Towards an Easy-to-use Adrenal Cancer/Tumor Identity Card

Overview

Malignant pheochromocytoma/paraganglioma (MPP) and adrenocortical carcinoma (ACC) are two rare cancer entities with a very unfavorable prognosis. The knowledge on these rare cancers improved thanks to the French COMETE network originally based on two clinical centers (HEGP and Cochin) well organized for clinical and biological samples collection. Over the last 10 years, the COMETE key partners deciphered molecular mechanisms of tumorigenesis and oncogenesis of these tumors and identified molecular signatures discriminating between benign and malignant cancers by integrated genomic approaches. This strategy was highly successful in delivering new diagnostic applications of genomics technologies that now appear as potentially suitable for rapid implementation in routine clinical care. The main objective of COMETE-TACTIC is to provide an easy-to-use "identity card" of the adrenal tumors that will allow a personalized "à la carte" management of the patient and, when indicated, to the indication of the most accurate molecular targeted therapy. We hypothesize that the improvement of MPP and ACC diagnosis and of the therapeutic options proposed to affected patients will require, 1. the transfer to routine practice and the prospective validation of the novel diagnostic and predictive biomarkers issued from recent discoveries (genetics, genomics, histological biomarkers); 2. the implementation of the translational research projects based on the COMETE collection to identify circulating diagnostic, prognostic and therapeutic genetic and metabolic biomarkers that could be used as non-invasive "liquid biopsies".

Malignant pheochromocytoma/paraganglioma (MPP) and adrenocortical carcinoma (ACC) are two rare cancer entities with a very unfavorable prognosis. The knowledge on these rare cancers improved thanks to the French COMETE ('COrtex, MEdulla Tumors Endocrines') network originally based on two clinical centers (HEGP and Cochin) well organized for clinical and biological samples collection. Over the last 10 years, the COMETE key partners deciphered molecular mechanisms of tumorigenesis and oncogenesis of these tumors and identified molecular signatures discriminating between benign and malignant cancers by integrated genomic approaches. COMETE has published more than 200 papers and performed seminal work on the pathophysiology and the genetics of MPP and ACC published in high-impact journals. This strategy was highly successful in delivering new diagnostic applications of genomics technologies that now appear as potentially suitable for rapid implementation in routine clinical care. The main objective of COMETE-TACTIC program is to design and validate an easy-to-use "identity card" classifying MPP and ACC in clinical routine, using molecular genomic and metabolomic tools combined with histopathological-based tests, to provide a real help for early diagnosis, prognostic as well as a personalized "à la carte" management and treatment to patients with malignant adrenal tumors. Seven teams, with an expertise in genomics of adrenal tumors, or in metabolomics approaches, or in clinical research and statistical analyses collaborate in COMETE-TACTIC. COMETE-TACTIC will be based on an already constituted large cohort of 850 patients that will be enlarged by the prospective enrolment of new cases and biological samples (300 to 450 new cases during the 3 years of the project) via 21 French expert and/or competence centers of COMETE-Cancer Reference center. Previous COMETE basic studies provided important new insight for the understanding of molecular mechanisms responsible for MPP or ACC. With the transfer of "Omics"-based tests from research laboratories to clinical practice, COMETE-TACTIC is the next step toward a personalized medicine for patients with MPP and ACC. COMETE-TACTIC should speed the transfer in routine clinical care of new biomarkers based on cutting-edge technologies combining advanced pathology assessment and targeted genomics and metabolomics to diagnose malignancy and predict outcome, and thereby facilitating a more accurate, rapid and reliable diagnostic work-up for patients. This personalized management will help to avoid delayed diagnosis and to direct clinical decisions resulting in a better health outcome for the patients. COMETE-TACTIC will offer the access to a precise molecular classification of MPP and ACC that should guide targeted therapies. Finally, COMETE-TACTIC will investigate for the first time the impact of circulating biomarkers for the diagnosis and prognostic of adrenal cancers that will be further tested as biomarkers of response to targeted therapies.