Antitumor activity of the new tyrphostin briva against BRAFV600E-mutant colorectal carcinoma cells
SummaryBecause of a reduced sensitivity of BRAF-mutant colorectal cancers to BRAF inhibitor treatment when compared with BRAF-mutant melanoma, it is essential to develop efficient drugs to cope with this disease. The new 2-(4-bromophenyl)-3-arylacrylonitrile compound Briva was prepared in one step from commercially available starting compounds. Briva and two known thiophene analogs (Thio-Iva and Thio-Dam) were tested for their cytotoxic activity against various tumor cell lines including colorectal and breast cancer cells. The antitumor activities of the test compounds were assessed in vitro via the MTT assay, DAPI stainin...
Source: Investigational New Drugs - October 23, 2023 Category: Drugs & Pharmacology Source Type: research
Gastrointestinal signet ring cell malignancy: current advancement and future prospects
AbstractGlobally, gastrointestinal cancer is the most widespread neoplastic disease and the primary contributor to cancer-associated fatalities. Gastrointestinal signet ring cell carcinoma (SRCC) exhibits unique distinguishing features in several aspects when compared to adenocarcinomas (ACs). The scarcity of signet ring cell carcinoma has resulted in a heightened significance of related clinical and molecular investigations. However, a comprehensive and systematic review of the clinical, molecular, therapeutic, and research aspects of this disease is currently absent. This review provides an overview of the latest develop...
Source: Investigational New Drugs - October 21, 2023 Category: Drugs & Pharmacology Source Type: research
Optimal first-line treatment strategies of systemic therapy for unresectable gastrointestinal neuroendocrine tumors based on the opinions of Japanese experts.
SummaryThere are several options for systemic therapy of gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN), including somatostatin analogues (SSA), molecular-targeted agents, cytotoxic agents, and peptide receptor radionuclide therapy. However, the effectiveness of each agent varies according to the primary site. Although SSA and everolimus are key drugs used for systemic therapy of neuroendocrine tumors arising from the gastrointestinal tract (GI-NET), the optimal strategy for selecting among these modalities remains unexplored. Japanese experts on GI-NET discussed and determined optimal first-line treatment strat...
Source: Investigational New Drugs - October 19, 2023 Category: Drugs & Pharmacology Source Type: research
Therapeutic effectiveness of anlotinib combined with etoposide in extensive-stage small-cell lung cancer: a single-arm, phase II trial
ConclusionMaintenance anlotinib plus etoposide achieves promising PFS and OS in clinical ES-SCLC.Registration numberChiCTR1800019421. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 14, 2023 Category: Drugs & Pharmacology Source Type: research
Gefitinib, an effective treatment option for patients with pulmonary enteric adenocarcinoma harboring compound EGFR L858R and A871G mutation
We report a postoperative (T4N2M0 stage IIIb) PEAC patient with EGFR L858R + A871G combined mutation. Following surgery, the patient underwent treatment with the first-generation EGFR-TKI, gefitinib, and achieved an impressive 5-year progression-free survival (PFS). This suggests that gefitinib may serve as an effective treatment option for PEAC patients with EGFR L85 8R + A871G compound mutations. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 13, 2023 Category: Drugs & Pharmacology Source Type: research
Phase 1/1b open-label, dose-escalation study of fruquintinib in patients with advanced solid tumors in the United States
This study is registered atClinicaltrials.gov NCT03251378. (Source: Investigational New Drugs)
Source: Investigational New Drugs - October 5, 2023 Category: Drugs & Pharmacology Source Type: research
Clinical characterization, treatment, and outcome of nivolumab-induced bullous pemphigoid
ConclusionClinicians should closely monitor symptoms of BP in those receiving and discontinuing nivolumab, especially in older men. Early diagnosis and timely initiation of treatment may improve patient outcomes. (Source: Investigational New Drugs)
Source: Investigational New Drugs - September 29, 2023 Category: Drugs & Pharmacology Source Type: research
Safety and blood levels of daratumumab after switching from intravenous to subcutaneous administration in patients with multiple myeloma
In this study, we investigated the safety and blood levels of daratumumab after switching from IV to SC in patients with multiple myeloma (MM). Patients who switched from IV to SC of daratumumab between June 2021 and May 2022 at Kobe City Medical Center General Hospital were included in the study. Blood daratumumab levels were measured using liquid chromatography-tandem mass spectrometry. Safety after switching from IV to SC was evaluated for six months and graded according to the Common Terminology Criteria for Adverse Events, version 5.0. The median body weight of ten patients included in the analysis was 57.4 kg (rang...
Source: Investigational New Drugs - September 18, 2023 Category: Drugs & Pharmacology Source Type: research
Cancers, Vol. 15, Pages 4532: Dosimetry of a Novel 111Indium-Labeled Anti-P-Cadherin Monoclonal Antibody (FF-21101) in Non-Human Primates
lez
Osama Mawlawi
P-cadherin is associated with a wide range of tumor types, making it an attractive therapeutic target. FF-21101 is a human–mouse chimeric monoclonal antibody (mAb) directed against human P-cadherin, which has been radioconjugated with indium-111 (111In) utilizing a DOTA chelator. We investigated the biodistribution of FF-21101(111In) in cynomolgus macaques and extrapolated the results to estimate internal radiation doses of 111In- and yttrium-90 (90Y)-FF-21101 for targeted radioimmunotherapy in humans. Whole-body planar and SPECT imaging were performed at 0, 2, 24, 48, 72, 96, and 120 ...
Source: Cancers - September 13, 2023 Category: Cancer & Oncology Authors: Gregory Ravizzini William Erwin Louis De Palatis Lucia Martiniova Vivek Subbiah Vincenzo Paolillo Jennifer Mitchell Asa P. McCoy Jose Gonzalez Osama Mawlawi Tags: Article Source Type: research
A novel anticancer quinolone, (R)-WAC-224, has anti-leukemia activities against acute myeloid leukemia
This study evaluated the anti-leukemia potential ofR-WAC or racemic WAC-224 (WAC) in vitro and in vivo. R-WAC significantly inhibited the human AML cell line proliferation (MV4-11, HL60, and KG1a), which was comparable to daunorubicin and cytarabine, not affected by P-glycoprotein overexpression. WAC did neither increase serum troponin-T nor decrease the crypt numbers in the small intestine, indicating WAC was less toxic than doxorubicin.R-WAC monotherapy demonstrated prolonged survival in the AML mice model and inhibited tumor growth in the MV4-11 xenograft mice model. Moreover, the combination ofR-WAC and cytarabine demo...
Source: Investigational New Drugs - September 13, 2023 Category: Drugs & Pharmacology Source Type: research
A novel bivalent anti-c-MET/PD-1 bispecific antibody exhibits potent cytotoxicity against c-MET/PD-L1-positive colorectal cancer
In this study, in addition to the tumor intrinsic mechanism investigation with molecular biology assay in vitro, a humanized mouse model was used to evaluate antitumor activity of the BsAbin vivo. The BsAb could inhibit c-MET/PD-L1+ CRC cell migration and show strong antitumor activity against HCT116 tumors in mice, potentially by inducing the degradation of c-MET protein in a dose and time-dependent manner. The BsAb could suppress the phosphorylation of c-MET downstream proteins GRB2-associated-binding protein 1 (Gab1) and focal adhesion kinase (FAK). Considering the tumor extrinsic mechanism, the BsAb may promote phagocy...
Source: Investigational New Drugs - August 30, 2023 Category: Drugs & Pharmacology Source Type: research
Early on-treatment C-reactive protein and its kinetics predict survival and response in recurrent and/or metastatic head and neck cancer patients receiving first-line pembrolizumab
Conclusion: On-treatment CRP was identified as a prognostic biomarker for objective response and survival in R/M HNSCC patients receiving first-line pembrolizumab and could be easily incorporated into clinical practice as a widely avai lable and cost-effective biomarker. (Source: Investigational New Drugs)
Source: Investigational New Drugs - August 21, 2023 Category: Drugs & Pharmacology Source Type: research
The efficacy and safety of selective RET inhibitors in RET fusion-positive non-small cell lung cancer: a meta-analysis
Conclusions Selective RET inhibitors Pralsetinib and Selpercatinib have shown a good effect on RET fusion-positive NSCLC, with a low incidence of adverse events. (Source: Investigational New Drugs)
Source: Investigational New Drugs - August 21, 2023 Category: Drugs & Pharmacology Source Type: research
Clinical characteristics of liver injury induced by immune checkpoint inhibitors in patients with advanced biliary tract carcinoma
SummaryImmune-related liver injuries are closely associated with the liver ’s fundamental state. Patients with advanced biliary tract carcinoma (BTC) have poor liver function. We evaluated the clinical data of immune-related liver injury in patients with advanced BTC and gastric cancer (GC) during immune checkpoint inhibitor (ICI) treatment between February 2019 and July 2022 at Peking University First Hospital. Twenty-five patients with advanced BTC were identified. Fifteen patients (60%) experienced immune-related liver injury during ICI treatment. We also evaluated the clinical status of patients with GC in another gr...
Source: Investigational New Drugs - August 17, 2023 Category: Drugs & Pharmacology Source Type: research
Preclinical evaluation of the VEGF/Ang2 bispecific nanobody BI 836880 in nasopharyngeal carcinoma models
This study showed that BI 836880 has anti-proliferative, anti-angiogenic and possibly immunomodulatory effect in clinical models of NPC, therefore the dual targeting of VEGF and Ang2 signaling in NPC should be further investigated. (Source: Investigational New Drugs)
Source: Investigational New Drugs - August 12, 2023 Category: Drugs & Pharmacology Source Type: research
