The biotechnology company Iproteos, IBEC and the Vall d’Hebron Research Institute (VHIR) are set to develop an innovative treatment to slow down, stop and even reverse the growth of solid tumors, which represent more than 90% of cancer cases.
It’s a family of peptidomimetic drugs based on a totally new anti-tumor action mechanism, the result of several years of research by Pere Roca-Cusachs’ group at IBEC.
The Translational Research in Child and Adolescent Cancer group at VHIR will evaluate candidate drugs, developed with Iproteos’ IPROTech technology, in pediatric tumours in vitro and in vivo.
The project, which received €935,000 in MINECO’s 2017 Retos Colaboración call, will focus in its first phase on two of the most common solid tumors in children and adolescents, rhabdomyosarcoma and neuroblastoma, as well as in lung and colon cancer, which have the highest mortality rate in adults.
An innovative anti-tumour action mechanism
Researchers from IBEC’s Cellular and Molecular Mechanobiology group, led by Pere Roca-Cusachs, discovered that the binding of proteins talin and vinculin – triggered by mechanical forces exerted by cells in response to an increase in rigidity of the surrounding tissue – triggers the activation of an important oncogen called YAP, present in most solid tumors. The results of the research – published in Nature Cell Biology in 2016 – revealed that the inhibition of the interaction of both proteins prevents activation of YAP, and has the potential to slow down, stop or even reverse tumor growth.
“Instead of focusing on genetic mutations or biochemical factors, we intend to attack tumors based on their mechanical properties, which undergo major changes”, explains Pere. “This represents a completely new strategy in cancer therapy that could potentially be revolutionary, and be used in combination with other more conventional therapies”.
The biotechnology company Iproteos will address the design, synthesis and characterization of molecules that inhibit the interaction of talin and vinculin using its IPROTech platform, a state-of-the-art technology that combines computational (in silico) chemistry tools with biotechnology (in vitro) to accelerate the design of a new generation of peptide-based drugs.
“The new mechanism discovered by Pere’s group is of great relevance, given its prevalence in the majority of malignant solid tumors, the most frequent in cancer”, says Teresa Tarragó, co-founder and CEO of Iproteos. “This project has great potential, since it encompasses a broad market that calls for new innovative drugs that can help improve current survival rates. Our IPROTech platform will play a fundamental role, as it allows us to obtain drugs for complicated targets, such as protein-protein interactions.”
The Translational Research in Child and Adolescent Cancer group at VHIR, led by Dr. Josep Sánchez de Toledo and Dr. Soledad Gallego, will evaluate the anti-oncogenic effects of the drug candidates in pediatric tumors in vitro and in vivo, a study that will be led by Dr. Josep Roma. Obtaining results on bioavailability, pharmacokinetics and pharmacodynamics will be key to the development of the project, as well as being crucial for initiating the concept tests at the optimum dose.
“This project opens a new promising avenue for the development of new drugs based on highly innovative biological mechanisms for the fight against cancer”, says Dr. Roma. “Research to develop new drugs often focuses exclusively on adult tumors and ignores tumors in children, so that’s even more added value for the project. The solid infant tumors included in this study still show a clearer survival below the average for children’s cancers, and therefore, it is very necessary to study new ways of treatment in order to improve their survival rates”.
The year-long project, “Development of an innovative therapy for the treatment of solid tumors by means of the inhibition of the mecanotransduction”, has received a grant of € 935,000 euros from the Ministry of Science, Innovation and Universities through of the call Retos Colaboración 2017 of the ‘Programa Estatal de I+D+i Orientada a los Retos de la Sociedad’ (Exp. RTC-2017-6505-1).
From left to right: Pere Roca-Cusachs, Josep Roma, Teresa Tarragó