The effects of two gold-N-heterocyclic carbene (NHC) complexes in ovarian cancer cells: a redox proteomic study
ConclusionsIn this study, we deepened the mode of action of Au(NHC) and Au(NHC)2PF6, identifying common cellular targets but confirming their different influence on the mitochondrial function. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - May 11, 2022 Category: Cancer & Oncology Source Type: research

Dose-dependent bioavailability, absorption-rate limited elimination, and tissue distribution of the ATR inhibitor BAY-1895344 (elimusertib) in mice
ConclusionsComplex PK behavior was limited to absorption processes which may not be recapitulated clinically. Tissue partition coefficients may be used to contrast ATR inhibitors with respect to their efficacy and toxicity. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - May 4, 2022 Category: Cancer & Oncology Source Type: research

Comparison of docetaxel pharmacokinetics between castration-resistant and hormone-sensitive metastatic prostate cancer patients
ConclusionThe PK profile of docetaxel was similar in mCPRC and mHSPC patients. Therefore, possible differences in toxicity between mCRPC and mHSPC patients cannot be explained by differences in docetaxel PK in our study population. These results suggest that treatment adaptations are not recommended in the new population of patients with mHSPC. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 25, 2022 Category: Cancer & Oncology Source Type: research

An evaluation of the interaction of pixantrone with formaldehyde-releasing drugs in cancer cells
ConclusionsThe features unique to pixantrone-DNA adducts may be leveraged to enhance cancer cell kill and may be used to guide the design of pixantrone analogues that generate adducts with more favorable anticancer properties. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 23, 2022 Category: Cancer & Oncology Source Type: research

Effectiveness and safety of sorafenib for renal cell, hepatocellular and thyroid carcinoma: pooled analysis in patients with renal impairment
ConclusionThe effectiveness and safety of sorafenib were similar in patients with eGFR  <  60 and ≥ 60 mL/min/1.73 m2 during the 12-month observation period, and without impairing renal function. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 20, 2022 Category: Cancer & Oncology Source Type: research

Feasibility of therapeutic drug monitoring of sunitinib and its implications on response and toxicity in patients with metastatic renal cell cancer
ConclusionThe TTL range of 60.75 –82.3 ng/mL was found to be optimal in terms of safety and efficacy. More than 50% of patients in our cohort attained TTL of sunitinib outside the optimal range, thus demonstrating the feasibility of TDM to improve safety and efficacy of sunitinib in mRCC. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 19, 2022 Category: Cancer & Oncology Source Type: research

Elimination of tucatinib, a small molecule kinase inhibitor of HER2, is primarily governed by CYP2C8 enantioselective oxidation of gem-dimethyl
ConclusionCYP2C8 and CYP3A4/5 are the primary drug-metabolizing enzymes involved in the in vitro metabolism of tucatinib, which provided the basis to describe human disposition of tucatinib and formation of the observed metabolites. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 18, 2022 Category: Cancer & Oncology Source Type: research

A phase 1 and pharmacodynamic study of chronically-dosed, single-agent veliparib (ABT-888) in patients with BRCA1- or BRCA2-mutated cancer or platinum-refractory ovarian or triple-negative breast cancer
ConclusionsContinuous veliparib is safe and tolerable. The RP2D was 400  mg BID. There is evidence of clinical activity of veliparib in patients withBRCAmut andBRCAwt cancers. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 18, 2022 Category: Cancer & Oncology Source Type: research

Assessment of cytochrome P450 3A4-mediated drug –drug interactions for ipatasertib using a fit-for-purpose physiologically based pharmacokinetic model
ConclusionThis study demonstrates the value of using a fit-for-purpose PBPK model to assess the clinical DDIs for ipatasertib and to provide dosing strategies for the concurrent use of other CYP3A4 perpetrators or victims. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 15, 2022 Category: Cancer & Oncology Source Type: research

Is age just a number? A population pharmacokinetic study of gemcitabine
ConclusionAge was not of influence on the pharmacokinetics of gemcitabine or its metabolite, dFdU. Age-related dose adjustments for gemcitabine based on pharmacokinetic considerations are not recommended.Trial registration numberNL39647.048.12, registered on May 3rd 2012. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 15, 2022 Category: Cancer & Oncology Source Type: research

An effective AKT inhibitor-PARP inhibitor combination therapy for recurrent ovarian cancer
ConclusionCollectively, our results suggest that the combination of AKT inhibitor and PARP inhibitor could be a viable approach for clinical testing in recurrent ovarian cancer patients. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 13, 2022 Category: Cancer & Oncology Source Type: research

Population pharmacokinetics of rucaparib in patients with advanced ovarian cancer or other solid tumors
ConclusionThe PPK model adequately described rucaparib PK, and none of the covariates evaluated had a clinically relevant effect.ClinicalTrials.govStudy 1014 (NCT01009190), Study 10 (NCT01482715), ARIEL2 (NCT01891344), ARIEL3 (NCT01968213), and TRITON2 (NCT02952534). (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 10, 2022 Category: Cancer & Oncology Source Type: research

Population pharmacokinetic analysis of tepotinib, an oral MET kinase inhibitor, including data from the VISION study
ConclusionsTepotinib shows dose proportionality up to at least the therapeutic dose, and time-independent clearance with a profile appropriate for once-daily dosing. None of the covariates identified had a clinically meaningful effect on tepotinib exposure or required dose adjustments. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 6, 2022 Category: Cancer & Oncology Source Type: research

PDI inhibitor LTI6426 enhances panobinostat efficacy in preclinical models of multiple myeloma
AbstractThe histone deacetylase inhibitor (HDACi), panobinostat (Pano), is approved by the United States Food and Drug Administration (FDA) and European Medicines Agency (EMA) for treatment of relapsed/refractory multiple myeloma (MM). Despite regulatory approvals, Pano is used on a limited basis in MM due largely to an unfavorable toxicity profile. The MM treatment landscape continues to evolve, and for Pano to maintain a place in that paradigm it will be necessary to identify treatment regimens that optimize its effectiveness, particularly those that permit dose reductions to eliminate unwanted toxicity. Here, we propose...
Source: Cancer Chemotherapy and Pharmacology - April 5, 2022 Category: Cancer & Oncology Source Type: research

Editorial Expression of Concern for: Induction of apoptosis by [6]-gingerol associated with the modulation of p53 and involvement of mitochondrial signaling pathway in B[a]P-induced mouse skin tumorigenesis
(Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - April 5, 2022 Category: Cancer & Oncology Source Type: research