Interleukin-6 (IL-6) is a cytokine with multifaceted effects playing a remarkable role in the initiation of the immune response. The increased level of this cytokine in the elderly seems to be associated with the chronic inflammatory setting of the microenvironment in aged individuals. IL-6 also represents one of the main signals in communication between cancer cells and their non-malignant neighbours within the tumour niche. IL-6 also participates in the development of a premetastatic niche and in the adjustment of the metabolism in terminal-stage patients suffering from a malignant disease. IL-6 is a fundamental factor of the cytokine storm in patients with severe COVID-19, where it is responsible for the fatal outcome of the disease. A better understanding of the role of IL-6 under physiological as well as pathological conditions and the preparation of new strategies for the therapeutic control of the IL-6 axis may help to manage the problems associated with the elderly, cancer, and serious viral infections.
- MeSH
- COVID-19 MeSH
- interleukin-6 genetika metabolismus MeSH
- koronavirové infekce metabolismus patologie MeSH
- lidé MeSH
- nádory metabolismus patologie MeSH
- pandemie MeSH
- signální transdukce MeSH
- stárnutí metabolismus patologie MeSH
- virová pneumonie metabolismus patologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The precision medicine (PM) initiative is a response to the dismal outlook in solid cancer. Despite heterogeneity, common mechanistic denominators may exist across the spectrum of solid cancer. A shift from conventional research and development (R&D) toward PM will require conceptual and structural change. As individuals and as a society, we welcome innovation, but question change. We ask: In solid cancer, does PM identify and address the causes of prior failures, and, if so, are the proposed solutions feasible? And, when may we expect safer, more effective and affordable drugs in the clinic? Considerations that prompt a pragmatic rethink include a failure analysis of translational R&D in solid cancer suggesting that trials and regulations need to be aligned with the natural history of the disease. In successful therapeutic interventions in chronic, complex disease, surrogate markers and endpoints should be consistent with the Prentice's criteria. In solid cancer, drug induced tumor shrinkage, is a drug effect and not a disease response; tumor shrinkage does not reflect nor predict interruption of the disease. Overall, we support a pragmatic, multidisciplinary, and collaborative R&D, and suggest that direction be set by clinical need and utility, and by questions, not answers. PM will prove worthwhile if it could improve clinical outcomes. The lag in therapeutics relative to diagnostics is a cause for confusion. Overdiagnosis adds to fear and harm, especially in the absence of effective interventions. A revised initiative that prioritizes metastasis research could replicate the successful HIV/AIDS model in solid cancer. A pragmatic approach may further translational efforts toward meaningfully effective, generally available, and affordable solutions.
- Publikační typ
- časopisecké články MeSH
- Klíčová slova
- améboidní invazivita, mezenchymální invazivita,
- MeSH
- inhibitory proteas terapeutické užití MeSH
- invazivní růst nádoru * MeSH
- kinázy asociované s rho antagonisté a inhibitory účinky léků MeSH
- lidé MeSH
- metastázy nádorů * farmakoterapie patologie MeSH
- nádorové mikroprostředí MeSH
- nádory enzymologie farmakoterapie komplikace MeSH
- podozomy MeSH
- proteasy účinky léků MeSH
- Check Tag
- lidé MeSH
