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Combinatorial and Sequential Targeted Therapy in Metastatic Renal Cell Carcinoma

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Kidney Cancer

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Abstract

Greater insight into the biology of renal cell carcinoma (RCC) has expanded treatment options in metastatic RCC (mRCC). Since 2005, seven targeted agents have been approved by the US Food and Drug Administration (US FDA) for the management of mRCC, but little evidence exists on combining these therapies together or with novel agents, traditional immunotherapies, or chemotherapeutic drugs.

In theory, combining targeted therapies may provide more complete blockade of aberrant signaling ultimately leading to the potential for additive or synergistic effects. Concomitant targeted therapies may also have the potential to combat resistance that inevitably emerge with single-agent targeted therapies over time. Evidence suggests that resistance is mediated by changes which arise within the tumor and in its surrounding microenvironment. Such changes allow for continued proliferation and growth independent of VEGF. It is hypothesized that signaling upstream of receptor blockade could also drive tumor growth independent of usual aberrant proliferative pathways.

Greater insight into the biology of renal cell carcinoma (RCC) has expanded treatment options in metastatic RCC (mRCC). Since 2005, seven targeted agents have been approved by the US Food and Drug Administration (US FDA) for the management of mRCC, but little evidence exists on combining these therapies together or with novel agents, traditional immunotherapies, or chemotherapeutic drugs. In theory, combining targeted therapies may provide more complete blockade of aberrant signaling ultimately leading to the potential for additive or synergistic effects. Concomitant targeted therapies may also have the potential to combat resistance that inevitably emerge with single-agent targeted therapies over time. Evidence suggests that resistance is mediated by changes which arise within the tumor and in its surrounding microenvironment. Such changes allow for continued proliferation and growth independent of VEGF. It is hypothesized that signaling upstream of receptor blockade could also drive tumor growth independent of usual aberrant proliferative pathways. Research is ongoing to define the optimal combinations and/or sequences of these drugs with novel therapies such as anti-PD-1 and anti-PD-L1 therapies

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Authors and Affiliations

  1. Hematology/Oncology, The Gayle and Tom Benson Cancer Center, Ochsner Medical Center, New Orleans, LA, USA

    Marc R. Matrana MD, Msc

  2. Division of Pharmacy, Clinical Pharmacy Services, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    Bradley J. Atkinson Pharm.D

  3. Division of Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    Nizar M. Tannir MD

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  1. Marc R. Matrana MD, Msc
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  3. Nizar M. Tannir MD
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Correspondence to Marc R. Matrana MD, Msc .

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  1. Department of Internal Medicine, Division of Hematology - Oncology, University of California Davis, School of Medicine UC Davis Comprehensive Cancer center, Sacramento, California, USA

    Primo N. Lara

  2. Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA

    Eric Jonasch

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Matrana, M.R., Atkinson, B.J., Tannir, N.M. (2015). Combinatorial and Sequential Targeted Therapy in Metastatic Renal Cell Carcinoma. In: Lara, P., Jonasch, E. (eds) Kidney Cancer. Springer, Cham. https://doi.org/10.1007/978-3-319-17903-2_19

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