RESUMEN
BACKGROUND: Liquid biopsies of blood plasma cell free DNA can be used to monitor treatment response and potentially detect mutations that are present in resistant clones in metastatic cancer patients. CASE PRESENTATION: In our non-interventional liquid biopsy study, a male patient in his fifties diagnosed with stage IV colorectal cancer and polytope liver metastases rapidly progressed after completing chemotherapy and deceased 8 months after diagnosis. Retrospective cell free DNA testing showed that the APC/TP53/KRAS major clone responded quickly after 3 cycles of FOLFIRI + Bevacizumab. Retrospective exome sequencing of pre-chemotherapy and post-chemotherapy tissue samples including metastases confirmed that the APC/TP53/KRAS and other major clonal mutations (GPR50, SLC5A, ZIC3, SF3A1 and others) were present in all samples. After the last chemotherapy cycle, CT imaging, CEA and CA19-9 markers validated the cfDNA findings of treatment response. However, 5 weeks later, the tumour had rapidly progressed. CONCLUSION: As FOLFIRI+Bevacizumab has recently also been associated with sustained complete remission in a APC/TP53/KRAS triple-mutated patient, these driver genes should be tested and monitored in a more in-depth manner in future patients. Patients with metastatic disease should be monitored more closely during and after chemotherapy, ideally using cfDNA.
Asunto(s)
Proteína de la Poliposis Adenomatosa del Colon/sangre , Neoplasias Colorrectales/tratamiento farmacológico , Proteínas Proto-Oncogénicas p21(ras)/sangre , Proteína p53 Supresora de Tumor/sangre , Proteína de la Poliposis Adenomatosa del Colon/genética , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab/administración & dosificación , Bevacizumab/efectos adversos , Camptotecina/administración & dosificación , Camptotecina/efectos adversos , Camptotecina/análogos & derivados , Ácidos Nucleicos Libres de Células/sangre , ADN Tumoral Circulante/sangre , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Biopsia Líquida , Masculino , Persona de Mediana Edad , Mutación , Metástasis de la Neoplasia , Proteínas Proto-Oncogénicas p21(ras)/genética , Inducción de Remisión , Proteína p53 Supresora de Tumor/genéticaRESUMEN
Animals are usually regarded as independent entities within their respective environments. However, within an organism, eukaryotes and prokaryotes interact dynamically to form the so-called metaorganism or holobiont, where each partner fulfils its versatile and crucial role. This review focuses on the interplay between microorganisms and multicellular eukaryotes in the context of host physiology, in particular aging and mucus-associated crosstalk. In addition to the interactions between bacteria and the host, we highlight the importance of viruses and nonmodel organisms. Moreover, we discuss current culturing and computational methodologies that allow a deeper understanding of underlying mechanisms controlling the physiology of metaorganisms.