A novel methylated analogue of L-Mimosine exerts its therapeutic potency through ROS production and ceramide-induced apoptosis in malignant melanoma
SummaryMelanoma is an aggressive and highly metastatic type of skin cancer where the design of new therapies is of utmost importance for the clinical management of the disease. Thus, we have aimed to investigate the mode of action by which a novel methylated analogue ofL-Mimosine (e.g.,L-SK-4) exerts its therapeutic potency in an in vitro model of malignant melanoma. Cytotoxicity was assessed by the Alamar Blue assay, oxidative stress by commercially available kits, ROS generation, caspase 3/7 activation and mitochondrial membrane depolarisation by flow cytometry, expression of apoptosis-related proteins by western immunob...
Source: Investigational New Drugs - July 14, 2021 Category: Drugs & Pharmacology Source Type: research

System Xc −: a key regulatory target of ferroptosis in cancer
SummaryFerroptosis is a type of oxidative stress-dependent regulated necrosis characterized by excessive lipid peroxide accumulation. This novel cell death modality has been implicated in preventing cancer progression. Cancer cells tend to modulate their redox state to prevent excessive peroxidation, eventually facilitating tumor growth. System Xc− (a cystine/glutamate antiporter system) is a promising target in cancer cells for ferroptosis induction. The overexpression of system Xc−, especially its core subunit xCT, has been reported in several tumors, and these high expression levels were closely related to c...
Source: Investigational New Drugs - July 14, 2021 Category: Drugs & Pharmacology Source Type: research

Significant benefit of everolimus in a patient with urothelial bladder cancer harboring a rare M1043I mutation of PIK3CA
SummaryUrothelial bladder cancer (UBC) is a common malignancy with considerable mortality worldwide. However, the treatment options of UBC are mainly chemotherapy and immunotherapy, as few targeted agents have demonstrated efficacy against UBC. In recent studies, everolimus has exhibited antitumor activity in patients harboring aberrations in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/ mammalian target of rapamycin (mTOR) pathway in multiple tumor types. Herein, we report the case of a patient with metastatic UBC harboring a rare M1043I mutation ofPIK3CA which was detected using DNA-based next-generati...
Source: Investigational New Drugs - July 14, 2021 Category: Drugs & Pharmacology Source Type: research

The biological  function of IGF2BPs and their role in tumorigenesis
SummaryThe insulin-like growth factor-2 mRNA-binding proteins (IGF2BPs) pertain to a highly conservative RNA-binding family that works as a post-transcriptional fine-tuner for target transcripts. Emerging  evidence suggests that IGF2BPs regulate RNA processing and metabolism, including stability, translation, and localization, and are involved in various cellular functions and pathophysiologies. In this review, we summarize the roles and molecular mechanisms of IGF2BPs in cancer development and prog ression. We mainly discuss the functional relevance of IGF2BPs in embryo development, neurogenesis, metabolism, RNA proc...
Source: Investigational New Drugs - July 12, 2021 Category: Drugs & Pharmacology Source Type: research

Phase 1 dose escalation study of seribantumab (MM-121), an anti-HER3 monoclonal antibody, in patients with advanced solid tumors
Conclusions Seribantumab monotherapy was well tolerated across all dose levels. Safety and PK data from this study support further seribantumab investigations in genomically defined populations.Clinical trial registration  NCT00734305. August 12, 2008. (Source: Investigational New Drugs)
Source: Investigational New Drugs - July 11, 2021 Category: Drugs & Pharmacology Source Type: research

Serine hydroxymethyltransferase 2: a novel target for human cancer therapy
SummarySerine and glycine are the primary sources of one-carbon units that are vital for cell proliferation. Their abnormal metabolism is known to be associated with cancer progression. As the key enzyme of serine metabolism, Serine Hydroxymethyltransferase 2 (SHMT2) has been a research hotspot in recent years. SHMT2 is a PLP-dependent tetrameric enzyme that catalyzes the reversible transition from serine to glycine, thus promoting the production of one-carbon units that are indispensable for cell growth and regulation of the redox and epigenetic states of cells. Under a hypoxic environment, SHMT2 can be upregulated and co...
Source: Investigational New Drugs - July 3, 2021 Category: Drugs & Pharmacology Source Type: research

Phase 1b study of ramucirumab in combination with erlotinib or osimertinib for untreated EGFR-mutated non –small cell lung cancer patients with asymptomatic brain metastases
Conclusion: Ramucirumab in combination with erlotinib or osimertinib showed safety forEGFR-mutated NSCLC with brain metastases. (Source: Investigational New Drugs)
Source: Investigational New Drugs - July 2, 2021 Category: Drugs & Pharmacology Source Type: research

Network pharmacology of triptolide in cancer cells: implications for transcription factor binding
Conclusion  Triptolide showed promising inhibitory effect toward NF- κB, making it a potential candidate for targeting NF-κB. (Source: Investigational New Drugs)
Source: Investigational New Drugs - July 2, 2021 Category: Drugs & Pharmacology Source Type: research

Development and validation of a ferroptosis-related prognostic model in pancreatic cancer
SummaryBackground: The purpose of this study was to identify ferroptosis-related genes (FRGs) associated with the prognosis of pancreatic cancer and to construct a prognostic model based on FRGs.Methods: Based on pancreatic cancer data obtained from The Cancer Genome Atlas database, we established a prognostic model from 232 FRGs. A nomogram was constructed by combining the prognostic model and clinicopathological features. Gene Expression Omnibus datasets and tissue samples obtained from our center were utilized to validate the model. The relationship between risk score and immune cell infiltration was explored by CIBERSO...
Source: Investigational New Drugs - June 30, 2021 Category: Drugs & Pharmacology Source Type: research

Phase I study of daily and weekly regimens of the orally administered MDM2 antagonist idasanutlin in patients with advanced tumors
Conclusions Idasanutlin demonstrated dose- and schedule-dependent p53 activation with durable disease stabilization in some patients. Based on these findings, the QD × 5 schedule was selected for further development.Trial registrationNCT01462175 (ClinicalTrials.gov), October 31, 2011. (Source: Investigational New Drugs)
Source: Investigational New Drugs - June 28, 2021 Category: Drugs & Pharmacology Source Type: research

Combination therapy with pazopanib and tivantinib modulates VEGF and c-MET levels in refractory advanced solid tumors
SummaryThe vascular endothelial growth factor (VEGF)/VEGFR and hepatocyte growth factor (HGF)/c-MET signaling pathways act synergistically to promote angiogenesis. Studies indicate VEGF inhibition leads to increased levels of phosphorylated c-MET, bypassing VEGF-mediated angiogenesis and leading to chemoresistance. We conducted a phase 1 clinical trial with 32 patients with refractory solid tumors  to evaluate the safety, pharmacokinetics, and pharmacodynamics of combinations of VEGF-targeting pazopanib and the putative c-MET inhibitor ARQ197 (tivantinib) at 5 dose levels (DLs). Patients either took pazopanib and tiva...
Source: Investigational New Drugs - June 28, 2021 Category: Drugs & Pharmacology Source Type: research

Safety, pharmacokinetics, and preliminary efficacy of the PARP inhibitor talazoparib in Japanese patients with advanced solid tumors: phase 1 study
Conclusions: Single-agent talazoparib was well tolerated and had preliminary antitumor activity in Japanese patients with advanced solid tumors.ClinicalTrials.gov identifier: NCT03343054 (November 17, 2017). (Source: Investigational New Drugs)
Source: Investigational New Drugs - June 23, 2021 Category: Drugs & Pharmacology Source Type: research

Apatinib with doxorubicin and ifosfamide as neoadjuvant therapy for high-risk soft tissue sarcomas: a retrospective cohort study
ConclusionApatinib plus doxorubicin and ifosfamide regimen is safe and effective as neoadjuvant therapy for patients with STS. However, the significantly improved preoperative ORR observed after neoadjuvant therapy did not translate into a significantly improved R0 rate and 2-year DFS. Prospective, well-powered studies are warranted to determine the long-term efficacy and optimal application of these protocols. (Source: Investigational New Drugs)
Source: Investigational New Drugs - June 22, 2021 Category: Drugs & Pharmacology Source Type: research

Efficacy and safety of TAS-115, a novel oral multi-kinase inhibitor, in osteosarcoma: an expansion cohort of a phase I study
Conclusion the safety and tolerability of TAS-115 and long-term disease stability for patients with unresectable or recurrent osteosarcoma were confirmed in this study, suggesting that TAS-115 is a promising novel therapy for advanced osteosarcoma patients. Trial registration number: JapicCTI-132333 (registered on November 8, 2013). (Source: Investigational New Drugs)
Source: Investigational New Drugs - June 12, 2021 Category: Drugs & Pharmacology Source Type: research

Phase 1a study of the CDK4/6 inhibitor, FCN-437c, in Chinese patients with HR  + /HER2- advanced breast cancer
Conclusions  These results established an acceptable safety profile for FCN-437c in patients with advanced BC, and there were no unexpected signals relative to other CDK4/6 inhibitors. (NCT04488107; July 13, 2020) (Source: Investigational New Drugs)
Source: Investigational New Drugs - June 9, 2021 Category: Drugs & Pharmacology Source Type: research

4Ei-10 interdiction of oncogenic cap-mediated translation as therapy for non-small cell lung cancer
SummaryIn order to suppress 5 ′ cap-mediated translation a highly available inhibitor of the interaction between the 5’ mRNA cap and the eIF4E complex has been developed. 4Ei-10 is a member of the class of ProTide compounds and has elevated membrane permeability and is a strong active chemical antagonist for eIF4E. Once take n up by cells it is converted by anchimeric activation of the lipophilic 2-(methylthio) ethyl protecting group and after that Hint1 P-N bond cleavage toN7-(p-chlorophenoxyethyl) guanosine 5 ′-monophosphate (7-Cl-Ph-Ethyl-GMP). Using this powerful interaction, it has been demonstrated ...
Source: Investigational New Drugs - April 25, 2021 Category: Drugs & Pharmacology Source Type: research

Signal transducer and activator of transcription 3 inhibition alleviates resistance to BRAF inhibition in anaplastic thyroid cancer
In this study, we aimed to study on resistant mechanisms to B-Raf proto-oncogene serine/threonine kinase (BRAF) inhibitor and identify effective combinational therapy for ATC patients. TC cells were treated with Vemurafenib and cell apoptosis and viability were analyzed by flow cytometry and MTT assay. Monolayer and sphere cells were isolated from ATC cells to detect the mRNA level of stem cell markers and differentiation markers by RT-PCR. Phosphor-STAT3 level in sphere and monolayer cells was tested by Western blotting. The xenotransplantation animal model has established to analyze the anti-tumor effect of Vemurafenib a...
Source: Investigational New Drugs - April 25, 2021 Category: Drugs & Pharmacology Source Type: research

Generation of fully human anti-GPC3 antibodies with high-affinity recognition of GPC3 positive tumors
SummaryThe acceleration of therapeutic antibody development has been motivated by the benefit to and their demand for human health. In particular, humanized transgenic antibody discovery platforms, combined with immunization, hybridoma fusion and/or single cell DNA sequencing are the most reliable and rapid methods for mining the human monoclonal antibodies. Human GPC3 protein is an oncofetal antigen, and it is highly expressed in most hepatocellular carcinomas and some types of squamous cell carcinomas. Currently, no fully human anti-GPC3 therapeutic antibodies have been reported and evaluated in extensive tumor tissues. ...
Source: Investigational New Drugs - April 25, 2021 Category: Drugs & Pharmacology Source Type: research

A phase II clinical study on the efficacy and predictive biomarker of pegylated recombinant arginase on hepatocellular carcinoma
Conclusions: PEG-BCT-100 in chemo na ïve post-sorafenib HCC is well tolerated with moderate DCR. ASS-negative confers OS advantage over ASS-positive HCC. ASS-negativity is a potential biomarker for OS in HCC and possibly for other ASS-negative arginine auxotrophic cancers. Trial registration number: NCT01092091. Date of registration: March 23, 2010. (Source: Investigational New Drugs)
Source: Investigational New Drugs - April 15, 2021 Category: Drugs & Pharmacology Source Type: research

A phase 1a/1b trial of CSF-1R inhibitor LY3022855 in combination with durvalumab or tremelimumab in patients with advanced solid tumors
Conclusions LY3022855 combined with durvalumab or tremelimumab in patients with advanced NSCLC or OC had limited clinical activity, was well tolerated. The RP2D was LY3022855 100  mg QW with durvalumab 750 mg Q2W.ClinicalTrials.gov ID:NCT02718911 (Registration Date: May 3, 2011). (Source: Investigational New Drugs)
Source: Investigational New Drugs - April 14, 2021 Category: Drugs & Pharmacology Source Type: research

Successful treatment of an adult patient with diffuse midline glioma employing olaparib combined with bevacizumab
This report provides a promising treatment option for patients with DMG. (Source: Investigational New Drugs)
Source: Investigational New Drugs - April 13, 2021 Category: Drugs & Pharmacology Source Type: research

Efficacy and safety of S-1 following gemcitabine with cisplatin for advanced biliary tract cancer
Conclusions The efficacy and safety of S-1 following GC were almost the same as those of S-1 following GEM monotherapy for unresectable or recurrent BTC. (Source: Investigational New Drugs)
Source: Investigational New Drugs - April 9, 2021 Category: Drugs & Pharmacology Source Type: research

Icotinib, an effective treatment option for patients with lung adenocarcinoma harboring compound EGFR L858R and A871G mutation
SummaryCompound epidermal growth factor receptor (EGFR) mutations are defined as double or multiple independent mutations of theEGFR tyrosine kinase domain (TKD), in which anEGFR-tyrosine kinase inhibitor (TKI)-sensitizing mutation is identified together with a mutation of unclarified clinical significance. Lung adenocarcinoma with compoundEGFR mutation shows poor clinical response toEGFR-TKIs. Kobayashi et al. reported a non-small-cell lung cancer (NSCLC) patient whose tumor hadEGFR exon21 L858R/A871G mutation presented rapid disease progression to erlotinib. However, in this case, we present anEGFR exon21 L858R/A871G mut...
Source: Investigational New Drugs - April 9, 2021 Category: Drugs & Pharmacology Source Type: research

Pharmacokinetics of the oral multikinase inhibitor regorafenib and its association with real ‐world treatment outcomes
Conclusions  Dose titration of regorafenib to achieve drug-related Ctrough levels between 2.9 and 4.3  µg/mL in Cycle 1 may improve efficacy and safety, warranting further investigation in a larger patient population.Clinical trial registry: Not applicable. (Source: Investigational New Drugs)
Source: Investigational New Drugs - April 8, 2021 Category: Drugs & Pharmacology Source Type: research

First-in-human evaluation of the novel mitochondrial complex I inhibitor ASP4132 for treatment of cancer
Conclusions ASP4132 showed limited clinical activity, and DLTs prohibited dose escalation. Further research is required to determine if DLTs will limit clinical activity of other mitochondrial complex I inhibitors.Clinical Trial ID (clinicaltrials.gov): NCT02383368, March 9, 2015. (Source: Investigational New Drugs)
Source: Investigational New Drugs - April 8, 2021 Category: Drugs & Pharmacology Source Type: research

A phase 1 dose-escalation and dose-expansion study to assess the safety and efficacy of CKD-516, a novel vascular disrupting agent, in combination with Irinotecan in patients with previously treated metastatic colorectal cancer
Conclusion This phase 1 study showed that the combination of oral CKD-516 and irinotecan is safe and tolerable in metastatic, treatment-refractory colorectal patients and showed favorable efficacy outcomes. Further studies to confirm these preliminary findings are warranted.Trial registration number NCT03076957 (Registered at March 10, 2017). (Source: Investigational New Drugs)
Source: Investigational New Drugs - April 7, 2021 Category: Drugs & Pharmacology Source Type: research

FGFR leads to sustained activation of STAT3 to mediate resistance to EGFR-TKIs treatment
SummaryEpidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have led to great advances in the treatment of non-small cell lung cancer (NSCLC), but the emergence of drug resistance severely limits their clinical use. Thus, elucidation of the mechanism underlying resistance to EGFR-TKIs is of great importance. In our study, sustained activation of STAT3 was confirmed to be involved in resistance to EGFR-TKIs, and this resistance occurred regardless of exposure time, EGFR-TKIs type, and even cancer cell type. Mechanistically, the sustained activation of STAT3 was not related to gp130/JAK signalling pathway ...
Source: Investigational New Drugs - April 7, 2021 Category: Drugs & Pharmacology Source Type: research

A phase 1 study of crenigacestat (LY3039478), the Notch inhibitor, in Japanese patients with advanced solid tumors
Conclusions Crenigacestat was tolerated in Japanese patients but with limited clinical activity. The recommended crenigacestat dose in Japanese patients is 50  mg TIW.Trial registration: NCT02836600 (ClinicalTrials.gov) registered on July 19, 2016. (Source: Investigational New Drugs)
Source: Investigational New Drugs - March 16, 2021 Category: Drugs & Pharmacology Source Type: research

Notoginsenoside R1 counteracts mesenchymal stem cell-evoked oncogenesis and doxorubicin resistance in osteosarcoma cells by blocking IL-6 secretion-induced JAK2/STAT3 signaling
SummaryTumor microenvironment is a critical participant in the initiation, progression and drug resistance of carcinomas, including osteosarcoma. Notoginsenoside R1 (NGR1) is a proverbial active ingredient of the traditional Chinese medicinePanax notoginseng (PN) and possess undeniable roles in several cancers. Nevertheless, its function in osteosarcoma and tumor microenvironment remains elusive. In the current study, exposure to NGR1 dose-dependently inhibited osteosarcoma cell viability and migration, and induced apoptosis. Furthermore, osteosarcoma cells that were incubated with conditioned medium (CM) from bone marrow ...
Source: Investigational New Drugs - March 16, 2021 Category: Drugs & Pharmacology Source Type: research

Discovery of oxyepiberberine as a novel tubulin polymerization inhibitor and an anti-colon cancer agent against LS-1034 cells
Conclusion Oxyepiberberine was found as a novel tubulin polymerization inhibitor, and it could be a promising agent to treat colon cancer. (Source: Investigational New Drugs)
Source: Investigational New Drugs - March 16, 2021 Category: Drugs & Pharmacology Source Type: research

Switch maintenance therapy with anlotinib after chemotherapy in unresectable or metastatic soft tissue sarcoma: a single-center retrospective study
Conclusion Our results indicate that switch maintenance therapy with anlotinib is a promising strategy for the treatment of patients with unresectable or metastatic STS who have benefited from chemotherapy. Toxicities were manageable. Prospective clinical trials are needed to confirm this finding. (Source: Investigational New Drugs)
Source: Investigational New Drugs - March 16, 2021 Category: Drugs & Pharmacology Source Type: research

rAj-Tspin, a novel recombinant peptide from Apostichopus japonicus , suppresses the proliferation, migration, and invasion of BEL-7402 cells via a mechanism associated with the ITGB1-FAK-AKT pathway
Conclusion rAj-Tspin exerts an antitumor effect through the ITGB1-FAK-Akt signaling pathway and exhibits low toxicity at an effective dose. (Source: Investigational New Drugs)
Source: Investigational New Drugs - March 16, 2021 Category: Drugs & Pharmacology Source Type: research

A retrospective comparative study of S-IROX and modified FOLFIRINOX for patients with advanced pancreatic cancer refractory to gemcitabine plus nab-paclitaxel
Conclusions: S-IROX and mFFX were similarly tolerable and effective as a second-line chemotherapy in patients with PC refractory to gemcitabine plus nab-paclitaxel. (Source: Investigational New Drugs)
Source: Investigational New Drugs - March 16, 2021 Category: Drugs & Pharmacology Source Type: research

Phase II study of amrubicin plus erlotinib in previously treated, advanced non-small cell lung cancer with wild-type epidermal growth factor receptor (TORG1320)
SummaryBackground Amrubicin (AMR) is a completely synthetic 9-aminoanthracycline and clinically active against non-small cell lung cancer (NSCLC). We conducted a phase I study of AMR and erlotinib (ERL) combination therapy in previously treated patients with advanced NSCLC and have already reported the safety and effectiveness.Methods We conducted a multi-center, single-arm phase II trial to evaluate the efficacy of AMR and ERL combination therapy in patients with previously treated, advanced NSCLC harboring wild-type EGFR, PS 0 –1 and 
Source: Investigational New Drugs - March 16, 2021 Category: Drugs & Pharmacology Source Type: research

Nab-paclitaxel-based regimens with docetaxel-based regimens as neoadjuvant treatment for early breast cancer
Conclusions This study presented antitumor activity of nPBC and DBC in patients with early breast cancer receiving neoadjuvant treatment in a real-world setting. Further prospective research is warranted to confirm the results and to develop biomarkers for better patient selection. (Source: Investigational New Drugs)
Source: Investigational New Drugs - March 16, 2021 Category: Drugs & Pharmacology Source Type: research

Phase I study assessing the mass balance, pharmacokinetics, and excretion of [ 14 C]-pevonedistat, a NEDD8-activating enzyme inhibitor in patients with advanced solid tumors
SummaryPevonedistat (TAK-924/MLN4924) is an investigational small-molecule inhibitor of the NEDD8-activating enzyme that has demonstrated preclinical and clinical activity across solid tumors and hematological malignancies. Here we report the results of a phase I trial characterizing the mass balance, pharmacokinetics, and clearance pathways of [14C]-pevonedistat in patients with advanced solid tumors (NCT03057366). In part A (n = 8), patients received a single 1-h intravenous infusion of [14C]-pevonedistat 25  mg/m2. In part B (n = 7), patients received pevonedistat 25 or 20 mg/m2 on ...
Source: Investigational New Drugs - March 16, 2021 Category: Drugs & Pharmacology Source Type: research

Identification and characterization of deschloro-chlorothricin obtained from a large natural product library targeting aurora A kinase in multiple myeloma
SummaryMultiple myeloma (MM) is a devastating disease with low survival rates worldwide. The mean lifetime of patients may be extendable with new drug alternatives. Aurora A kinase (AURKA) is crucial in oncogenesis, because its overexpression or amplification may incline the development of various types of cancer, including MM. Therefore, inhibitors of AURKA are innovative and promising targets. Natural compounds always represented a valuable resource for anticancer drug development. In the present study, based on virtual drug screening of more than 48,000 natural compounds, the antibiotic deschloro-chlorotricin (DCCT) has...
Source: Investigational New Drugs - March 16, 2021 Category: Drugs & Pharmacology Source Type: research

Retrospective analysis of osimertinib re-challenge after osimertinib-induced interstitial lung disease in patients with EGFR-mutant non-small cell lung carcinoma
SummaryOsimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has exhibited efficacy in patients with EGFR-mutant non-small cell lung cancer (NSCLC). Interstitial lung disease (ILD) is a fatal adverse event of osimertinib treatment, and it requires treatment discontinuation. There are few reports regarding the safety and efficacy of osimertinib re-challenge in patients who experienced osimertinib-induced ILD. This retrospective study assessed this treatment option. We retrospectively collected data for patients treated with osimertinib who developed ILD at Shizuoka Ca...
Source: Investigational New Drugs - March 16, 2021 Category: Drugs & Pharmacology Source Type: research

A phase II study of Mirvetuximab Soravtansine in triple-negative breast cancer
SummaryFolate receptor alpha (FR α) has been reported to be expressed in up to 80% of triple-negative breast cancers (TNBC) with limited expression in normal tissues, making it a promising therapeutic target. Mirvetuximab soravtansine (mirvetuximab-s) is an antibody drug conjugate which has shown promise in the treatment of FRα-p ositive solid tumors in early phase clinical trials. Herein, are the results of the first prospective phase II trial evaluating mirvetuximab-s in metastatic TNBC. Patients with advanced, FRα-positive TNBC were enrolled on this study. Mirvetuximab-s was administered at a dose of 6...
Source: Investigational New Drugs - March 16, 2021 Category: Drugs & Pharmacology Source Type: research

Comment on: an orally antitumor chalcone hybrid inhibited HepG2 cells growth and migration as the tubulin binding agent
SummaryRecently we read a paper in Investigational New Drugs “An orally antitumor chalcone hybrid inhibited HepG2 cells growth and migration as the tubulin binding agent”. Chalcone hybrid 9, a novel chalcone derivative, may be a promising agent for the treatment of hepatocellular carcinoma. However, there are some problems in this paper that are worthy of comment. Human hepatocellular carcinoma HepG2 cells from Shanghai Research Science Limited Company could generate xenograft in nude mice and chalcone hybrid 9 suppressed the growth of HepG2 tumor. However, according to the description of cell bank of Chinese A...
Source: Investigational New Drugs - March 16, 2021 Category: Drugs & Pharmacology Source Type: research

Phase I first-in-human study of HLX07, a novel and improved recombinant anti-EGFR humanized monoclonal antibody, in patients with advanced solid cancers
Conclusion HLX07 was well tolerated (at dose levels up to 800  mg/week) and promising in patients with advanced solid cancers.Clinical Trial Registration: The study was registered atClinicalTrials.gov: NCT02648490 (Jan 7, 2016). (Source: Investigational New Drugs)
Source: Investigational New Drugs - March 13, 2021 Category: Drugs & Pharmacology Source Type: research

Discovery of MTR-106 as a highly potent G-quadruplex stabilizer for treating BRCA-deficient cancers
SummaryG-quadruplexes (G4s) are DNA or RNA structures formed by guanine-rich repeating sequences. Recently, G4s have become a highly attractive therapeutic target for BRCA-deficient cancers. Here, we show that a substituted quinolone amide compound, MTR-106, stabilizes DNA G-quadruplexesin vitro. MTR-106 displayed significant antiproliferative activity in homologous recombination repair (HR)-deficient and PARP inhibitor (PARPi)-resistant cancer cells. Moreover, MTR-106 increased DNA damage and promoted cell cycle arrest and apoptosis to inhibit cell growth. Importantly, its oral andi.v. administration significantly impaire...
Source: Investigational New Drugs - March 12, 2021 Category: Drugs & Pharmacology Source Type: research

Real-world prospective analysis of treatment patterns in durvalumab maintenance after chemoradiotherapy in unresectable, locally advanced NSCLC patients
SummaryThe aim of this prospective study is to evaluate the clinical use and real-world efficacy of durvalumab maintenance treatment after chemoradiotherapy (CRT) in unresectable stage, locally advanced non-small cell lung cancer (NSCLC). All consecutive patients with unresectable, locally advanced NSCLC and PD-L1 expression ( ≥1%) treated after October 2018 were included. Regular follow up, including physical examination, PET/CT and/or contrast-enhanced CT-Thorax/Abdomen were performed every three months after CRT. Descriptive treatment pattern analyses, including reasons of discontinuation and salvage treatment, were ...
Source: Investigational New Drugs - March 11, 2021 Category: Drugs & Pharmacology Source Type: research

Correction to: Association of XRCC3 rs1799794 polymorphism with survival of glioblastoma multiforme patients treated with combined radio-chemotherapy
A Correction to this paper has been published:https://doi.org/10.1007/s10637-021-01097-3 (Source: Investigational New Drugs)
Source: Investigational New Drugs - March 11, 2021 Category: Drugs & Pharmacology Source Type: research

Efficacy and safety of lurbinectedin and doxorubicin in relapsed small cell lung cancer. Results from an expansion cohort of a phase I study
SummaryBackground A phase I study found remarkable activity and manageable toxicity for doxorubicin (bolus) plus lurbinectedin (1-h intravenous [i.v.] infusion) on Day 1 every three weeks (q3wk) as second-line therapy in relapsed small cell lung cancer (SCLC). An expansion cohort further evaluated this combination.Patients and methods Twenty-eight patients with relapsed SCLC after no more than one line of cytotoxic-containing chemotherapy were treated: 18 (64%) with sensitive disease (chemotherapy-free interval [CTFI] ≥90 days) and ten (36%) with resistant disease (CTFI
Source: Investigational New Drugs - March 11, 2021 Category: Drugs & Pharmacology Source Type: research

A phase 1b study of the Notch inhibitor crenigacestat (LY3039478) in combination with other anticancer target agents (taladegib, LY3023414, or abemaciclib) in patients with advanced or metastatic solid tumors
This study demonstrated that crenigacestat combined with different anticancer agents (taladegib, LY3023414, or abemaciclib) was poorly tolerated, leading to lowered dosing and disappointing clinical activity in patients with advanced or metastatic solid tumors. NCT02784795 and date of registration: May 27, 2016. (Source: Investigational New Drugs)
Source: Investigational New Drugs - March 8, 2021 Category: Drugs & Pharmacology Source Type: research

A phase Ib, open label, dose escalation trial of the anti-CD37 monoclonal antibody, BI 836826, in combination with ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia
SummaryBI 836826 is a chimeric immunoglobulin G1 antibody targeting CD37, a transmembrane protein expressed on normal and malignant B cells. This open-label, phase Ib, dose-escalation study was conducted to determine the recommended phase II dose (RP2D) of BI 836826  + ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). Eligible patients received 420 mg/day of ibrutinib with escalating doses of BI 836826. BI 836826 was administered in 4-week cycles. After Cycle 12, patients achieving complete response (CR), CR with incomplete marrow recovery, or minimal residual disease-neg...
Source: Investigational New Drugs - March 8, 2021 Category: Drugs & Pharmacology Source Type: research

Rapamycin synergizes the cytotoxic effects of MEK inhibitor binimetinib and overcomes acquired resistance to therapy in melanoma cell lines in vitro
Conclusion In general, we provide the evidence that dual inhibition of mTOR and MEK could be promising for further preclinical investigations. (Source: Investigational New Drugs)
Source: Investigational New Drugs - March 8, 2021 Category: Drugs & Pharmacology Source Type: research

Identify potential miRNA-mRNA regulatory networks contributing to high-risk neuroblastoma
In this study, comprehensive bioinformatics analysis was used to identify the differentially expressed genes (DEG and DEM) between high-risk patients and non-high-risk patients, and it was identified that ADRB2 may affect the survival status of high-risk patients due to miR -30a-5p regulation. The GSE49710, GSE73517, and GSE121513 datasets were downloaded from the Gene Expression Synthesis (GEO) database, and DEG and DEM were selected. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were applied to the selected DEGs. The STRING database and Cytoscape software were used to construct prot...
Source: Investigational New Drugs - March 5, 2021 Category: Drugs & Pharmacology Source Type: research

Phase 1 cohort expansion study of LY3023414, a dual PI3K/mTOR inhibitor, in patients with advanced mesothelioma
CONCLUSION LY3023414 monotherapy (200  mg BID) demonstrated an acceptable and manageable safety profile with limited single-agent activity in patients with advanced mesothelioma.ClinicalTrials.gov identifier: NCT01655225;Date of registration: 19 July 2012. (Source: Investigational New Drugs)
Source: Investigational New Drugs - March 4, 2021 Category: Drugs & Pharmacology Source Type: research