RÉSUMÉ
Extracellular vesicles (EVs) secreted by tumors are abundant in plasma, but their potential for interrogating the molecular features of tumors through multi-omic profiling remains widely unexplored. Genomic and transcriptomic profiling of circulating EV-DNA and EV-RNA isolated from in vitro and in vivo models of metastatic prostate cancer (mPC) reveal a high contribution of tumor material to EV-loaded DNA/RNA, validating the findings in two cohorts of longitudinal plasma samples collected from patients during androgen receptor signaling inhibitor (ARSI) or taxane-based therapy. EV-DNA genomic features recapitulate matched-patient biopsies and circulating tumor DNA (ctDNA) and associate with clinical progression. We develop a novel approach to enable transcriptomic profiling of EV-RNA (RExCuE). We report how the transcriptome of circulating EVs is enriched for tumor-associated transcripts, captures certain patient and tumor features, and reflects on-therapy tumor adaptation changes. Altogether, we show that EV profiling enables longitudinal transcriptomic and genomic profiling of mPC in liquid biopsy.
Sujet(s)
Vésicules extracellulaires , Génomique , Tumeurs de la prostate , Transcriptome , Mâle , Humains , Tumeurs de la prostate/génétique , Tumeurs de la prostate/anatomopathologie , Tumeurs de la prostate/sang , Vésicules extracellulaires/génétique , Vésicules extracellulaires/métabolisme , Génomique/méthodes , Animaux , Analyse de profil d'expression de gènes/méthodes , Métastase tumorale , Souris , Marqueurs biologiques tumoraux/génétique , Marqueurs biologiques tumoraux/sang , Biopsie liquide/méthodes , ADN tumoral circulant/génétique , ADN tumoral circulant/sang , Régulation de l'expression des gènes tumoraux , Lignée cellulaire tumoraleRÉSUMÉ
BACKGROUND: This is a preliminary study of a specific nutritional supplement -Supportan(®) - for the clinical support of patients with locally advanced head and neck (H&N) cancers who underwent treatment with concurrent radiochemotherapy (RT-CHT). MATERIAL AND METHODS: Seven patients received nutritional supplement (Supportan(®)) plus habitual diet during a median time of treatment with RT on 7.8 weeks plus concurrent weekly CHT(S). Specific serum protein fractions as a potential useful tool to evaluate the nutritional status were determined. The main objective was to assess the compliance with the above-mentioned treatment. RESULTS: Patients completed the nutritional support, 5 / 7 patients via oral route and 2/7 patients through nasogastric tube. All studied patients, that completed treatment, had not severe mucositis -ulcera, hemrraghe and/ or infection. None of them had another severe toxicity by treatment nor had impairment of Pefomance Status. No differences in all specific sera proteins were observed between S and To. CONCLUSION: In this preliminary study of few patients, we have observed a potential usefulness of Supportan(®) in the compliance of concurrent RT-CHT in patients with H&N cancers; moreover, its administration was useful to maintain the initial biochemical nutritional profile.