Anti-cancer activity of ultra-short single-stranded polydeoxyribonucleotides
SummaryOne of the features that differentiate cancer cells is their increased proliferation rate, which creates an opportunity for general anti-tumor therapy directed against the elevated activity of replicative apparatus in tumor cells. Besides DNA synthesis, successful genome replication requires the reparation of the newly synthesized DNA. Malfunctions in reparation can cause fatal injuries in the genome and cell death. Recently we have found that the ultra-short single-stranded deoxyribose polynucleotides of random sequence (ssDNA) effectively inhibit the catalytic activity of DNA polymerase \(\beta\). This effect a...
Source: Investigational New Drugs - February 7, 2023 Category: Drugs & Pharmacology Source Type: research
A phase 1 open-label study to assess the relative bioavailability of TAK-931 tablets in reference to powder-in-capsule in patients with advanced solid tumors
SummaryIn this phase 1 open-label study, we assessed the relative bioavailability of a prototype tablet formulation of TAK-931, a cell division cycle 7 kinase inhibitor, in reference to the current powder-in-capsule (PIC) formulation in patients with advanced solid tumors for whom no effective standard treatment was available. Adult patients were randomized 1:1 in a crossover fashion to receive one dose of TAK-931 80 mg PIC on Day 1 and one dose of TAK-931 80 mg tablet on Day 3 (or the reverse sequence), followed by TAK-931 50 mg PIC once daily (QD) for 12 days starting from Day 5, before a 7-day rest period (Cycle 0)...
Source: Investigational New Drugs - February 1, 2023 Category: Drugs & Pharmacology Source Type: research
Novel pentacyclic derivatives and benzylidenes of the progesterone series cause anti-estrogenic and antiproliferative effects and induce apoptosis in breast cancer cells
AbstractThe promising antitumor effects of progesterone derivatives have been identified in many studies. However, the specific mechanism of action of this class of compounds has not been fully described. Therefore, in this study, we investigated the antiproliferative and (anti)estrogenic activities of novel pentacyclic derivatives and benzylidenes of the progesterone series. The antiproliferative effects of the compounds were evaluated on hormone-dependent MCF7 breast cancer cells using the MTT test. Estrogen receptor α (ERα) activity was assessed by a luciferase-based reporter assay. Immunoblotting was used to evaluat...
Source: Investigational New Drugs - January 25, 2023 Category: Drugs & Pharmacology Source Type: research
Viscosalactone B, a natural LSD1 inhibitor, inhibits proliferation in vitro and in vivo against prostate cancer cells
SummaryLysine-specific demethylase 1 (LSD1) has been a promising target to treat prostate cancer, and discovery of novel LSD1 inhibitors would have great clinical significance. In this work, viscosalactone B was first identified as a novel LSD1 inhibitor. Viscosalactone B isolated fromWithania Somnifera displayed antiproliferative activity against PC3, DU145, C42B, PC3/MDVR, DU145/MDVR, and C42B/MDVR cells with IC50 values of 1.17, 0.72, 3.86, 2.06, 0.96 and 1.15 μM, respectively. In comparison, it was a selective LSD1 inhibitor with an IC50 value of 970.27 nM and could induce a significant accumulation of LSD1 substr...
Source: Investigational New Drugs - January 24, 2023 Category: Drugs & Pharmacology Source Type: research
Population Pharmacokinetics, Pharmacogenomics, and Adverse Events of Osimertinib and its Two Active Metabolites, AZ5104 and AZ7550, in Japanese Patients with Advanced Non-small Cell Lung Cancer: a Prospective Observational Study
Conclusion: Higher exposures to osimertinib, AZ5104, and AZ7550 and polymorphisms inEGFR,ABCG2, andABCB1 were related to higher severity of AEs; therefore, monitoring these may be beneficial for osimertinib AE management. (Source: Investigational New Drugs)
Source: Investigational New Drugs - January 13, 2023 Category: Drugs & Pharmacology Source Type: research
Combination carboplatin and nab-paclitaxel as a first-line treatment for advanced thymic carcinoma
SummaryThymic carcinoma is a very rare neoplasm for which no optimal chemotherapeutic regimen has been established to date. Hence, we performed this study to investigate the efficacy and safety of carboplatin plus nanoparticle albumin-bound (nab)-paclitaxel as a first-line regimen for patients with advanced thymic carcinoma. We conducted this multi-institutional retrospective cohort study of patients with advanced thymic carcinoma who had received carboplatin plusnab-paclitaxel as a first-line chemotherapy between August 2013 and December 2021. Twelve patients were included in this study and were subjected to efficacy and ...
Source: Investigational New Drugs - January 12, 2023 Category: Drugs & Pharmacology Source Type: research
A phase 1 study of intravenous mitazalimab, a CD40 agonistic monoclonal antibody, in patients with advanced solid tumors
SummaryMitazalimab is an agonistic human monoclonal antibody targeting CD40, a target for anti-tumor immunotherapy. This phase 1, dose-escalation study evaluated the safety, dose-limiting toxicities (DLTs), pharmacokinetic and pharmacodynamic profile of mitazalimab. Adults with advanced solid malignancies received mitazalimab intravenously once every-2-weeks. Dose-escalation was pursued with and without pre-infusion corticosteroids for mitigation of infusion-related reactions (IRRs).
In all, 95 patients were enrolled in 7 cohorts (n = 50, 75–2000 µg/kg) with corticosteroids and in 5 cohorts (n = 45, 75–12...
Source: Investigational New Drugs - December 20, 2022 Category: Drugs & Pharmacology Source Type: research
DGG-300273, a novel WNT/ β-catenin inhibitor, induces apoptotic cell death by activating ROS-BIM signaling in a Wnt-dependent manner in colon cancer cells
SummaryDysregulated Wnt signaling is associated with malignant oncogenic transformation, especially in colon cancer. Recently, numerous drugs have been developed based on tumorigenesis biomarkers, thus having high potential as drug targets. Likewise, WNT/ β-catenin pathway members are attractive therapeutic targets for colon cancer and are currently in various stages of development. However, although inhibitors of proteins regulating the WNT/β-catenin signaling pathway have been extensively studied, they have yet to be clinically approved, and the underlying molecular mechanism(s) of their anticancer effects remain poorl...
Source: Investigational New Drugs - December 20, 2022 Category: Drugs & Pharmacology Source Type: research
Corrections to: Combination of TACE and Lenvatinib as a promising option for downstaging to surgery of initially unresectable intrahepatic cholangiocarcinoma
(Source: Investigational New Drugs)
Source: Investigational New Drugs - December 13, 2022 Category: Drugs & Pharmacology Source Type: research
Neoadjuvant toripalimab plus platinum-paclitaxel chemotherapy in stage II-III non-small cell lung cancer: a single-center, single-arm, phase I study in China
ConclusionNeoadjuvant toripalimab plus platinum-paclitaxel chemotherapy was tolerable and induced a pathological complete response in 55% of resectable NSCLC patients. (Source: Investigational New Drugs)
Source: Investigational New Drugs - December 12, 2022 Category: Drugs & Pharmacology Source Type: research
Ocular toxicity of investigational anti-cancer drugs in early phase clinical trials
This study reported the risks and timing of the ons et of a variety of ocular toxicities of anti-cancer drugs, which were fundamentally controllable. (Trial registration number. Retrospectively registered) (Source: Investigational New Drugs)
Source: Investigational New Drugs - December 5, 2022 Category: Drugs & Pharmacology Source Type: research
A prospective multicenter phase II study of FOLFIRINOX as a first-line treatment for patients with advanced and recurrent biliary tract cancer
This study defined primary endpoint might be met when the lower limit value of 80% confidence interval [CI] of the median PFS ≥ 6.0 months.
Between June 2016 and March 2020, 35 BTC patients (21 intrahepatic, 10 extrahepatic, 2 gallbladder, 2 ampulla) including 26 unresectable and 9 recurrent disease were enrolled. After a median follow-up of 13.9 months, the median PFS and OS were 7.4 (80% CI, 5.5–7.5) and 14.7 (80% CI, 11.8–15.7) months, respectively. Complete response was achieved in 1 (2.9%) and partial response in 10 (28.6%), giving an objective response rate of 31.4% and disease control rate of 74.3%. ...
Source: Investigational New Drugs - December 2, 2022 Category: Drugs & Pharmacology Source Type: research
BMP2 as a promising anticancer approach: functions and molecular mechanisms
SummaryBone morphogenetic protein 2 (BMP2), a pluripotent factor, is a member of the transforming growth factor-beta (TGF- β) superfamily and is implicated in embryonic development and postnatal homeostasis in tissues and organs. Experimental research in the contexts of physiology and pathology has indicated that BMP2 can induce macrophages to differentiate into osteoclasts and accelerate the osteolytic mechanism, aggr avating cancer cell bone metastasis. Emerging studies have stressed the potent regulatory effect of BMP2 in cancer cell differentiation, proliferation, survival, and apoptosis. Complicated signaling network...
Source: Investigational New Drugs - November 12, 2022 Category: Drugs & Pharmacology Source Type: research
Effects of CYP3A4/5 and ABC transporter polymorphisms on osimertinib plasma concentrations in Japanese patients with non-small cell lung cancer
SummaryThe effects of polymorphisms inCYP3A4 (20230G > A),CYP3A5 (6986A > G),ABCB1 (1236C > T, 2677G > T/A, 3435C > T),ABCG2 (421C > A), andABCC2 (-24C > T) on the area under the concentration–time curve (AUC) of osimertinib in 23 patients with non-small cell lung cancer were investigated. Blood sampling was performed just prior to and at 1, 2, 4, 6, 8, 12, and 24 h after osimertinib administration at the steady-state on day 15 after beginning therapy. The osimertinib AUC0-24 was significantly correlated with age (P = 0.038), serum albumin (P = 0.002),...
Source: Investigational New Drugs - November 12, 2022 Category: Drugs & Pharmacology Source Type: research
Combination of ruxolitinib with ABT-737 exhibits synergistic effects in cells carrying concurrent JAK2V617F and ASXL1 mutations
In conclusion, we provide preclinical evidence showing that the combination of ruxolitinib and ABT-737 is a promising therapeutic strategy for MPN patients with concurrentJAK2V617F andASXL1 mutations. (Source: Investigational New Drugs)
Source: Investigational New Drugs - November 12, 2022 Category: Drugs & Pharmacology Source Type: research
