First-in-human, open-label, phase 1/2 study of the monoclonal antibody programmed cell death protein-1 (PD-1) inhibitor cetrelimab (JNJ-63723283) in patients with advanced cancers
ConclusionsThe RP2D for cetrelimab was established. Pharmacokinetic/pharmacodynamic characteristics, safety profile, and clinical activity of cetrelimab in immune-sensitive advanced cancers were consistent with known PD-1 inhibitors.Trial registrationsNCT02908906 at ClinicalTrials.gov, September 21, 2016; EudraCT 2016 –002,017-22 at clinicaltrialsregister.eu, Jan 11, 2017. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 17, 2022 Category: Cancer & Oncology Source Type: research

Risk factors of proteinuria and potentially protective effect of renin –angiotensin system inhibitors in patients with renal cell carcinoma receiving axitinib
ConclusionIn patients with RCC receiving axitinib, pre-existing proteinuria and non-RAS inhibitor use were significantly associated with grade ≥ 2 proteinuria development. Our preliminary data should be confirmed by further studies. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 7, 2022 Category: Cancer & Oncology Source Type: research

Phase 1b trial of anti-VEGF/PDGFR vorolanib combined with immune checkpoint inhibitors in patients with advanced solid tumors
ConclusionCombination vorolanib 300  mg orally once daily plus CPI appears to be a feasible regimen with manageable toxicity and promising efficacy in select tumor types. NCT03511222. Date of Registration: April 18, 2018. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - March 5, 2022 Category: Cancer & Oncology Source Type: research

A clinical scoring tool validated with machine learning for predicting severe hand –foot syndrome from sorafenib in hepatocellular carcinoma
ConclusionA clinical prediction tool defined by female sex, high haemoglobin and low bilirubin had high discrimination for predicting HFS risk. The tool may enable improved evaluation of personalized risks of HFS for patients with advanced HCC initiating sorafenib. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - February 28, 2022 Category: Cancer & Oncology Source Type: research

Targeting Wee1 kinase to suppress proliferation and survival of cisplatin-resistant head and neck squamous cell carcinoma
ConclusionWee1 inhibitor, AZD1775, and cisplatin coordinately suppressed proliferation and survival of HNSCC. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - February 25, 2022 Category: Cancer & Oncology Source Type: research

Population pharmacokinetics of crenolanib in children and young adults with brain tumors
ConclusionsCrenolanib pharmacokinetics were adequately characterized in children and young adults with brain tumors. Despite marked increased drug exposure with acid reducer cotreatment, crenolanib therapy was well tolerated. No dosing adjustments are recommended for this population. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - February 25, 2022 Category: Cancer & Oncology Source Type: research

Disulfiram/copper induces antitumor activity against gastric cancer cells in vitro and in vivo by inhibiting S6K1 and c-Myc
ConclusionOur study demonstrated that DSF/Cu exerted antitumor activity against GC cells both in vitro and in vivo. DSF/Cu may represent a promising therapeutic strategy for the treatment of GC. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - February 24, 2022 Category: Cancer & Oncology Source Type: research

Retraction Note to: MicroRNA ‑30c‑regulated HDAC9 mediates chemoresistance of breast cancer
(Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - February 24, 2022 Category: Cancer & Oncology Source Type: research

SOX8 promotes cetuximab resistance via HGF/MET bypass pathway activation in colorectal cancer
ConclusionThe SOX8/HGF/MET axis played a crucial role in the communication between cetuximab-resistant cells and cetuximab-sensitive cells, inducing treatment resistance. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - February 23, 2022 Category: Cancer & Oncology Source Type: research

Hsp90 inhibition sensitizes DLBCL cells to cisplatin
ConclusionThis study demonstrates that 17AAG sensitizes DLBCL cells to cisplatin treatment. This effect is correlated with increased apoptotic and DNA damage response, potentially mediated by downregulation of Hsp90 clients in DNA repair pathways. Thus, cisplatin resistance could plausibly be overcome by combining the treatment with an Hsp90 inhibiting drug. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - February 21, 2022 Category: Cancer & Oncology Source Type: research

Isoprenylcysteine carboxyl methyltransferase is critical for glioblastoma growth and survival by activating Ras/Raf/Mek/Erk
ConclusionsOur findings provide the proof-of-concept of pharmacologically targeting ICMT in the treatment of glioblastoma via deactivation of Ras/Raf/Mek/Erk. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - February 16, 2022 Category: Cancer & Oncology Source Type: research

Cabozantinib with or without Panitumumab for RAS wild-type metastatic colorectal cancer: impact of MET amplification on clinical outcomes and circulating biomarkers
ConclusionThis study identified circulating HGF and several inflammatory and angiogenic proteins as prognostic biomarkers. Furthermore,MET amplification status is associated with both baseline expression and on-treatment modulation of members of angiogenesis and TGF- β pathway proteins.Clinical trials registration numberClinicalTrials.gov identifier: NCT02008383. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - February 16, 2022 Category: Cancer & Oncology Source Type: research

Evaluation of cytogenetic and molecular markers with MTX-mediated toxicity in pediatric acute lymphoblastic leukemia patients
ConclusionSLC19A1 facilitates the import of cyclic dinucleotides and reduced folates, evaluating genotypes in this gene can help in better management of patients on methotrexate treatment. Assessing a broader gene panel can help in finding more associated markers and delivering personalized medicine to the patients. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - February 14, 2022 Category: Cancer & Oncology Source Type: research

Cytotoxic mechanisms of doxorubicin at clinically relevant concentrations in breast cancer cells
AbstractDoxorubicin (DOX) is a chemotherapeutic agent frequently used for the treatment of a variety of tumor types, such as breast cancer. Despite the long history of DOX, the mechanistic details of its cytotoxic action remain controversial. Rather than one key mechanism of cytotoxic action, DOX is characterized by multiple mechanisms, such as (1) DNA intercalation and adduct formation, (2) topoisomerase II (TopII) poisoning, (3) the generation of free radicals and oxidative stress, and (4) membrane damage through altered sphingolipid metabolism. Many past reviews of DOX cytotoxicity are based on supraclinical concentrati...
Source: Cancer Chemotherapy and Pharmacology - February 12, 2022 Category: Cancer & Oncology Source Type: research

Prediction of drug –drug interaction potential mediated by transporters between dasatinib and metformin, pravastatin, and rosuvastatin using physiologically based pharmacokinetic modeling
ConclusionsThis PBPK model accurately described the observed PK profiles of dasatinib. The validated PBPK model predicts low risk of clinically significant DDIs between dasatinib and metformin, pravastatin, or rosuvastatin. (Source: Cancer Chemotherapy and Pharmacology)
Source: Cancer Chemotherapy and Pharmacology - February 11, 2022 Category: Cancer & Oncology Source Type: research