Radiosensitizing effect of galunisertib, a TGF- ß receptor I inhibitor, on head and neck squamous cell carcinoma in vitro
Conclusion. Our results indicate a potential antineoplastic effect of galunisertib in HNSCC with intact TGF- ß signaling in combination with radiation. (Source: Investigational New Drugs)
Source: Investigational New Drugs - January 5, 2022 Category: Drugs & Pharmacology Source Type: research
Ad-VT enhances the sensitivity of chemotherapy-resistant lung adenocarcinoma cells to gemcitabine and paclitaxel in vitro and in vivo
Conclusions Thus, the combination of Ad-VT and chemotherapeutic drugs will be a promising strategy to overcome chemoresistance. (Source: Investigational New Drugs)
Source: Investigational New Drugs - January 4, 2022 Category: Drugs & Pharmacology Source Type: research
ERK inhibitor ASN007 effectively overcomes acquired resistance to EGFR inhibitor in non ‐small cell lung cancer
This study emphasizes the importance of targeting ERK signaling in maintaining the long-term benefits of EGFR TKIs by overcoming acquired resistance. (Source: Investigational New Drugs)
Source: Investigational New Drugs - January 1, 2022 Category: Drugs & Pharmacology Source Type: research
Phase II trial of brentuximab vedotin in relapsed/refractory germ cell tumors
Conclusion Brentuximab vedotin does not appear to have clinically meaningful single-agent activity in patients with refractory GCT. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 24, 2021 Category: Drugs & Pharmacology Source Type: research
Benzyl and phenethyl isothiocyanates as promising epigenetic drug compounds by modulating histone acetylation and methylation marks in malignant melanoma
We report that both isothiocyanates induced cytotoxicity and influenced acetylation and methylation status of specific lysine residues on histones H3 and H4 by modulating the expression of various histone acetyltransferases, deacetylases and methyltransferases in malignant melanoma cells. Our data highlight novel insights on the interaction of isothiocyanates with components of the histone regulatory machinery in order to exert their anti-cancer action in malignant melanoma. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 24, 2021 Category: Drugs & Pharmacology Source Type: research
Comparison of clinical features between immune-related sclerosing cholangitis and hepatitis
Conclusions IrSC and irHepatitis have different characteristics in the class of immune checkpoint inhibitor and onset pattern. Radiological examination for the diagnosis of irSC should be considered for patients with ≥ grade 2 ALP elevation resulting in a cholestatic pattern. (Registration number J2020-36, Date of registration June 3, 2020) (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 24, 2021 Category: Drugs & Pharmacology Source Type: research
Toxicity and antitumor activity of novel agents in elderly patients with cancer included in phase 1 studies
Conclusions This retrospective study found that elderly and younger populations had comparable antitumor activities and toxicity profiles. These results support including elderly patients with cancer in early-phase trials. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 24, 2021 Category: Drugs & Pharmacology Source Type: research
Real-world pharmacokinetics and pharmacodynamics of everolimus in metastatic breast cancer
Conclusions The suggested upper threshold for the therapeutic window of everolimus Ctrough was 17.3 ng/mL. Pharmacokinetically guided dosing may improve the efficacy and safety of everolimus for mBC, warranting further investigation in a larger study.Clinical trial registry: Not applicable. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 24, 2021 Category: Drugs & Pharmacology Source Type: research
Chemoprevention of pancreatic cancer by inhibition of glutathione-S transferase P1
In this study, chemopreventive effects of O-Hexadecyl- γ-glutamyl-S-benzyl-cysteinyl-D-phenyl glycine-Ethylester (HGBPE), which we previously synthesized to inhibit GSTP1 activity, was analyzed for its effect on the prevention of a rat pancreatic carcinogenesis model induced by 7,12-dimethyl-benzanthracene (DMBA). Rats administered with DMBA were group ed into five cohorts. In the treated group I, which was treated neither with HGBPE nor vehicle, sequential appearance of precancerous lesions, ductal complexes, and adenocarcinoma was confirmed as previously reported. We also confirmed in this group that mutations of KRAS a...
Source: Investigational New Drugs - October 24, 2021 Category: Drugs & Pharmacology Source Type: research
Phase I trial of copanlisib, a selective PI3K inhibitor, in combination with cetuximab in patients with recurrent and/or metastatic head and neck squamous cell carcinoma
Conclusion Copanlisib combined with cetuximab demonstrated unfavorable toxicity and limited efficacy in heavily pretreated recurrent and/or metastatic HNSCC patients.Trial registration NCT02822482, Date of registration: June 2016. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 24, 2021 Category: Drugs & Pharmacology Source Type: research
Rechallenge with previously administered epidermal growth factor receptor-tyrosine kinase inhibitors in EGFR-mutated non-small cell lung cancer with leptomeningeal metastasis
Conclusion Rechallenge of previously administered EGFR-TKIs may be a therapeutic option for LM development after EGFR-TKI treatment failure in patients with EGFR-mutated NSCLC, not only switching to previously unadministered EGFR-TKIs. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 24, 2021 Category: Drugs & Pharmacology Source Type: research
Gemcitabine, carboplatin and veliparib in multiple relapsed/refractory germ cell tumours: The GCT-SK-004 phase II trial
Conclusions This study failed to achieve its primary endpoint, and our data suggest limited efficacy of gemcitabine, carboplatin and veliparib for multiple relapsed/refractory GCTs. ClinicalTrials.gov Identifier: NCT02860819, registered August 9, 2016. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 24, 2021 Category: Drugs & Pharmacology Source Type: research
Comprehensive analysis of clinical prognosis and molecular immune characterization of tropomyosin 4 in pancreatic cancer
AbstractPancreatic cancer (PC) is one of the most lethal human solid malignancies with devastating prognosis, making biomarker detection considerably important. Immune infiltrates in microenvironment is associated with patients ’ survival in PC. The role of Tropomyosin 4 (TPM4) gene in PC has not been reported. Our study first identifies TPM4 expression and its potential biological functions in PC. The potential oncogenic roles of TPM4 was examined using the datasets of TCGA (The cancer genome atlas) and GEO (Gene expres sion omnibus). We investigated the clinical significance and prognostic value of TPM4 gene based on T...
Source: Investigational New Drugs - October 24, 2021 Category: Drugs & Pharmacology Source Type: research
A critical appraisal of Japan's new drug approval process: a case study of FLT3-ITD inhibitor quizartinib
AbstractIn the last two decades, simultaneous global development of novel drugs become more common by conducting multiregional clinical trials. However, regulatory authorities of different regions often make different decisions on the approvals of the same new drugs. We would like to discuss the appropriateness of Japanese regulatory approach through a case study of quizartinib, a novel anti-leukemia drug developed in Japan. The pivotal clinical trial “QuANTUM-R” conducted in 19 countries showed a modest increase in median overall survival with quizartinib than the conventional chemotherapy. However, because several cr...
Source: Investigational New Drugs - October 24, 2021 Category: Drugs & Pharmacology Source Type: research
Prognostic impact of pneumonitis after durvalumab therapy in patients with locally advanced non-small cell lung cancer
Conclusion. Grade 2 or higher pneumonitis after durvalumab was not a prognostic factor of PFS in LA-NSCLC patients received durvalumab. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 11, 2021 Category: Drugs & Pharmacology Source Type: research
