Abstract
Cancer is a major public health problem worldwide and ranks among the leading causes of death. Identifying new agents for the diagnosis and treatment of patients with cancer is highly desirable. For many centuries, metals have been used empirically to treat various diseases. Nowadays, metals and their compounds - stable or radioactive - are rationally applied in both the diagnosis and treatment of neoplasms. A new type of cancer approach has gained worldwide prominence, the theranostic approach, a deriving term from "therapy" and "diagnosis". The overall theranostics concept involves identifying an active molecule related to a treatable target and subsequently radiolabeling the molecule for diagnosis (gamma or positron emitters) and therapeutic purposes (alpha or beta emitters). By reuniting researchers from a wide range of fields of expertise including such as Clinical Oncology, Onco-Hematology, Chemistry, Nuclear Medicine, Pharmacy, Statistics, Biology, and Physics, the effort aims to produce a Cancer Theranostics Innovation Center (CancerThera). CancerThera's goal is to develop an internationally competitive research center with qualified human resources for the creation and manipulation of pharmaceuticals and radiopharmaceuticals ((radio)pharmaceuticals) for the diagnosis and treatment of cancer in a theranostics approach. CancerThera will be divided into two interconnected teams - Basic Research and Clinical Research - which will develop converging projects. CancerThera Basic Research: Bioactive molecules will serve to synthesize new Metallo(radio)pharmaceuticals with potential action in diagnosis and blockage of tumor cell replications. Compounds and chelators will be conjugated with various tumor microenvironment-related peptides. The compounds will be radiolabeled with the pair gallium-68 and lutetium-177, which, respectively, allow the diagnosis and treatment of neoplasms, in addition to other radioisotopes. The biodistribution and/or antitumor action of the compounds will be evaluated in various preclinical studies. Investigations will include gamma counter analysis, micro-PET/SPECT/CT imaging, antiproliferative activity and cell death assays in tumor cell lines, and conventional evaluation. Further, inflammation/gene expression assays of toxicity and efficacy will be performed in animal tumor models. CancerThera Clinical Research: Possible new uses for already known molecules will be studied. The existing radiopharmacy at the host institution will be further set up and developed by the International Atomic Energy Agency project in force. The current radiopharmacy infrastructure will label various diagnostic oncology-based radioisotopes for possible cancer treatments. Investigations will be conducted on various cancer types (such as multiple myeloma, indolent lymphomas, colorectal and gastric cancers, glioblastoma multiforme, head, and neck cutaneous squamous cell carcinoma, Ph1-negative chronic myeloproliferative diseases, etc.). Genetic analysis of the radioactive-avid lesions will be performed. Continuous interaction between the CancerThera Basic and Clinical Research teams will take place in an unprecedented model in the country in this area. Thus, the radiopharmaceuticals successfully produced in Basic Research will be used in phase 1 and, eventually, phase 2 clinical studies. Likewise, new applications of known drugs will have their radiolabeling monitored by the Basic Research investigators. To ensure appropriation of the results of CancerThera by the society, different players from several institutions will be interconnected including investigators, scholars, research organizations, national and international funding agencies, micro-enterprises and large business corporations, governments (state and municipal), press, and ultimately the Brazilian society. (AU)
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