or the nereve sheath, where mpnsts arise. About 50% of mpnsts appear in the general population, whose 50% development in the context of the genetic disease neurofibromatosis type 1 (nf1), where individuals heaved Or, affecting both children And adults.

A Valuable Resource: A Pre-Clinical Platform for Precision Medicine

Currently, there is lacked of effective therapy for mpnsts beyond timely surgery, since conventional radio or chemotherapy do not show very good responses.

This Lack of Therapeutic Options Prompted, Almost 15 years ago, The teams of Dr. Conxi Lázaro (Hereditary Cancer at Idibell) and Dr. Eduard Serra (Hereditary Cancer at IGTP), Togeether with the Expertise of Dr. Alberto Villanueva and the Collaboration of Different Clinicians Like Dr. Ignacio Blanco, to Develop a Robust Preclinical Platform Consisting of PATINT-DERIVED XENOGRAFTS (PDX) of Human mpnsts implanted in the nerves of immunodeficient and the establasty L lines.

“It has been a patient and long collaborative work of many years that is now at its maturity. Thank many people involved, particularly Dr. Valuable and Constant support, even in Difential Times, Allowed The Development of this Platform, “Mentioned Dr. Lázaro, one of the Senior Author of the work.

ALL MODELS and Primary Tumors have ben genomically characterized and compared, enabling their use in precision medicine strategies, where drugs are tailored to treat tumors base h case. Over time, this resource has grown significantly, now comprising many different mpnst models, and serving as a foundation for drug screening to predict treatment responses.

“The Most Common Type of Mpnsts Initiate by Losing The Function of Three Important Ganes, Called Tumor Suppressor Ganes: NF1, CDKN2A and PrC2 (EITHER Suz12 Oor Eed). Geting the pathways affected by these mutations alredy exist. Building on top of the work of other research teams – 40 and research is like being a ‘Casteller’ – White Initiated The Project to Combine these these drugs and evaluate their potent for clinical Application, “Stated Dr Serra, the other Senior Author of the work.

From drug screening to the clinics: research with impact

In a first step, researchers took advantage of a fruitful collaboration with Dr. Marc ferrr, at the National Center for Advanceing Translational Sciences (NCATS) at NIH (US), and Used Robotics to Screen Hundreds of Combinations of Different inhiTors of Different Ki to target the loss of cdkn2a And beti to target the loss of prc2 function.

The best combinations were selected, validated in vitro using an extended panel of mpnst cell lines, and finally tested in Vivo Using the PDX PRECLINICAL PLATFORM, which represents, both nf1-pot and sporated. Researchers Found Good Responses when Using Selected Combinations of Two Different Inhibitor Classes, Meki-Beti, but the Best Responses WHEND WHEN Using the Combined Action of the Thi Dki.

“Initially, We We We WE WERE Pearing completely with the triple meki-beti- CDKI Combination. After all the hard work, see the potential applications was ankredibly rewarding moment, “Explained Sara Ortega, The Firist Author of the Wort H.D. Thesis that will be defended this year.

At this point, it was close collaboration with clinicians, Especially Dr. Héctor salvador from the pediatric cancer center at hospital sant joan de déu, that made poses

Initially, the Findings supported the compassionate use of the meki-beti combination in pediatric patients with mpnst. Dr. Salvador, Togeether with Dr. Claudia Valverde, from Vall D’Hebron Hospital, Facilized Access to New Inhibitors, which are currently undergoing testing in clinical environments.

Additionally, Dr. Salvador and Alicia Castañeda have started to administer the meki-beti combination as compassionate use for children affected by mpnsts. For the meki-beti-cdki combination, further preclinical studies are needed to optimize administration regimens and minimize toxic effects. However, these promising results, combined with a clinical trial current underway in the US LED by Other Clinical Groups, AIM to Provide the Necessary Evidence to Enable his broader Clinical Application in the neck

“There is still a lot to do – Further preclinical data, optimized treatment regimens, reduced toxicity – but the first steps for precision Medicine in the Future ARALREADY In Place,” Concluded the TEM.

Provided by Germans I Pujol Research Institute