pazopanib and Inflammation

Discoidin domain receptors (DDRs) are members of the transmembrane receptor tyrosine kinase (RTK) superfamily which are distinguished from others by the presence of a discoidin motif in the extracellular domain and their utilization of collagens as internal ligands. Two types of DDRs, DDR1 and DDR2, have been identified with distinct expression profiles and ligand specificities. These DDRs play important roles in the regulation of fundamental cellular process, such as proliferation, survival, differentiation, adhesion, and matrix remodeling. They have also been closely linked to a number of human diseases, including various fibrotic disorders, atherosclerosis, and cancer. As a consequence, DDRs have been considered as novel potential molecular targets for drug discovery and increasing efforts are being devoted to the identification of new small molecule inhibitors targeting the receptors. In this review, we offer a contemporary overview on the discovery of DDRs inhibitors and their potential medical application for the treatment of cancer and inflammation related disorders.

Topics: Amino Acid Sequence; Animals; Discoidin Domain Receptors; Drug Discovery; Humans; Inflammation; Ligands; Models, Molecular; Molecular Sequence Data; Neoplasms; Protein Conformation; Protein Kinase Inhibitors; Receptor Protein-Tyrosine Kinases; Receptors, Mitogen; Small Molecule Libraries

To identify prognostic inflammatory markers in metastatic renal cell carcinoma (mRCC) patients who received anti-vascular endothelial growth factor receptor (VEGFR) agents.. Observational study. Place and Duration of the Study: Department of Medical Oncology, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey, between January 2015 and December 2021.. A total of 110 patients with mRCC who received sunitinib or pazopanib for at least 3 months were enrolled. Hemogram, C-reactive protein (CRP) and albumin values of the patients, CRP to albumin ratio (CAR), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), prognostic nutrition index (PNI) and systemic inflammatory response indexes (SIRI) were calculated and recorded. Progression-free survival and overall survival analyses of the patients were performed using the Kaplan-Meier method. Cox regression method was used to identify prognostic factors. Variables found to be significant in univariate analysis were enrolled in multivariate analysis.. In the univariate analysis for median overall survival (mOS), whether or not surgery was applied as the primary treatment option, grade, lymphovascular invasion (LVI), International Metastatic RCC Database Consortium (IMDC) score, CAR, NLR, PLR, SII, PNI and SIRI were found to be statistically significant. Systemic inflammation markers (CAR, NLR, PLR, PNI, SII and SIRI) were found to be independent prognostic markers for mOS as a result of Cox multivariate analysis.. CAR, NLR, PLR, SII, PNI, and SIRI values measured before anti-VEGFR treatment in patients with mRCC may be of additional prognostic significance. These markers, which are calculated by using parameters that are always measured in routine practice, such as complete blood count (CBC), albumin, and CRP levels, are easy and inexpensive methods that give an idea about the course of the disease.. Sunitinib, Pazopanib, Renal cell carcinoma, Prognostic marker, Overall survival, Inflammatory.

Topics: C-Reactive Protein; Carcinoma, Renal Cell; Humans; Inflammation; Kidney Neoplasms; Neutrophils; Prognosis; Retrospective Studies; Sunitinib; Tyrosine Kinase Inhibitors

Metastatic renal cell carcinoma (mRCC) encompasses a heterogeneous group of neoplasms with distinct clinical behavior and prognoses. As a result of the increasing number of therapeutic options in the metastatic setting, it is crucial to improve prognostic stratification ability. We aimed to evaluate the prognostic value of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and combination platelet count and neutrophil lymphocyte ratio (COP-NLR) in patients with mRCC. We evaluated a cohort of mRCC patients treated with first-line pazopanib or sunitinib. Levels of NLR, PLR and COP-NLR were measured prior to systemic treatment and evaluated as prognostic predictors. Primary endpoint was overall survival (OS). Data from 276 patients were included, of which 54.7% received first-line pazopanib and 45.3%, sunitinib. Memorial Sloan-Kettering Cancer Center risk classification was intermediate and poor in 50% and 42.6% of patients, respectively. High NLR (> 3.5) was associated with inferior OS (median 9.6 vs 17.8 months, P < 0.001). A high PLR (> 200) was associated with inferior OS (median 10.3 vs 17 months, P = 0.002). The median OS in the COP-NLR 1, 2 and 3 groups were 19.0 months (95% CI 15.3-26.0), 13.1 months (95% CI 9.8-17.0) and 7.4 months (95% CI 3.6-11.9), respectively (P < 0.001). In the multivariate analysis, high NLR and high COP-NLR were associated with inferior OS. Both high NLR and high COP-NLR were associated with poorer OS in our cohort of patients with mRCC treated with first-line pazopanib or sunitinib.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Biomarkers, Tumor; Carcinoma, Renal Cell; Child; Female; Humans; Indazoles; Inflammation; Kidney Neoplasms; Lymphocyte Count; Male; Middle Aged; Neutrophils; Platelet Count; Prognosis; Pyrimidines; Sulfonamides; Sunitinib; Young Adult