Therapeutic Strategies for Patients With Metastatic Renal Cell Carcinoma in Whom First-Line Vascular Endothelial Growth Factor Receptor–Directed Therapies Fail

Malouf, Gabriel G.; Flippot, Ronan; Khayat, David

doi:10.1200/jop.2016.011809

Cited by 11 publications

(10 citation statements)

References 68 publications

(66 reference statements)

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“…These pathways are associated with key angiogenesis events that include cell proliferation, migration, survival, and vascular permeability (Roskoski, 2017). In patients with ccRCC being treated with VEGF and mTOR blockers, angiogenesis can be stimulated by angiopoietin 2, c-MET, or interleukin (Malouf et al, 2016).…”

Section: Molecular Mechanisms In Hypoxia and Angiogenesis In Ccrcc: Tmentioning

confidence: 99%

Molecular Mechanisms in Clear Cell Renal Cell Carcinoma: Role of miRNAs and Hypermethylated miRNA Genes in Crucial Oncogenic Pathways and Processes

et al. 2019

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Clear cell renal cell carcinoma (ccRCC) is the third most common urological cancer, and it has the highest mortality rate. The increasing drug resistance of metastatic ccRCC has resulted in the search for new biomarkers. Epigenetic regulatory mechanisms, such as genome-wide DNA methylation and inhibition of protein translation by interaction of microRNA (miRNA) with its target messenger RNA (mRNA), are deeply involved in the pathogenesis of human cancers, including ccRCC, and may be used in its diagnosis and prognosis. Here, we review oncogenic and oncosuppressive miRNAs, their putative target genes, and the crucial pathways they are involved in. The contradictory behavior of a number of miRNAs, such as suppressive and anti-metastatic miRNAs with oncogenic potential (for example, miR-99a, miR-106a, miR-125b, miR-144, miR-203, miR-378), is examined. miRNAs that contribute mostly to important pathways and processes in ccRCC, for instance, PI3K/AKT/mTOR, Wnt-β, histone modification, and chromatin remodeling, are discussed in detail. We also separately consider their participation in crucial oncogenic processes, such as hypoxia and angiogenesis, metastasis, and epithelial-mesenchymal transition (EMT). The review also considers the interactions of long non-coding RNAs (lncRNAs) and miRNAs of significance in ccRCC. Recent advances in the understanding of the role of hypermethylated miRNA genes in ccRCC and their usefulness as biomarkers are reviewed based on our own data and those available in the literature. Finally, new data and perspectives concerning the clinical applications of miRNAs in the diagnosis, prognosis, and treatment of ccRCC are discussed.

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Section: Molecular Mechanisms In Hypoxia and Angiogenesis In Ccrcc: Tmentioning

confidence: 99%

Molecular Mechanisms in Clear Cell Renal Cell Carcinoma: Role of miRNAs and Hypermethylated miRNA Genes in Crucial Oncogenic Pathways and Processes

et al. 2019

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“…Retrospective data showed that in patients previously treated with nivolumab, TKIs remain active in subsequent lines of treatment, which supports the use of cabozantinib after immune checkpoint inhibitors [Albiges et al 2015;Malouf et al 2016]. Currently we lack biomarkers in advanced RCC or mRCC to select the best treatment option for patients and we base our treatment selection on a patient's relative contraindications to certain therapy, the results of clinical trials, and subgroup analyses to guide the therapy decision.…”

Section: Cabozantinib In the Third-line Settingmentioning

confidence: 99%

Cabozantinib in the treatment of advanced renal cell carcinoma: clinical trial evidence and experience

Ruíz-Morales

Heng

2016

Therapeutic Advances in Urology

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Abstract:The treatment of metastatic renal cell carcinoma (mRCC) is rapidly changing. During first-line treatment with targeted therapy, patients ultimately develop resistance to therapy and the disease progresses. Recently, cabozantinib has demonstrated a better response rate, progression-free survival and overall survival compared with everolimus after failure of prior targeted therapy in patients with advanced or metastatic renal cell carcinoma (RCC). Cabozantinib is a small-molecule tyrosine kinase inhibitor (TKI). It exerts inhibition of MET, vascular endothelial growth factor receptor type 2, AXL, and many other receptor tyrosine kinases that are also implicated in tumor pathobiology, including RET, KIT, and FLT3. MET drives tumor survival, invasion, angiogenesis, and metastasis through several downstream signaling pathways. AXL has recently been described as an essential mediator of cancer metastasis that mediates crosstalk and resistance to TKIs. MET and AXL are thought to be anti-vascular endothelial growth factor receptor (VEGF) resistance pathways and thus cabozantinib represents a logical choice after progression on initial VEGF therapy. Subgroup analyses examining those with good performance status or visceral and bone metastases indicate that the hazard ratios may be better when using cabozantinib versus everolimus. However, there were no clear statistically significant differences between any subgroups.

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“…Clinical trials to evaluate such specific subpopulations need further evaluation. Finally, the approval of the immune checkpoint inhibitor nivolumab as second line in mC-CRCC treatment also introduces complexity in the choice of the best sequence (Malouf et al, 2016).…”

Section: Choice Of Pki For Mccrccmentioning

confidence: 99%

Clinical pharmacology of anti-angiogenic drugs in oncology

Gougis

Wassermann²,

Spano

et al. 2017

Critical Reviews in Oncology/Hematology

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Abnormal vasculature proliferation is one of the so-called hallmarks of cancer. Angiogenesis inhibitor therapies are one of the major breakthroughs in cancer treatment in the last two decades. Two types of anti-angiogenics have been approved: monoclonal antibodies and derivatives, which are injected and target the extracellular part of a receptor, and protein kinase inhibitors, which are orally taken small molecules targeting the intra-cellular Adenosine Triphosphate -pocket of different kinases. They have become an important part of some tumors' treatment, both in monotherapy or in combination. In this review, we discuss the key pharmacological concepts and the major pitfalls of anti-angiogenic prescriptions. We also review the pharmacokinetic and pharmacodynamics profile of all approved anti-angiogenic protein kinase inhibitors and the potential role of surrogate markers and of therapeutic drug monitoring.

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Therapeutic Strategies for Patients With Metastatic Renal Cell Carcinoma in Whom First-Line Vascular Endothelial Growth Factor Receptor–Directed Therapies Fail

Cited by 11 publications

References 68 publications

Molecular Mechanisms in Clear Cell Renal Cell Carcinoma: Role of miRNAs and Hypermethylated miRNA Genes in Crucial Oncogenic Pathways and Processes

Molecular Mechanisms in Clear Cell Renal Cell Carcinoma: Role of miRNAs and Hypermethylated miRNA Genes in Crucial Oncogenic Pathways and Processes

Cabozantinib in the treatment of advanced renal cell carcinoma: clinical trial evidence and experience

Clinical pharmacology of anti-angiogenic drugs in oncology

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