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A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
Cell death-related molecules and biomarkers for renal cell carcinoma targeted therapy
Yongchang Lai1, Tao Zeng1, Xiongfa Liang1
1Department of Urology, Minimally Invasive Surgery Center, Guangdong Key Laboratory of Urology, Guangzhou Urology Research Institute, The First Affiliated Hospital of Guangzhou Medical University, Kangda Road 1#, Haizhu District, Guangzhou, 510230 Guangdong China.
Abstract:
Renal cell carcinoma (RCC) is not sensitive to conventional radio- and chemotherapies and is at least partially resistant to impairments in cell death-related signaling pathways. The hallmarks of RCC formation include diverse signaling pathways, such as maintenance of proliferation, cell death resistance, angiogenesis induction, immune destruction avoidance, and DNA repair. RCC diagnosed during the early stage has the possibility of cure with surgery. For metastatic RCC (mRCC), molecular targeted therapy, especially antiangiogenic therapy (e.g., tyrosine kinase inhibitors, TKIs, such as sunitinib), is one of the main partially effective therapeutics. Various forms of cell death that may be associated with the resistance to targeted therapy because of the crosstalk between targeted therapy and cell death resistance pathways were originally defined and differentiated into apoptosis, necroptosis, pyroptosis, ferroptosis and autophagic cell death based on cellular morphology. Particularly, as a new form of cell death, T cell-induced cell death by immune checkpoint inhibitors expands the treatment options beyond the current targeted therapy. Here, we provide an overview of cell death-related molecules and biomarkers for the progression, prognosis and treatment of mRCC by targeted therapy, with a focus on apoptosis and T cell-induced cell death, as well as other forms of cell death.
Insights
Metastatic renal cell carcinoma (mRCC) resists conventional treatments. Understanding cell death pathways, including T cell-induced death, is key for developing new targeted therapies beyond tyrosine kinase inhibitors.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Renal cell carcinoma (RCC) exhibits resistance to traditional radio- and chemotherapy.
- Hallmarks of RCC include sustained proliferation, resistance to cell death, and immune evasion.
- Metastatic RCC (mRCC) is primarily treated with molecular targeted therapies, notably antiangiogenic agents like tyrosine kinase inhibitors (TKIs).
Purpose of the Study:
- To review cell death-related molecules and biomarkers in mRCC.
- To focus on apoptosis and T cell-induced cell death in the context of targeted therapy resistance.
- To explore other forms of cell death relevant to mRCC treatment.
Main Methods:
- Literature review of cell death mechanisms in mRCC.
- Analysis of signaling pathways involved in targeted therapy resistance.
- Examination of biomarkers for progression, prognosis, and treatment response.
Main Results:
- mRCC is characterized by complex signaling pathways contributing to treatment resistance.
- Targeted therapies like TKIs show partial effectiveness but face resistance due to crosstalk with cell death pathways.
- Emerging T cell-induced cell death offers new therapeutic avenues beyond current targeted treatments.
Conclusions:
- Cell death pathways, including apoptosis and T cell-mediated cytotoxicity, are critical in mRCC.
- Identifying specific cell death molecules and biomarkers can improve mRCC prognosis and treatment strategies.
- Further research into diverse cell death mechanisms is essential for advancing mRCC therapy.
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