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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
New insights into the management of renal cell cancer
Nicolas Pécuchet1, Laure S Fournier, Stéphane Oudard
1Department of Medical Oncology, Hôpital Européen Georges Pompidou, Paris, France.
Abstract:
Kidney cancer is composed of several bio-histological entities. The most frequent type, clear-cell carcinoma, is not homogenous regarding gene mutations or transcriptomic profiles, but the biologic classifications are not yet mature. Therefore, biologically driven strategies of treatment have not yet been developed in the clinical setting. The choice of first-line agent currently depends on the prognostic criteria published by Motzer et al. [J Clin Oncol 1999;17:2530-2540] and recently by Heng et al. [J Clin Oncol 2009;27:5794-5799], with anti-vascular endothelial growth factor (VEGF) therapies for good- or intermediate-prognosis groups and anti-mammalian target of rapamycin (mTOR) for poor-risk patients. In the past years, biological changes leading to resistance to targeted agents have been widely investigated. Discoveries resulted in the development of second-generation VEGF receptor tyrosine kinase inhibitors, characterized by an improved potency and selectivity. Besides, co-inhibition of signalling pathways mediating resistance to anti-VEGF are being developed targeting fibroblast growth factor and c-Met. Dual mTOR/phosphatidylinositol 3-kinase inhibitors have greater efficacy than rapalogs in preclinical models and are being investigated in early clinical trials. In conclusion, the changing landscape in the biology and treatment of kidney cancer offers new opportunities for clinicians to treat patients, but, due to relatively high costs, the use of targeted therapies will likely be strongly controlled by health authorities.
Insights
Kidney cancer treatment is evolving, with new targeted therapies emerging. Current choices rely on prognostic criteria, but future strategies will be biologically driven, balancing efficacy and cost.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Kidney cancer comprises diverse bio-histological subtypes, with clear-cell carcinoma being the most common.
- Current treatment strategies for kidney cancer are not yet fully biologically driven due to immature biologic classifications.
- First-line treatment selection relies on prognostic criteria, guiding the use of anti-vascular endothelial growth factor (VEGF) and anti-mammalian target of rapamycin (mTOR) therapies.
Purpose of the Study:
- To review the evolving landscape of kidney cancer biology and targeted therapies.
- To discuss the development of novel therapeutic strategies addressing resistance mechanisms.
- To highlight the potential impact of new treatments on clinical practice and healthcare costs.
Main Methods:
- Literature review of recent advancements in kidney cancer research.
- Analysis of emerging targeted agents and their mechanisms of action.
- Discussion of clinical trial data for novel therapeutic combinations.
Main Results:
- Resistance to targeted agents has spurred the development of next-generation inhibitors (e.g., selective VEGF receptor tyrosine kinase inhibitors).
- Co-inhibition strategies targeting pathways like fibroblast growth factor and c-Met are under investigation.
- Dual mTOR/phosphatidylinositol 3-kinase inhibitors show promise in preclinical models and early clinical trials.
Conclusions:
- The dynamic changes in kidney cancer biology and treatment offer new clinical opportunities.
- Future treatments may involve combination therapies targeting multiple signaling pathways.
- High costs of targeted therapies necessitate careful consideration and may lead to stringent health authority controls.
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