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Immunotherapy in Renal Cell Carcinoma: The Future Is Now.

ABSTRACT: Renal cell carcinoma is the third type of urologic cancer and has a poor prognosis with 30% of metastatic patients at diagnosis. The antiangiogenics and targeted immunotherapies led to treatment remodeling emphasizing the role of the tumour microenvironment. However, long-term responses are rare with a high rate of resistance. New strategies are emerging to improve the efficacy and the emerging drugs are under evaluation in ongoing trials. With the different treatment options, there is an urgent need to identify biomarkers in order to predict the efficacy of drugs and to better stratify patients. Owing to the limitations of programmed death-ligand 1 (PD-L1), the most studied immunohistochemistry biomarkers, and of the tumor mutational burden, the identification of more reliable markers is an unmet need. New technologies could help in this purpose.

SUBMITTER: Deleuze A

PROVIDER: S-EPMC7177761 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Immunotherapy in Renal Cell Carcinoma: The Future Is Now.

Deleuze Antoine A Saout Judikaël J Dugay Frédéric F Peyronnet Benoit B Mathieu Romain R Verhoest Gregory G Bensalah Karim K Crouzet Laurence L Laguerre Brigitte B Belaud-Rotureau Marc-Antoine MA Rioux-Leclercq Nathalie N Kammerer-Jacquet Solène-Florence SF

International journal of molecular sciences 20200405 7

Renal cell carcinoma is the third type of urologic cancer and has a poor prognosis with 30% of metastatic patients at diagnosis. The antiangiogenics and targeted immunotherapies led to treatment remodeling emphasizing the role of the tumour microenvironment. However, long-term responses are rare with a high rate of resistance. New strategies are emerging to improve the efficacy and the emerging drugs are under evaluation in ongoing trials. With the different treatment options, there is an urgent ...[more]

PMID: 32260578

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Project description:Genitourinary (GU) cancers are a group of epithelial malignancies associated with the organs involved in the excretion of urine. Renal cell, urothelial, and prostatic carcinoma are the overwhelming subtypes diagnosed by oncologists. Each of these was traditionally treated surgically when local and non-invasive. When these carcinomas spread, invade, or metastasize, surgical control lacks in efficacy. Chemotherapeutic regimens have been implemented for decades and have increased overall survival but many patients progress. Molecular targeting through tyrosine kinase inhibition of the vascular endothelial growth factor (VEGF) has emerged as a frontline therapy in kidney cancer with more durable responses. More recently, immunotherapy has begun to find efficacy in many other solid tumors including melanoma and non-small cell lung cancer. The inherent genetic instability of this group of cancers makes them ideal solid tumors for immune modulation. Vaccines manufactured to initiate T-Cell regulation through neoplastic-antigen presentation are available for prostate cancer and are currently on trial in renal cell carcinoma (RCC). Programmed death-1 (PD-1) and its ligand (PD-L1) are intricate members of cellular immunity against neoplastic cells. In an activated, unbound state, these molecules permit T-cell activation and cytotoxic killing of cancer cells. However, when they are linked, cellular immunity is attenuated and local cancer cells are permitted the opportunity to proliferate and invade. A novel class of monoclonal antibodies have been developed which stop PD-1 linkage and thus uncouple the 'stop' signal of these neoplastic regulatory cells. The increased overall and progression free survival have made them attractive options alone as well as in combination with anti-VEGF inhibitors for patients. Although more tolerable than chemotherapy, immunotherapeutics have adverse potential toxicities. Overall, the use of immunomodulatory medications have opened a new paradigm in the anti-neoplastic regimen of GU cancers and further developments will determine the appropriate patient to treat for optimum tumor burden eradication.

Dataset Information

Immunotherapy in Renal Cell Carcinoma: The Future Is Now.

Publications

Immunotherapy in Renal Cell Carcinoma: The Future Is Now.

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