An overview of the clinical use of cabozantinib in the treatment of advanced non-clear-cell renal cell carcinoma (NCCRCC)

Patients diagnosed with non-clear renal cell carcinoma have often been excluded from clinical trials due to the shortage of treatments available, the low incidence of tumours with non-clear histology, and the corresponding diversity of intrinsic molecular features. This approach led to a knowledge gap in finding the optimal treatment for patients diagnosed with non-clear cell renal carcinoma. Cabozantinib, a potent multiple tyrosine kinase receptor inhibitor, has been recently investigated in patients with non-clear cell histologies of renal cell cancer. In this review, we have summarized available data on the use of cabozantinib in non-clear renal cell carcinoma.</p

Efficacy and Safety of Regorafenib With 2/1 Schedule for Patients ≥ 75 Years With Metastatic Colorectal Cancer (mCRC) After Failure of 2 Lines of Chemotherapy

Background: In the CORRECT (patients with metastatic COloRectal Cancer treated with REgorafenib or plaCebo after failure of standard Therapy) trial, regorafenib was proven to extend survival of patients with metastatic colorectal cancer (mCRC) that progressed after all available therapies. Grade 3 to 4 toxicity occurred in 54% of patients, and data on the activity and tolerability of regorafenib in elderly patients were scarce. The aim of this study was to evaluate the efficacy and safety of an alternative schedule, 2-week-on treatment and 1 week-off (2/1 schedule), of regorafenib for elderly patients with mCRC. Patients and Methods: Patients â\u89¥ 75 years with mCRC who progressed after oxaliplatin- and irinotecan-based chemotherapy received regorafenib on a 2/1 schedule. Potentially frail subjects were identified by G8 screening tool and excluded. The 2-month disease-control rate was the primary endpoint, and the secondary endpoints included safety, progression-free survival (PFS), overall survival (OS), and objective response rate. Results: Between February 2014 and May 2017, 23 patients with mCRC were recruited at our institution. No partial or complete responses were observed, and the stable disease and disease-control rate were 52.2%. The median PFS was 4.8 months (95% confidence interval, 3.8-6.3 months), and the median OS was 8.9 months (95% confidence interval, 6.9-10.6 months). Adverse events were uncommon, and the most frequent grade 3 toxicity adverse events were hand-foot skin reaction (9%) and fatigue (9%). Toxicity-related dose reductions and discontinuations occurred in 5 and 2 patients, respectively. Conclusion: Regorafenib administered with a modified 2/1 schedule to patients who were aged â\u89¥ 75 years and non-frail with treatment-refractory mCRC seems to be tolerable and achieve encouraging results in terms of PFS and OS

How the Potassium Channel Response of T Lymphocytes to the Tumor Microenvironment Shapes Antitumor Immunity

Competent antitumor immune cells are fundamental for tumor surveillance and combating active cancers. Once established, tumors generate a tumor microenvironment (TME) consisting of complex cellular and metabolic elements that serve to suppress the function of antitumor immune cells. T lymphocytes are key cellular elements of the TME. In this review, we explore the role of ion channels, particularly K+ channels, in mediating the suppressive effects of the TME on T cells. First, we will review the complex network of ion channels that mediate Ca2+ influx and control effector functions in T cells. Then, we will discuss how multiple features of the TME influence the antitumor capabilities of T cells via ion channels. We will focus on hypoxia, adenosine, and ionic imbalances in the TME, as well as overexpression of programmed cell death ligand 1 by cancer cells that either suppress K+ channels in T cells and/or benefit from regulating these channels’ activity, ultimately shaping the immune response. Finally, we will review some of the cancer treatment implications related to ion channels. A better understanding of the effects of the TME on ion channels in T lymphocytes could promote the development of more effective immunotherapies, especially for resistant solid malignancies

Pathological response and outcome after neoadjuvant chemotherapy with DOC (docetaxel, oxaliplatin, capecitabine) or EOF (epirubicin, oxaliplatin, 5-fluorouracil) for clinical T3-T4 non-metastatic gastric cancer

In this prospective observational study, we sought to compare the efficacy and safety of docetaxel&nbsp;+&nbsp;oxaliplatin&nbsp;+&nbsp;capecitabine (DOC) with epirubicin&nbsp;+&nbsp;oxaliplatin + 5-fluouracil (EOF) as neoadjuvant chemotherapy (NAC) for clinical T3 or T4 non-metastatic gastric cancer (GC) patients

Genetic parkinsonisms and cancer: A systematic review and meta-analysis

Genes associated with parkinsonism may also be implicated in carcinogenesis, but their interplay remains unclear. We systematically reviewed studies (PubMed 1967-2019) reporting gene variants associated with both parkinsonism and cancer. Somatic variants were examined in cancer samples, whereas germline variants were examined in cancer patients with both symptomatic and asymptomatic (carriers) genetic parkinsonisms. Pooled proportions were calculated with random-effects meta-analyses. Out of 9,967 eligible articles, 60 were included. Of the 28 genetic variants associated with parkinsonism, six were also associated with cancer. In cancer samples, SNCA was predominantly associated with gastrointestinal cancers, UCHL1 with breast cancer, and PRKN with head-and-neck cancers. In asymptomatic carriers, LRRK2 was predominantly associated with gastrointestinal and prostate cancers, PRKN with prostate and genitourinary tract cancers, GBA with sarcoma, and 22q11.2 deletion with leukemia. In symptomatic genetic parkinsonism, LRRK2 was associated with nonmelanoma skin cancers and breast cancers, and PRKN with head-and-neck cancers. Cancer was more often manifested in genetic parkinsonisms compared to asymptomatic carriers. These results suggest that intraindividual genetic contributions may modify the co-occurrence of cancer and neurodegeneration.Fil: Sturchio, Andrea. University of Cincinnati; Estados UnidosFil: Dwivedi, Alok K.. Texas Tech University Health Sciences Center El Paso; Estados UnidosFil: Vizcarra, Joaquin A.. University of Cincinnati; Estados Unidos. University of Emory; Estados UnidosFil: Chirra, Martina. Università degli Studi di Siena; ItaliaFil: Keeling, Elizabeth G.. University of Cincinnati; Estados UnidosFil: Mata, Ignacio F.. Cleveland Clinic Foundation; Estados UnidosFil: Kauffman, Marcelo Andres. Universidad de Buenos Aires. Facultad de Medicina. Centro Universitario de Neurología "Dr. José María Ramos Mejía".; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pandey, Manoj K.. University of Cincinnati; Estados UnidosFil: Roviello, Giandomenico. Università degli Studi di Firenze; ItaliaFil: Comi, Cristoforo. Università Degli Studi del Piemonte Orientale "amedeo Avogadro"; ItaliaFil: Versino, Maurizio. Università Degli Studi Dell'insubria; ItaliaFil: Marsili, Luca. University of Cincinnati; Estados UnidosFil: Espay, Alberto J.. University of Cincinnati; Estados Unido