Joint Call (JTC 2017)

JTC 2017 focuses on: “Translational research on rare cancers”.The challenges related to research and treatment in rare cancers, are intimately tightened to the low incidence of any single clinical-pathological entity currently listed among these cancers.

On this basis, a network-based approach within the operating framework provided by TRANSCAN-2 could contribute to address compelling research questions in the area of interest.

Indeed, the development and consolidation of consortia based on international collaborations will allow to efficiently integrate resources spanning the entire continuum from diagnostics to therapeutics and maximize the efforts for collecting clinically annotated biological samples.

Such consortia will serve as a guide to pool scientific expertise, share novel insights and eventually train young investigators.

In this view, the proposals of the present call will have to cover a minimum of one of the specific aims reported below, and within the aim/s of choice, the applicants will have to address at least one of the topics listed as bullet points.

Proposals addressing one single aim and one single bullet point within the chosen aim will be allowed.

Aim 1: Design and conduct of translational research studies exploiting/combining resources from current clinical trials, bio-repositories and epidemiology-type resources.Translational cancer research on aetiology, pathogenesis and prognosis of rare cancers is tightly linked to the integrated use and facilitated access to biospecimens from patients.

Translational research goals in rare cancers may thus be achieved throughout studies of cohorts of patients with available biospecimens adequately stored in biorepositories linked to cancer registry data.Translational studies based on the analysis of data and/or of clinically annotated specimens from previously conducted/ongoing trials with adequate follow up.Conduct of studies for cancer risk assessment in rare cancers leveraging upon access to institutional and/or national cancer registries.Identification and characterization of the etiopathogenetic determinants involved in rare cancers aiming at increasing our knowledge of the underlying pathways to be targeted by means of existing or experimental therapies.

Aim 2: Development and exploitation of translational research platforms (e.g., patient derived xenograft models/organoids/tissue collections) to study drug responses/resistance and toxicity, and perform drug screens or repurpose approved anticancer drugs.- Tissue collection, and genetic and epigenetic characterization of patient-derived rare tumors xenografts (PDXs).

PDX could be used to identify determinants of heterogeneity in patient response to therapy, and thus inform patient-oriented therapeutic decisions.

PDX could be used to screen for candidate pathways and/or therapeutics.- Three-dimensional cultures (or 'organoids') obtained from patients’ rare tumors which closely replicate key properties of the original cancers.

Organoid cultures could be amenable to the detection of genetic and/or epigenetic changes associated with drug sensitivity and may thus lead the way to targeted approaches that could improve clinical outcomes in cancer patients.- Other translational research platforms that give insights into the drug responses/resistance and toxicity of drugs, and help perform drug screening for the treatment of rare diseases (e.g., induced pluripotent cell clones established from patient tumors and normal cells and induced to differentiate in vitro).

AIM 3: Implementation of precision biomarkers for better stratification of the clinical cohorts.- Validation and implementation of rare cancers associated biomarkers as molecular predictors of therapeutic response, treatment resistance and disease outcome.- Use of innovative, high throughput technologies designed to facilitate the comprehensive ‘omic assessment of genomes, transcriptomes, proteomes, metabolomes, etc. of patients affected by rare cancers.- Design and conduct of phase I and/or phase II clinical studies aiming at the validation and implementation of precision biomarkers (including approaches based on liquid biopsies to enable non-invasive assessment of tumour heterogeneity and to monitor tumour dynamics) in patients diagnosed with rare cancers.