Cell death-based approaches in treatment of the urinary tract-associated diseases: a fight for survival in the killing fields
| Autor: | Alberto Ortiz, Carmen González-Enguita, Maria Dolores Sanchez-Niño, Ana Belen Sanz, Miguel Fontecha-Barriuso, Adrian M. Ramos, Ramiro Cabello, Diego Martin-Sanchez, Andreas Linkermann |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research Programmed cell death Cell Survival Necroptosis medicine.medical_treatment Immunology Apoptosis Review Article 03 medical and health sciences Cellular and Molecular Neuroscience Prostate cancer 0302 clinical medicine Immune system medicine Animals Humans lcsh:QH573-671 Cytoskeleton lcsh:Cytology business.industry Cancer Cell Biology Immunotherapy medicine.disease 030104 developmental biology 030220 oncology & carcinogenesis Urinary Tract Infections Cancer cell Cancer research business Signal Transduction |
| Zdroj: | Cell Death and Disease, Vol 9, Iss 2, Pp 1-14 (2018) Cell Death & Disease |
| ISSN: | 2041-4889 |
| DOI: | 10.1038/s41419-017-0043-2 |
| Popis: | Urinary tract-associated diseases comprise a complex set of disorders with a variety of etiologic agents and therapeutic approaches and a huge global burden of disease, estimated at around 1 million deaths per year. These diseases include cancer (mainly prostate, renal, and bladder), urinary tract infections, and urolithiasis. Cell death plays a key role in the pathogenesis and therapy of these conditions. During urinary tract infections, invading bacteria may either promote or prevent host cell death by interfering with cell death pathways. This has been studied in detail for uropathogenic E. coli (UPEC). Inhibition of host cell death may allow intracellular persistence of live bacteria, while promoting host cell death causes tissue damage and releases the microbes. Both crystals and urinary tract obstruction lead to tubular cell death and kidney injury. Among the pathomechanisms, apoptosis, necroptosis, and autophagy represent key processes. With respect to malignant disorders, traditional therapeutic efforts have focused on directly promoting cancer cell death. This may exploit tumor-specific characteristics, such as targeting Vascular Endothelial Growth Factor (VEGF) signaling and mammalian Target of Rapamycin (mTOR) activity in renal cancer and inducing survival factor deprivation by targeting androgen signaling in prostate cancer. An area of intense research is the use of immune checkpoint inhibitors, aiming at unleashing the full potential of immune cells to kill cancer cells. In the future, this may be combined with additional approaches exploiting intrinsic sensitivities to specific modes of cell death such as necroptosis and ferroptosis. Here, we review the contribution of diverse cell death mechanisms to the pathogenesis of urinary tract-associated diseases as well as the potential for novel therapeutic approaches based on an improved molecular understanding of these mechanisms. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|