A decade of pharmacogenomics research on tyrosine kinase inhibitors in metastatic renal cell cancer: a systematic review

Diekstra, Meta H.M.; Swen, Jesse J.; Gelderblom, Hans; Guchelaar, Henk‐Jan

doi:10.1586/14737159.2016.1148601

Cited by 20 publications

(32 citation statements)

References 79 publications

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“…Thus, identification of a specific biomarker is essential to allow for early detection. Moreover, RCC is characterized by high chemo- and radio-resistance, limiting the efficacy of the few treatment options, while targeted therapies have demonstrated a survival benefit [109]. RCC metabolic signature is characterized by alterations in energy metabolism pathways, among which are FAs’ catabolism pathways, with essential implications in cell growth and proliferation [110].…”

Section: Lipidomics In Cancer Researchmentioning

confidence: 99%

Advances in Lipidomics for Cancer Biomarkers Discovery

Perrotti

Rosa

Cicalini

et al. 2016

IJMS

161

119

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Lipids play critical functions in cellular survival, proliferation, interaction and death, since they are involved in chemical-energy storage, cellular signaling, cell membranes, and cell–cell interactions. These cellular processes are strongly related to carcinogenesis pathways, particularly to transformation, progression, and metastasis, suggesting the bioactive lipids are mediators of a number of oncogenic processes. The current review gives a synopsis of a lipidomic approach in tumor characterization; we provide an overview on potential lipid biomarkers in the oncology field and on the principal lipidomic methodologies applied. The novel lipidomic biomarkers are reviewed in an effort to underline their role in diagnosis, in prognostic characterization and in prediction of therapeutic outcomes. A lipidomic investigation through mass spectrometry highlights new insights on molecular mechanisms underlying cancer disease. This new understanding will promote clinical applications in drug discovery and personalized therapy.

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Section: Lipidomics In Cancer Researchmentioning

confidence: 99%

Advances in Lipidomics for Cancer Biomarkers Discovery

Perrotti

Rosa

Cicalini

et al. 2016

IJMS

161

119

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“…These have an affinity for the ATP‐binding site of RTKs, but bind irreversibly by covalently bonding . As a result, a generalized class effect cannot be inferred for the influence of small molecule TKIs on outcome, efficacy, or cardiovascular toxicity …”

Section: Small Molecule Tyrosine Kinase Inhibitor‐induced Cardiovascumentioning

confidence: 99%

Cardiovascular Toxicities of Small Molecule Tyrosine Kinase Inhibitors: An Opportunity for Systems‐Based Approaches

Brown

Nhola

Herrmann

2016

Clin Pharma and Therapeutics

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Once universally considered a rapidly fatal condition, cancer has increasingly become a chronic medical condition and comorbidities and adverse effects of cancer therapies have become increasingly significant. One of the leading advancements that has gained traction for the treatment of a variety of malignancies is the class of small molecule tyrosine kinase inhibitors (TKIs). Although, in many aspects revolutionary, TKIs have their own profile of side effects, including cardiovascular side effects, the most common being hypertension (HTN), congestive heart failure, corrected QT (QTc) prolongation, and instances of premature coronary heart disease. Herein, we describe the mechanisms of small TKI-induced cardiovascular toxicity and related intracellular signaling. In particular, systems-based approaches to the understanding of small TKI-induced cardiovascular toxicity are addressed. The pathophysiology of synergic cardiovascular toxicity from TKIs, anthracyclines, and monoclonal antibodies (e.g., trastuzumab, bevacizumab) is illustrated. Finally, recommendations are made for implementing systems medicine in clinical practice, for individualized cardiovascular wellness after cancer therapy.

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“…The impact of these SNPs on the efficacy and safety of tyrosine kinase inhibitors range from modulating pharmacokinetics (e.g., through increased drug clearance) through to pharmacodynamics (e.g., increased expression of target proteins), and/or activation of downstream signaling pathways (15–29). With regards to SNPs in VEGF and VEGF receptors (VEGFR)-1, 2, or 3, various studies and analyses have reported that certain SNPs are associated with poorer response rate, overall survival (OS), and/or progression-free survival (PFS) in patients with metastatic RCC treated with sunitinib (19, 20, 24–29).…”

Section: Introductionmentioning

confidence: 99%

Phase III Trial of Adjuvant Sunitinib in Patients with High-Risk Renal Cell Carcinoma: Exploratory Pharmacogenomic Analysis

George

Martini

Staehler

et al. 2019

Clinical Cancer Research

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Background: In the S-TRAC trial, adjuvant sunitinib prolonged disease-free survival (DFS) versus placebo in patients with loco-regional renal cell carcinoma at high risk of recurrence after nephrectomy. An exploratory analysis evaluated associations between single nucleotide polymorphisms (SNPs) in several angiogenesis- or hypoxia-related genes and clinical outcomes in S-TRAC. Methods: Blood samples were genotyped for 10 SNPs and one insertion/deletion mutation using TaqMan assays. DFS was compared using log-rank tests for each genotype in sunitinib versus placebo groups and between genotypes within each of three (sunitinib, placebo, and combined sunitinib plus placebo) treatment groups. P-values were unadjusted. Results: In all, 286 patients (sunitinib, n=142; placebo, n=144) were genotyped. Longer DFS (HR [95% confidence interval]) was observed with sunitinib versus placebo for VEGFR1 rs9554320 C/C (0.44 [0.21–0.91]; P=0.023), VEGFR2 rs2071559 T/T (0.46 [0.23–0.90]; P=0.020), and eNOS rs2070744 T/T (0.53 [0.30–0.94]; P=0.028). Shorter DFS was observed for VEGFR1 rs9582036 C/A versus C/C with sunitinib, placebo, and combined therapies (P≤0.05), and A/A vs C/C with sunitinib (P=0.022). VEGFR1 rs9554320 A/C versus A/A was associated with shorter DFS in the placebo (P=0.038) and combined (P=0.006) groups. Conclusions: Correlations between VEGFR1 and VEGFR2 SNPs and longer DFS with sunitinib suggest germline SNPs are predictive of improved outcomes with adjuvant sunitinib in patients with renal cell carcinoma. Independent validation studies are needed to confirm these findings.

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A decade of pharmacogenomics research on tyrosine kinase inhibitors in metastatic renal cell cancer: a systematic review

Cited by 20 publications

References 79 publications

Advances in Lipidomics for Cancer Biomarkers Discovery

Advances in Lipidomics for Cancer Biomarkers Discovery

Cardiovascular Toxicities of Small Molecule Tyrosine Kinase Inhibitors: An Opportunity for Systems‐Based Approaches

Phase III Trial of Adjuvant Sunitinib in Patients with High-Risk Renal Cell Carcinoma: Exploratory Pharmacogenomic Analysis

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