DRUG REPURPOSING IN OSTEOSARCOMA: BETWEEN OPPORTUNITIES AND UNMET NEEDS

GARONA J; SOLERNÓ LM; SOBOL NT; LLAVONA, C; GOTTARDO MF; VÁSQUEZ, LILIANA; CHANTADA G; ALONSO DF

Mar del Plata

Congreso; REUNIÓN CONJUNTA SAIC SAI&FAIC SAFIS 2022; 2022

Sociedad Argentina de Investigación Clínica

Osteosarcoma (OSA) is the most prevalent primary bone cancer, mainly affecting children and adolescents, and represents a great clinical challenge given its limited re-sponse to therapy and early metastatic progression. Theprognosis for these patients is even more dismal in low-and middle-income countries, probably linked to late di-agnosis and inadequate access to therapeutic resources.In this context, the research and implementation of newcost-effective therapeutic tools is mandatory to improvethe prognosis of patients with OSA. Since signaling as-sociated with vasopressin receptors (AVPRs) and β-ad-renergic receptors (ADRBs) regulates many cellular andmicroenvironmental processes linked to cancer initiationand progression, multiple efforts have been made by ourgroup and others to reposition the hemostatic agent des-mopressin (dDAVP) and the β-blocker propranolol (PPN)in oncology. Using different experimental models of OSA,as well as clinical samples, our group has begun to studyits antineoplastic activity at the preclinical level, explor-ing associated mechanisms of action and the expressionof the respective therapeutic targets in tumor tissue.Evaluated compounds displayed a potent direct and tar-get-mediated cytostatic action, modulating key phenom-ena in malignant progression, such as apoptosis, cell cy-cle, 3D growth, cytoskeleton dynamics and chemotaxis,among others. Using dosage schemes with translationalrelevance, these drugs inhibited the growth of humanOSA xenografts, modulating their aggressiveness anddifferent histological parameters associated with thera-peutic response, especially in combination with cytotoxicagents. As a result, the repositioned agents dDAVP andPPN could be postulated as coadjuvant agents for themanagement of OSA, in combination with chemotherapyor administered in the perioperative setting. Consideringthat developing countries concentrate 80% of all newcases of pediatric cancers worldwide, drug repurposingin oncopediatrics represents an extremely interestingparadigm that stands as an alternative to de novo devel-opment of antineoplastic agents. Interdisciplinary workand integration of Applied research in OSA with hospitalgroups, is key for deepening our studies and favoring thetranslation of results to the clinic.