Search results for "Sunitinib"

Conquests and perspectives of cardio-oncology in the field of tumor angiogenesis-targeting tyrosine kinase inhibitor-based therapy

2015

Abstract: Introduction: Angiogenesis is fundamental for tumor development and progression. Hence, anti-angiogenic drugs have been developed to target VEGF and its receptors (VEGFRs). Several tyrosine kinase inhibitors (TKIs) have been developed over the years and others are still under investigation, each anti-VEGFR TKI showing a different cardiotoxic profile. Knowledge of the cardiac side-effects of each drug and the magnitude of their expression and frequency can lead to a specific approach. Areas covered: This work reviews the mechanism of action of anti-VEGFR TKIs and the pathophysiological mechanisms leading to cardiotoxicity, followed by close examination of the most important drugs i…

Study of the role of “gatekeeper” mutations V654A and T670I of c-kit kinase in the interaction with inhibitors by means mixed molecular dynamics/dock…

2011

The over-expression of c-kit proto-oncogene has been reported in hematopoietic cells, small cell lung cancer, and gastrointestinal stromal tumors. The clinical importance of c-kit expression in tumors focused the research towards inhibitors of this tyrosine kinase. Imatinib (Gleevec®) was the first compound used in therapy, but mutations on c-kit led to reduced effectiveness or ineffectiveness of this treatment. Other compounds are likely to be effective against mutants, such as Sunitinib (Sutent®), but the need for new and most effective inhibitors against mutants is still critical. We report mixed Molecular Dynamics/Docking study with the aim to unveil the molecular mechanism involved in …

2021

Tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors predominate as first-line therapy options for renal cell carcinoma. When first-line TKI therapy fails due to resistance development, an optimal second-line therapy has not yet been established. The present investigation is directed towards comparing the anti-angiogenic properties of the TKIs, sorafenib and axitinib on human endothelial cells (HUVECs) with acquired resistance towards the TKI sunitinib. HUVECs were driven to resistance by continuously exposing them to sunitinib for six weeks. They were then switched to a 24 h or further six weeks treatment with sorafenib or axitinib. HUVEC growth, as well as angiogenesis (tube…

Osteonecrosis of jaw beyond antiresorptive (bone-targeted) agents: new horizons in oncology

2016

Introduction: Osteonecrosis of the jaw (ONJ) is a clinically important, potentially painful and debilitating condition, which can affect the quality of life of cancer patients. Since 2003, ONJ appeared as a Bisphosphonate(BP)-related class effect, and the term Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) was widespread. Areas Covered: Under discussion in this review is the fact that ONJ cases have been reported after treatment including antiangiogenic agents and other “targeted therapy”, with and without BPs. Consequently, the comprehensive term Medication-Related Osteonecrosis of the Jaw (MRONJ) has been introduced. The clinical aspects and the prognosis of ONJ associated with t…

Targeted Therapy in Gastrointestinal Stromal Tumors

2015

Advances in the understanding of the molecular mechanisms of gastrointestinal stromal tumors (GISTs) pathogenesis have resulted in the development of a treatment approach which has become a model of targeted therapy in oncology. The introduction of imatinib mesylate [inhibiting KIT/PDGFRA (platelet-derived growth factor receptor-α) and their downstream signaling cascade] has dramatically improved the therapy of advanced (inoperable and/or metastatic) GIST. Imatinib has now become the standard of care in the treatment of patients with advanced GIST and its efficacy has been proven also in adjuvant setting after resection of primary high-risk tumors. However, a majority of patients eventually…

Targeting a Targeted Drug: An Approach Toward Hypoxia-Activatable Tyrosine Kinase Inhibitor Prodrugs

2016

Tyrosine kinase inhibitors (TKIs), which have revolutionized cancer therapy over the past 15 years, are limited in their clinical application due to serious side effects. Therefore, we converted two approved TKIs (sunitinib and erlotinib) into 2-nitroimidazole-based hypoxia-activatable prodrugs. Kinetics studies showed very different stabilities over 24 h; however, fast reductive activation via E. coli nitroreductase could be confirmed for both panels. The anticancer activity and signaling inhibition of the compounds against various human cancer cell lines were evaluated in cell culture. These data, together with molecular docking simulations, revealed distinct differences in the impact of …

Review and update on drugs related to the development of osteonecrosis of the jaw

2019

Conflict of interest Conclusions of the working group on “New drugs related to the de-velopment of osteonecrosis of the jaw”. Spanish Society of Cranio-mandibular Dysfunction and Orofacial Pain and Spanish Society of Oral Medicine SEDCYDO-SEMO joint International Meeting: 30th SEDCYDO annual meeting & 15th SEMO Congress. Bilbao (Spain); June, 2019. [EN] Background: Medication-related osteonecrosis of the jaw (MRONJ) is a rare, but serious adverse effect of cer-tain drugs, of which bisphosphonates are the most widely known. This pathology is also associated with other medications such as the biologic antiresorptive agent, denosumab and some antiangiogenics such as sunitinib, bevacizumab or a…

New paradigms for dental prevention of medication related osteonecrosis of jaws (MRONJ)

2018

ONJ-Prevention of local osteonecrosis risk factors should be planned before and during the intake of associated drugs, according to new schedules. Secondary prevention requires a careful clinical oral examination, but also first level X-ray examinations and, when necessary, second level (CT) too. Three main risk factors of ostonecrosis of the jaws (ONJ) are recognised: (i) the type of ONJ-related medications: antiresorptive (e.g., Bisphosphonates, Denosumab) and antiangiogenic drugs (e.g., Bevacizumab, Sunitinib); (ii) the category of patient at MRONJ risk: cancer versus non-cancer patient; (iii) the typologies and timing of dental treatments (e.g., before, during, or after the drug adminis…

Liver transarterial chemoembolization and sunitinib for unresectable hepatocellular carcinoma: Results of the PRODIGE 16 study

2021

Summary Background Trans-arterial chemoembolization (TACE) is one first-line option therapy for patients with hepatocellular carcinoma (HCC) not suitable for surgical resection. Aims We evaluated the effects of sunitinib plus doxorubicin-TACE on bleeding or liver failure. Methods Seventy-eight patients with HCC were included in this randomized, double-blind study. They received one to three TACE plus either sunitinib or placebo four weeks out of six for one year. The occurrence of severe bleeding or liver failure was assessed during the week after the TACE. The safety and survival outcomes were evaluated. Results No bleeding complication was reported. One and two liver failures were respect…

Sunitinib related osteonecrosis of the jaw (SURONJ): a rare occurrence?

2015

Sir, Sunitinib is a drug approved in 2006 by the FDA for the treatment of renal cell carcinoma (RCC) and resistant gastrointestinal stromal tumor (GIST). The capillary endothelium is the first target of sunitinib: it blocks several pathways central to proliferation, migration, differentiation, neoangiogenesis, and invasion of cancer cells, including vascular endothelial growth factor receptors (VEGFRs), plateletderived growth factor receptors (PDGFR-α and PGRF-β), the stem cell factor receptor (c-Kit) and the Fms-like tyrosine kinase 3 (FLT3), and glial cell–derived neurotrophic factor receptor (RET), colony-stimulating factor type 1 (CSF-1R) [1, 2, 9]. In literature, several adverse effect…