A phase Ib study of sonidegib (LDE225), an oral small molecule inhibitor of smoothened or Hedgehog pathway, in combination with docetaxel in triple negative advanced breast cancer patients: GEICAM/2012 –12 (EDALINE) study
SummaryUp-regulation of the Hedgehog (Hh) pathway is implicated in the genesis of a wide range of tumors including triple negative breast cancer (TNBC). Sonidegib is a potent and selective oral inhibitor of Smo, a key component of the Hh signaling pathway. We designed a phase I clinical study to explore the combination of sonidegib plus docetaxel (fixed dose at 75  mg/m2) in advanced TNBC patients. The primary objective was to ascertain the combination ’s maximum tolerated dose and the recommended phase II dose (RP2D), based on dose limiting toxicities (DLTs) in the first 2 cycles. A standard “3&thins...
Source: Investigational New Drugs - June 9, 2018 Category: Drugs & Pharmacology Source Type: research

The poly (ADP-ribose) polymerase inhibitor rucaparib suppresses proliferation and serves as an effective radiosensitizer in cervical cancer
Conclusions Rucaparib exerts significant anti-proliferative effects and can serve as an effective radiosensitizer in cervical cancer, suggesting its candidacy in cervical cancer treatment and worthiness for further investigation. (Source: Investigational New Drugs)
Source: Investigational New Drugs - June 6, 2018 Category: Drugs & Pharmacology Source Type: research

Preclinical study of the antitumor effect of sphingosine-1-phosphate receptor 1 antibody (S1PR 1 -antibody) against human breast cancer cells
In this study, we evaluated whether a monoclonal antibody against S1PR1 (S1PR1-antibody) could impose any effect on cell growth of human breast cancer SK-BR-3 and MDA-MB-231 cells. The S1PR1-antibody exhibited cytostatic effect against both cell lines at the concentration of 4000  ng/mL. Co-administration of 4000 ng/mL of the S1PR1-antibody not only potentiated the cytotoxicity of carboplatin towards the MDA-MB-231 cells but also increased the anti-proliferative effect of S1P towards the SK-BR-3 cells. Furthermore, we showed that co-administration of S1P did not sensitize the SK-BR-3 and MDA-MB-231 cells towards ...
Source: Investigational New Drugs - June 2, 2018 Category: Drugs & Pharmacology Source Type: research

Hepatic safety analysis of trabectedin: results of a pharmacokinetic study with trabectedin in patients with hepatic impairment and experience from a phase 3 clinical trial
Conclusion Trabectedin treatment of patients with HI results in higher plasma exposures. Hepatotoxicity in patients with normal liver function can be effectively addressed through dose reductions and delays. (Source: Investigational New Drugs)
Source: Investigational New Drugs - May 11, 2018 Category: Drugs & Pharmacology Source Type: research

Translational PK-PD modeling analysis of MCLA-128, a HER2/HER3 bispecific monoclonal antibody, to predict clinical efficacious exposure and dose
Conclusions This analysis predicts that a flat dose of 10 to 480  mg q3wk is suitable as starting dose for a First-in-Human study with MCLA-128. Flat doses ≥360 mg q3wk are expected to be efficacious in human, based on receptor occupancies and PK-PD model simulations. (Source: Investigational New Drugs)
Source: Investigational New Drugs - May 5, 2018 Category: Drugs & Pharmacology Source Type: research

A multicentre, open-label phase II study of I rinotecan, capecitabine ( X eloda ®), and O xaliplatin (IXO) as first-line treatment in patients with metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma
Conclusion mIXO demonstrates promising ORR, PFS, OS, and acceptable toxicity compared to standard triplet regimens. IXO should be evaluated in phase III trials. (Source: Investigational New Drugs)
Source: Investigational New Drugs - May 4, 2018 Category: Drugs & Pharmacology Source Type: research

Crizotinib-induced simultaneous multiple cardiac toxicities
SummaryCrizotinib is a receptor tyrosine kinase inhibitor that has several targets, including c-ros oncogene 1 and the MET proto-oncogene. Considering its known cardiac toxicity, bradycardia is often investigated following treatment with crizotinib. Our patients had bradycardia, QT prolongation, ventricular rhythm, ventricular fibrillation, and pericarditis simultaneously. The cardiotoxicity of crizotinib can sometimes be simultaneous; thus, intensive observation is needed. (Source: Investigational New Drugs)
Source: Investigational New Drugs - May 2, 2018 Category: Drugs & Pharmacology Source Type: research

Successful oral desensitization with osimertinib following osimertinib-induced fever and hepatotoxicity: a case report
In conclusion, oral desensitization may be a useful method in treating hepatotoxicity and drug fever caused by osimertinib. (Source: Investigational New Drugs)
Source: Investigational New Drugs - May 2, 2018 Category: Drugs & Pharmacology Source Type: research

Human acute myeloid leukemia cells express Neurokinin-1 receptor, which is involved in the antileukemic effect of Neurokinin-1 receptor antagonists
SummaryThe substance P/neurokinin-1 receptor system has been implicated in tumor cell proliferation. Neurokinin-1 receptor has been identified in different solid tumors but not frequently in hematopoietic malignant cells. We investigated the presence of the Neurokinin-1 receptor in acute myeloid leukemia cell lines (KG-1 and HL-60), demonstrating that acute myeloid leukemia cell lines overexpress the truncated Neurokinin-1 receptor isoform compared with lymphocytes from healthy donors. Using the MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) method, we demonstrated that subst...
Source: Investigational New Drugs - May 2, 2018 Category: Drugs & Pharmacology Source Type: research

Inhibiting IL-2 signaling and the regulatory T-cell pathway using computationally designed peptides
Conclusions We conclude that structure-based peptide design can be used to identify novel peptide inhibitors that block IL-2/sIL-2R α signaling and inhibit Treg cell development. We anticipate that these peptides will have therapeutic potential in B-cell NHL and other malignancies. (Source: Investigational New Drugs)
Source: Investigational New Drugs - April 26, 2018 Category: Drugs & Pharmacology Source Type: research

Two phase I, pharmacokinetic, and pharmacodynamic studies of DFP-10917, a novel nucleoside analog with 14-day and 7-day continuous infusion schedules
Conclusion Continuous infusion of DFP-10917 is feasible and well tolerated with myelosuppression as main DLT. The recommended doses are 2.0  mg/m2/day and 3.0  mg/m2/day on the 14-day and 7-day continuous infusion schedules, respectively. Preliminary activity was suggested. Pharmacodynamic data demonstrate biological activity at the tested doses. (Source: Investigational New Drugs)
Source: Investigational New Drugs - April 18, 2018 Category: Drugs & Pharmacology Source Type: research

Optimising intratumoral treatment of head and neck squamous cell carcinoma models with the diterpene ester Tigilanol tiglate
This study confirmed that TT in 40% PG given intratumorally as a single bolus dose was the most efficacio us treatment for a tongue SCC mouse model. (Source: Investigational New Drugs)
Source: Investigational New Drugs - April 18, 2018 Category: Drugs & Pharmacology Source Type: research

Unique characteristics of regulatory approval and pivotal studies of orphan anticancer drugs in Japan
SummaryThe approval of orphan anticancer drugs has increased, with the number exceeding that of non-orphan drugs in Japan in recent years. Although orphan anticancer drugs may have unique characteristics due to their rarity, these have not been fully characterized. We investigated anticancer drugs approved in Japan between April 2004 and November 2017 to reveal the characteristics of regulatory approval and pivotal studies on orphan anticancer drugs compared to non-orphan drugs. The median regulatory review time and number of patients in pivotal studies on orphan anticancer drugs (281.0  days [interquartile range, 263...
Source: Investigational New Drugs - April 17, 2018 Category: Drugs & Pharmacology Source Type: research

A multi-arm phase I dose escalating study of an oral NOTCH inhibitor BMS-986115 in patients with advanced solid tumours
Conclusion The daily oral dosing of BMS-986115 is safe and tolerable with biological activity demonstrated by continuous target engagement and Notch signalling inhibition. (Source: Investigational New Drugs)
Source: Investigational New Drugs - April 10, 2018 Category: Drugs & Pharmacology Source Type: research

Nivolumab-induced acute granulomatous tubulointerstitial nephritis in a patient with gastric cancer
SummaryWe here report a case of nivolumab-induced acute granulomatous tubulointerstitial nephritis in a patient with gastric cancer. A 68-year-old woman with recurrent gastric cancer developed acute kidney injury associated with kidney enlargement and urinary leukocytes after 38  cycles of nivolumab treatment. A diagnosis of acute granulomatous tubulointerstitial nephritis was made based on kidney biopsy findings. Immunohistochemistry revealed expression of programmed cell death–ligand 1 (PD-L1) in degenerated epithelial cells of collecting tubules. Among infiltrating im mune cells, aggregation of T cells was mo...
Source: Investigational New Drugs - April 6, 2018 Category: Drugs & Pharmacology Source Type: research

A phase I, open-label, two-stage study to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of the oral AKT inhibitor GSK2141795 in patients with solid tumors
Conclusion GSK2141795 was safe and well-tolerated, with clinical activity seen as monotherapy at the RP2D of 75  mg daily. NCT00920257. (Source: Investigational New Drugs)
Source: Investigational New Drugs - April 3, 2018 Category: Drugs & Pharmacology Source Type: research

Nab -paclitaxel plus gemcitabine versus FOLFIRINOX as the first-line chemotherapy for patients with metastatic pancreatic cancer: retrospective analysis
Conclusion Both AG and FOLFIRINOX showed comparable efficacy outcomes in daily practice setting. AG might be preferentially considered in patients with peritoneal metastasis, comorbid medical conditions or old age. (Source: Investigational New Drugs)
Source: Investigational New Drugs - April 3, 2018 Category: Drugs & Pharmacology Source Type: research

Sirolimus enhances remission induction in patients with high risk acute myeloid leukemia and mTORC1 target inhibition
Conclusions Fixed, whole blood pS6 by flow cytometry may be a predictive biomarker for clinical response to mTORC1 inhibitor-based regimens. These data provide clinical confirmation that mTORC1 activation mediates chemotherapy resistance in patients with AML. (Source: Investigational New Drugs)
Source: Investigational New Drugs - April 2, 2018 Category: Drugs & Pharmacology Source Type: research

New NO- and H2S-releasing doxorubicins as targeted therapy against chemoresistance in castration-resistant prostate cancer: in vitro and in vivo evaluations
SummaryChemotherapy for castration-resistant prostate cancer (CRPC) is only temporarily effective due to the onset of chemoresistance. We investigated the efficacy of NO- and H2S-releasing doxorubicins (NitDox and H2SDox) in overcoming drug resistance and evaluated their safety. New and innovative NO- and H2S-releasing doxorubicins (NitDox and H2SDox) showed a good intracellular accumulation and high cytotoxic activity in vitro in an androgen-independent and doxorubicin-resistant DU-145 prostate cancer cell line. Nude mice were subcutaneously injected with 4*106 DU-145 cells and treated once a week for 3 weeks with 5  ...
Source: Investigational New Drugs - April 2, 2018 Category: Drugs & Pharmacology Source Type: research

Autophagy inhibition improves the chemotherapeutic efficacy of cruciferous vegetable-derived diindolymethane in a murine prostate cancer xenograft model
In conclusion, we have conf irmed that DIM and 4,4'-Br2DIM are effective agents against prostate cancer in vivo and shown that inhibition of autophagy with CQ enhances the anticancer efficacy of DIM. Our results suggest that including selective autophagy inhibitors as adjuvants may improve the efficacy of existing and novel drug therapies against prostate cancer. (Source: Investigational New Drugs)
Source: Investigational New Drugs - April 2, 2018 Category: Drugs & Pharmacology Source Type: research

Antitumor activity of raloxifene-targeted poly(styrene maleic acid)-poly (amide-ether-ester-imide) co-polymeric nanomicelles loaded with docetaxel in breast cancer-bearing mice
Discussion All studies in this work showed the potential of DTX-loaded SMA-PAEEI-PEG-RA micelles in the treatment of GPER-positive receptor breast cancer tumors. (Source: Investigational New Drugs)
Source: Investigational New Drugs - March 26, 2018 Category: Drugs & Pharmacology Source Type: research

A phase I/II trial of pemetrexed plus radiotherapy in elderly patients with locally advanced non-small cell lung cancer
Conclusions Combination PEM and RT shows promising efficacy but relatively severe RT-related toxicities. Therefore, this treatment should be prescribed to elderly patients with caution.Trial registration UMIN 000005036. (Source: Investigational New Drugs)
Source: Investigational New Drugs - March 23, 2018 Category: Drugs & Pharmacology Source Type: research

Post-progression survival following second-line chemotherapy in patients with advanced pancreatic cancer previously treated with gemcitabine: a meta-analysis
This study aimed to improve the understanding of the impact of PPS on OS in this setting.Methods Databases were searched to identify randomized controlled trials (RCTs) in the salvage setting. We evaluated relationships between OS and PFS, PPS, and other variables.Results Totally, 17 RCTs with 3253 patients were identified. Median OS was strongly and moderately associated with median PPS and PFS, respectively (r = 0.913;p 
Source: Investigational New Drugs - March 23, 2018 Category: Drugs & Pharmacology Source Type: research

The molecular mechanism of anticancer action of novel octahydropyrazino[2,1-a:5,4-a ′]diisoquinoline derivatives in human gastric cancer cells
Conclusion These data strongly support compound 2 as a promising molecule for treatment of gastric cancer. (Source: Investigational New Drugs)
Source: Investigational New Drugs - March 17, 2018 Category: Drugs & Pharmacology Source Type: research

Successful treatment with an EGFR tyrosine kinase inhibitor Afatinib in a patient with combined small-cell lung Cancer with EGFR mutation
SummarySmall-cell lung cancer (SCLC) combined with epidermal growth factor receptor (EGFR) mutations is extremely rare, and standard chemotherapeutic strategies have not yet been established. In the present study, we report a case of a 67-year-old man who presented with combined SCLC withEGFR mutation (exon 19 deletion). Systemic chemotherapy with cisplatin and irinotecan was initiated as first-line chemotherapy, and computed tomography findings revealed tumor shrinkage after two cycles of chemotherapy. However, after the third cycle of the treatment, disease progression was observed including the appearance of pleural and...
Source: Investigational New Drugs - March 15, 2018 Category: Drugs & Pharmacology Source Type: research

Clinical predictors of bevacizumab-associated intestinal perforation in non-small cell lung cancer
Conclusions Among patients with NSCLC, BAP was associated with deteriorating PS during the first cycle of chemotherapy, grade  ≥ 3 diarrhea, febrile neutropenia, and stomatitis. Therefore, careful observation is needed for patients with NSCLC who receive Bev in any line of treatment, especially if they develop serious side effects that affect their PS or mucous membrane. (Source: Investigational New Drugs)
Source: Investigational New Drugs - March 14, 2018 Category: Drugs & Pharmacology Source Type: research

Phase II trial of ifosfamide in combination with the VEGFR inhibitor sorafenib in advanced soft tissue sarcoma: a Spanish group for research on sarcomas (GEIS) study
Conclusion Treatment with sorafenib plus ifosfamide achieved a significant clinical benefit with an acceptable safety profile in patients with advanced soft tissue sarcoma resistant to anthracyclines, which warrants a more detailed study in randomized clinical trials. (Source: Investigational New Drugs)
Source: Investigational New Drugs - March 12, 2018 Category: Drugs & Pharmacology Source Type: research

Phase I study of CKD-581, a pan-histone deacetylase inhibitor, in patients with lymphoma or multiple myeloma refractory to standard therapy
Conclusion CKD-581 was well tolerated by the patients with lymphoma or MM refractory to standard therapy. It exhibited dose-proportional pharmacokinetics and modest anti-tumor efficacy. (Source: Investigational New Drugs)
Source: Investigational New Drugs - March 9, 2018 Category: Drugs & Pharmacology Source Type: research

A call for improved transparency in financial aspects of clinical trials: a case study of the CREATE-X trial in the New England Journal of Medicine
Conclusion This case report highlights the lack of financial transparency in the CREATE-X trial, and discusses the potential limitations that may exist in the current frameworks for disclosing financial ties between physicians and relevant industries in clinical trials. Achieving improved transparency is essential to heighten credibility in the findings of clinical trials. (Source: Investigational New Drugs)
Source: Investigational New Drugs - March 8, 2018 Category: Drugs & Pharmacology Source Type: research

Ruxolitinib + capecitabine in advanced/metastatic pancreatic cancer after disease progression/intolerance to first-line therapy: JANUS 1 and 2 randomized phase III studies
Conclusions Ruxolitinib plus capecitabine was well tolerated in refractory pancreatic cancer patients; this combination did not improve survival. (Source: Investigational New Drugs)
Source: Investigational New Drugs - March 6, 2018 Category: Drugs & Pharmacology Source Type: research

Inhibition of Rb and mTOR signaling associates with synergistic anticancer effect of palbociclib and erlotinib in glioblastoma cells
SummaryGenomic studies have established a set of three core-signaling pathways, receptor tyrosine kinase (RTK), p53 and retinoblastoma (Rb) signaling pathways, contributing glioblastoma (GBM) and revealed that dysregulation of at least two pathways is required for GBM progression. In the present study, we investigate efficacy of combination of palbociclib, cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, and erlotinib, epidermal growth factor receptor (EGFR) inhibitor in GBM cell systems with different p53 status. Cell proliferation and colony formation assays showed that the combination treatment synergistically suppressed...
Source: Investigational New Drugs - March 6, 2018 Category: Drugs & Pharmacology Source Type: research

A phase II study of the dual mTOR inhibitor MLN0128 in patients with metastatic castration resistant prostate cancer
Conclusions Clinical efficacy of MLN0128 in mCRPC was limited likely due to dose reductions secondary to toxicity, PSA kinetics suggesting AR activation resulting from mTOR inhibition, and poor inhibition of mTOR signaling targets. (Source: Investigational New Drugs)
Source: Investigational New Drugs - March 6, 2018 Category: Drugs & Pharmacology Source Type: research

Histone deacetylase inhibitor chidamide induces growth inhibition and apoptosis in NK/T lymphoma cells through ATM-Chk2-p53-p21 signalling  pathway
SummaryWe investigated the anti-tumour effects and the underlying molecular mechanisms of a new oral histone deacetylase inhibitor (HDACi), chidamide, in NK/T cell lymphoma (NKTCL), a rare and highly aggressive non-Hodgkin lymphoma with poor outcomes. SNT-8 and SNK-10 NKTCL cell lines were exposed to different concentrations of chidamide for the indicated time. The treated cells were analysed for cell proliferation, cell cycle progression, and cell apoptosis. Proteins in the AKT/mTOR and MAPK signalling pathways and the DNA damage response (DDR) cell cycle checkpoint pathway were measured by Western blotting. Chidamide inh...
Source: Investigational New Drugs - March 5, 2018 Category: Drugs & Pharmacology Source Type: research

PIK3CA mutation sensitizes breast cancer cells to synergistic therapy of PI3K inhibition and AMPK activation
SummaryBreast cancer has been emerging as a most common threat among women, thus many efforts were made to find drugs for fighting breast cancer. So far, PI3K (Phosphatidylinositol-4,5-bisphosphate 3-kinase) inhibitors have been believed to be effective drugs until frequent resistance emerged. Recently, PI3K H1047R mutation has been reported to sensitize breast cancer cells to PI3K inhibition by aspirin. Considering aspirin activates AMPK (AMP-activated protein kinase) simultaneously, it is possible that AMPK activators and PI3K inhibitors can synergistically inhibit breast cancers. Here we clearly observed synergistic sup...
Source: Investigational New Drugs - March 5, 2018 Category: Drugs & Pharmacology Source Type: research

Preclinical investigation of a potent geranylgeranyl diphosphate synthase inhibitor
SummaryGeranylgeranyl diphosphate synthase (GGDPS) is the enzyme in the isoprenoid biosynthesis pathway that catalyzes the synthesis of the 20-carbon isoprenoid GGPP, which serves as the isoprenoid donor for protein geranylgeranylation reactions. Rab proteins mediate vesicle trafficking within the cell and their activity is dependent on geranylgeranylation. Our prior work has demonstrated that agents that disrupt Rab geranylgeranylation disrupt monoclonal protein trafficking in myeloma cells, resulting in induction of the unfolded protein response pathway and apoptosis. VSW1198 is a potent GGDPS inhibitor with measurable c...
Source: Investigational New Drugs - March 2, 2018 Category: Drugs & Pharmacology Source Type: research

Pharmacokinetic analysis of metronomic capecitabine in refractory metastatic colorectal cancer patients
In conclusion, low doses of capecitabine were rapidly absorbed and extensively metabolized, achieving measurable plasma concentrations in a heavily pretreated population of patients. (Source: Investigational New Drugs)
Source: Investigational New Drugs - February 27, 2018 Category: Drugs & Pharmacology Source Type: research

A phase 2 study of OSI-906 (linsitinib, an insulin-like growth factor receptor-1 inhibitor) in patients with asymptomatic or mildly symptomatic (non-opioid requiring) metastatic castrate resistant prostate cancer (CRPC)
Conclusions Single-agent linsitinib was safe and well tolerated but failed to show activity in men with mCRPC. These results highlight the complexity of using IGF-1R as a therapeutic target in this patient population.ClinicalTrials.gov NCT01533246. (Source: Investigational New Drugs)
Source: Investigational New Drugs - February 23, 2018 Category: Drugs & Pharmacology Source Type: research

The concomitant use of lapatinib and paracetamol - the risk of interaction
SummaryLapatinib is a tyrosine kinase inhibitor used for the treatment of breast cancer. Paracetamol is an analgesic commonly applied to patients with mild or moderate pain and fever. Cancer patients are polymedicated, which involves high risk of drug interactions during therapy. The aim of the study was to assess the interaction between lapatinib and paracetamol in rats. The rats were divided into three groups of eight animals in each. One group received lapatinib + paracetamol (IL  + PA), another group received lapatinib (IIL), whereas the last group received paracetamol (IIIPA). A single dose of lapatinib ...
Source: Investigational New Drugs - February 20, 2018 Category: Drugs & Pharmacology Source Type: research

Pazopanib-related tumor lysis syndrome in metastatic clear cell renal cell carcinoma: a case report
Conclusion As far as we know this is the first report on pazopanib induced TLS. We advise further research in order to identify the exact mechanism behind TKI-induced TLS and the patients at risk of developing TLS. (Source: Investigational New Drugs)
Source: Investigational New Drugs - February 20, 2018 Category: Drugs & Pharmacology Source Type: research

Involvement of NF- κB in mediating the anti-tumour effects of combretastatins in T cells
Conclusions Our data indicate that the anti-cancer properties of comebretastatins may be mediated in part through targeting the NF- κB pathway. This study provides new insights into the molecular mechanisms of CA compounds and a potential application of combretastatins for inflammatory diseases such as cancers, which are associated with abnormal NF-κB activation. (Source: Investigational New Drugs)
Source: Investigational New Drugs - February 19, 2018 Category: Drugs & Pharmacology Source Type: research

Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study
Conclusions The manageable safety profile of IMGN529 and preliminary evidence of activity, particularly in DLBCL patients, support the continued development of this novel CD37-targeting agent. (Source: Investigational New Drugs)
Source: Investigational New Drugs - February 17, 2018 Category: Drugs & Pharmacology Source Type: research

Drug approval based on randomized phase 3 trials for relapsed malignancy: analysis of oncologic drugs granted accelerated approval, publications and clinical trial databases
Conclusion Our analysis indicates that drug approval based on phase 3 trials is more challenging for relapsed hematological malignancies than for solid malignancies. Therefore, determining proper evaluation methods for the efficacy and safety of drugs for relapsed malignancy, without randomized trials, is important. (Source: Investigational New Drugs)
Source: Investigational New Drugs - February 17, 2018 Category: Drugs & Pharmacology Source Type: research

A phase I and pharmacokinetic study of taladegib, a Smoothened inhibitor, in Japanese patients with advanced solid tumors
Conclusions Taladegib doses of 100  mg and 200 mg, but not the global recommended dose of 400 mg, were well tolerated in this population of Japanese patients with advanced solid tumors. (Source: Investigational New Drugs)
Source: Investigational New Drugs - February 17, 2018 Category: Drugs & Pharmacology Source Type: research

Proteasome inhibition and mechanism of resistance to a synthetic, library-based hexapeptide
Conclusion 4A6 is a novel specific inhibitor of the β5 subunit-associated chymotrypsin-like proteasome activity. Further exploration of 4A6 as a lead compound for development as a novel proteasome-targeted drug is warranted. (Source: Investigational New Drugs)
Source: Investigational New Drugs - February 14, 2018 Category: Drugs & Pharmacology Source Type: research

Pre-clinical effects of metformin and aspirin on the cell lines of different breast cancer subtypes
Conclusion We have provided novel evidence on the mechanisms of action of aspirin and metformin in breast cancer cells, showing favorable outcomes for these drugs in the ER+ and TNBC subtypes. (Source: Investigational New Drugs)
Source: Investigational New Drugs - February 2, 2018 Category: Drugs & Pharmacology Source Type: research

The HSP90 inhibitor NVP-AUY922 inhibits growth of HER2 positive and trastuzumab-resistant breast cancer cells
In conclusion, our data shows that NVP-AUY922 displays potent anti-cancer activity in HER2-positive and trastuzumab-resistant breast cancer cells, and supports further testing of NVP-AUY922 in patients with HER2-positive breast cancer. (Source: Investigational New Drugs)
Source: Investigational New Drugs - February 2, 2018 Category: Drugs & Pharmacology Source Type: research

Phase II study of doxorubicin and thalidomide in patients with refractory aggressive fibromatosis
Conclusions ADM plus THA was well-tolerated and effective as a first-line treatment for patients with refractory AF. However, patients with hypoalbuminemia at baseline had inferior clinical outcomes, and further studies are needed to investigate this issue. (Source: Investigational New Drugs)
Source: Investigational New Drugs - February 1, 2018 Category: Drugs & Pharmacology Source Type: research

SMER28 is a mTOR-independent small molecule enhancer of autophagy that protects mouse bone morrow and liver against radiotherapy
In this study, we investigated the effect of the mTOR-independent small molecule enhancer of autophagy (SMER28) on mouse liver autophagy and post-irradiation recovery of mouse bone marrow and liver. SMER28 enhanced the autophagy flux and improved the survival of normal hepatocytes. This effect was specific for normal cells because SMER28 had no protective effect on hepatoma or other cancer cell line survival in vitro. In vivo subcutaneous administration of SMER28 protected mouse liver and bone marrow against radiation damage and facilitated survival of mice after lethal whole body or abdominal irradiation. These findings o...
Source: Investigational New Drugs - January 31, 2018 Category: Drugs & Pharmacology Source Type: research

First-in-human phase I dose escalation study of MK-8033 in patients with advanced solid tumors
Conclusion MK-8033 was well tolerated with no significant toxicity issues, albeit with limited clinical activity. Unfortunately, the company decided to discontinue further clinical development of MK-8033. (Source: Investigational New Drugs)
Source: Investigational New Drugs - January 29, 2018 Category: Drugs & Pharmacology Source Type: research

Acknowledgement of Reviewers 2017
(Source: Investigational New Drugs)
Source: Investigational New Drugs - January 29, 2018 Category: Drugs & Pharmacology Source Type: research