Molecular characterization of soft-tissue sarcomas: integration of translational preclinical models and functional study of genetic alterations with clinical relevance

• Grant number: 18/25541-8
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2019
• End date: July 31, 2022
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Tiago Góss dos Santos
• Grantee: Tiago Góss dos Santos
• Host Institution: A C Camargo Cancer Center. Fundação Antonio Prudente (FAP). São Paulo , SP, Brazil
• Associated researchers: Andrea Bertotti ; Celso Abdon Lopes de Mello ; Giovana Tardin Torrezan ; Glaucia Noeli Maroso Hajj ; Israel Tojal da Silva ; Vilma Regina Martins

Abstract

Soft tissue sarcomas (STS) are rare neoplasms with different morphological patterns of mesenchymal cells that can evolve with high rates of morbidity and mortality. High-grade tumors larger than 10 cm and deep have a worse prognosis due their high metastatic capacity (mainly to the lungs), with median survival not exceeding 15%. The low efficacy in the treatment of these tumors is in part related to the little existing knowledge about the biological characteristics that govern these tumors. Therefore, the search for molecules capable of modulating the biology of these tumor types can bring substantial improvements to the treatment of the disease. For the development of new therapies, it is necessary to study the function of the molecular alterations peculiar to this group of tumors. In this sense, consortia such as The Cancer Genome Atlas (TCGA) make an immense contribution to providing the scientific community with the complete landscape of molecular alterations in thousands of patients with tumors, including sarcomas. However, for such initiatives to make sense, these studies need to be complemented with research into the role of specific tumor changes in order to identify potential therapeutic targets that could benefit patients. Therefore, the objective of this project is to establish an integrated, convergent and translational platform for STS. The structuring will be based on the exploration of TCGA data, preclinical experimental models (PDX, patient-derived xenografts e PDO, patient-derived organoids) and samples from A.C. Camargo Cancer Center patients. The identification of clinically relevant molecular alterations will be explored in cell lines, PDX and PDO. The identified targets that present potential for clinical application will be evaluated for their prognostic, predictive and therapeutic power. Therefore, the Lgr5 receptor (stem cells marker in intestinal crypts) has become a target because its increased expression in 15% of TCGA cases, highlighting its application as a potencial targeted therapy in STS. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DE CAMPOS, NAJLA SANTOS PACHECO; DE OLIVEIRA BESERRA, ADRIANO; PEREIRA, PEDRO HENRIQUE BARBOSA; CHAVES, ALEXANDRE SILVA; FONSECA, FERNANDO LUIZ AFFONSO; DA SILVA MEDINA, TIAGO; DOS SANTOS, TIAGO GOSS; WANG, YUFEI; MARASCO, WAYNE ANTHONY; SUAREZ, ELOAH RABELLO. Immune Checkpoint Blockade via PD-L1 Potentiates More CD28-Based than 4-1BB-Based Anti-Carbonic Anhydrase IX Chimeric Antigen Receptor T Cells. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 23, n. 10, p. 17-pg., 2022-05-01. (14/50943-1, 18/14034-8, 18/17656-0, 18/25541-8)

MELLO, CELSO ABDON; BATISTA CAMPOS, FERNANDO AUGUSTO; SANTOS, TIAGO GOSS; GOBO SILVA, MARIA LETICIA; TORREZAN, GIOVANA TARDIN; COSTA, FELIPE D'ALMEIDA; FORMIGA, MARIA NIRVANA; NICOLAU, ULISSES; NASCIMENTO, ANTONIO GERALDO; SILVA, CASSIA; et al. Desmoplastic Small Round Cell Tumor: A Review of Main Molecular Abnormalities and Emerging Therapy. CANCERS, v. 13, n. 3, FEB 2021. (14/50943-1, 18/06269-5, 18/25541-8)