High-dose methotrexate (HDMTX) therapy is an important component in treatment regimens for acute lymphoblastic leukemia (ALL). Courses are associated with a risk of renal injury, delayed elimination, and increased systemic toxicity. Recently hypoalbuminemia has been recognized as yet another risk factor.

In our previous study, we found that the Chk1 inhibitor prexasertib enhances the antitumour effect of the oral anticancer drug S-1 against pancreatic cancer cells. In this study, we investigated the effect of combining S-1 and ceralasertib, an oral inhibitor of ATR, which is located upstream of Chk1. Ceralasertib is currently being investigated in multiple clinical trials for various cancers.

OBI-888 is a humanized, monoclonal IgG1 antibody specific to the tumor-associated carbohydrate antigen Globo H. We conducted a phase I-II study of OBI-888 in patients with advanced cancer.

For drugs with a narrow therapeutic window, there is a delicate balance between efficacy and toxicity, thus it is pivotal to administer the right dose from the first administration onwards. Exposure of pemetrexed, a cytotoxic drug used in lung cancer treatment, is dictated by kidney function. To facilitate optimized dosing of pemetrexed, accurate prediction of drug clearance is pivotal. Therefore, the aim of this study was to investigate the performance of the kidney function biomarkers serum creatinine, cystatin C and pro-enkephalin in terms of predicting the elimination of pemetrexed.

Eribulin is an inhibitor of microtubule dynamics. It is not as highly protein bound as the taxanes and is less vulnerable to extrusion by P-glycoprotein in the blood-brain barrier (BBB). These features predict that eribulin could play an active role in managing brain tumors. Indeed, the small amount of published clinical data indicates eribulin may have some efficacy against breast cancer brain metastases. To better understand the potential of eribulin for treating brain tumors, we performed an intracerebral microdialysis study to determine the neuropharmacokinetics of eribulin in cancer patients undergoing tumor resection.

Regorafenib is an oral protein kinase inhinitor approved fot the treatment of metastatic colorecral cancer. We present a first successful case of desensitization in regorafenib-related fix-drug eruption in the literature.

Ruxolitinib (RUX), a Janus kinase 2 (JAK2) inhibitor, and lenalidomide (LEN), an immunomodulatory agent, have recently been proposed as a combined treatment for myelofibrosis (MF). This combination has demonstrated improved efficacy, safety, and tolerability compared to monotherapy. To further refine these findings, an efficient analytical tool is needed to simultaneously determine RUX and LEN concentrations in blood plasma. This tool would enable the study of their pharmacokinetics, drug-drug interactions, and therapeutic monitoring during MF therapy. Unfortunately, such a method has not been existed in the literature. This study presents the first HPLC method with UV detection for the simultaneous quantitation of RUX and LEN in plasma. The method was validated according to the ICH guidelines for bioanalytical method validation. It exhibited linearity in the concentration ranges of 10 to 3150 ng mL for RUX and 80 to 5200 ng mL for LEN. The limits of quantitation were determined to be 25 and 90 ng mL for RUX and LEN, respectively. All other validation parameters were satisfactory. The HPLC-UV method was successfully employed to study the pharmacokinetics and drug-drug interactions of RUX and LEN in rats following oral administration of single doses. The results demonstrated that the pharmacokinetics of both drugs were changed substantially by their coadministration. LEN exhibited synergistic effects on the maximum plasma concentration (C) and total bioavailability of RUX, meanwhile it exhibited diminishing effect on the values of volume of distribution (Vd) and clearance (CL). Additionally, RUX decreased the C and total bioavailability of LEN, meanwhile it increased its Vd and CL. These data suggest that the use of RUX, as a combination with LEN, is a better therapeutic approach for MF, compared with RUX as a monotherapy. The effects of LEN on the pharmacokinetics of RUX should be considered and can be useful in determining the appropriate RUX dosage and dosing regimen to achieve the desired therapeutic effect when used as a combination therapy with LEN. The method's environmental friendliness was confirmed through three comprehensive tools. This method represents a valuable tool for determining the appropriate dosage and dosing regimen of RUX in combination therapy with LEN to achieve the desired therapeutic effect. Furthermore, it can aid in predicting drug distribution in different patients and assessing the drug accumulation or insufficient drug levels in specific body compartments.

Osteosarcoma is a rare tumor with an incidence of 4.4 cases per million per year in adolescent. High-dose methotrexate (HD-MTX) is the standard first-line chemotherapeutic agent for osteosarcoma. However, its efficacy can vary significantly among individuals due to wide pharmacokinetic variability. Despite this, only a few population pharmacokinetics (popPK) models based on Chinese patients with osteosarcoma have been reported. Thus, this study aimed to develop a HD-MTX popPK model and an individual model-based dose optimizer for osteosarcoma therapy.

Triple-negative breast cancer (TNBC) represents the most aggressive subtype of breast cancer and is frequently resistant to therapy, ultimately resulting in treatment failure. Clinical trials have demonstrated the potential of sensitizing radiation therapy (RT)-resistant TNBC through the combination of chemotherapy and RT. This study sought to explore the potential of CD151 as a therapy response marker in the co-treatment strategy involving ionizing radiation (IR) and the repurposed antiviral drug 2-Thio-6-azauridine (TAU) for sensitizing RT-resistant TNBC (TNBC/RR).

The role of selinexor, a targeted inhibitor of exportin 1 (XPO1), in the treatment of cholangiocarcinoma is not yet fully understood. This study conducted comprehensive in vitro and in vivo investigations to elucidate the effects of selinexor on cholangiocarcinoma, with a focus on its mechanistic relationship with the cellular localization of Paternally Expressed Gene 3 (PEG3).

Overexpression of galectin-3, a β-galactoside-binding lectin, is associated with fibrotic diseases and cancer. Selvigaltin is an oral galectin-3 inhibitor, previously administered as a 50 mg capsule. This study aimed to evaluate the relative bioavailability and food effect of selvigaltin as a 100 mg tablet in healthy volunteers.

Trastuzumab is a potent targeted therapy drug for HER2-positive cancer patients. A comprehensive understanding of trastuzumab's mechanism of action, pharmacokinetic (PK) parameters, and steady-state exposure in different treatment regimens and administration routes is essential for a thorough evaluation of the drug's safety and effectiveness. Due to the distinctive pharmacokinetics, indications, and administration methods of trastuzumab, this understanding becomes crucial. Drug exposure can be assessed by measuring trastuzumab's peak concentration, trough concentration, or area under the curve through assays like enzyme-linked immunosorbent assay (ELISA) or liquid chromatography-tandem mass spectrometry (LC-MS/MS). The dose-response (D-R) and exposure-response (E-R) relationships establish the correlation between drug dosage/exposure and the therapeutic effect and safety. Additionally, various covariates such as body weight, aspartate transaminase, and albumin levels can influence drug exposure. This review provides a comprehensive overview of trastuzumab's mechanism of action, data on steady-state concentration and PK parameters under multiple administration routes and indications, discussions on factors influencing PK parameters, and evaluations of the effectiveness and safety of E-R and D-R in diverse HER2-positive cancer patients.

This study aimed to establish a population pharmacokinetic (PK) model to evaluate the dynamic relationship between the concentrations of total and unbound paclitaxel, and the exposure-response analysis of albumin-bound paclitaxel (nab-paclitaxel) after pegylated recombinant human granulocyte colony-stimulating factor (PEG-G-CSF) administration in patients with metastatic breast cancer.

Cisplatin and amphotericin B are both known to be potentially nephrotoxic. We describe acute kidney injury due to the combination of Liposomal amphotericin B and cisplatin in an adolescent with osteosarcoma. Acute kidney injury (peak creatinine 431 µmol/L) consistent with drug-induced acute tubulointerstitial nephritis was observed a few days after concomitant administration of cisplatin and amphotericin B. Kidney function nearly normalised during follow-up. The timing of the concomitant administration of amphotericin B and cisplatin led us to presume that the combination was the cause of renal failure, and we conclude that concurrent administration of cisplatin and amphotericin B should be avoided.

A physiologically based pharmacokinetic (PBPK) model for fedratinib was updated and revalidated to bridge a gap between the observed drug-drug interaction (DDI) of a single sub-efficacious dose in healthy participants and the potential DDI in patients with cancer at steady state. The study aimed to establish an appropriate dose for fedratinib in patients coadministered with dual CYP3A4 and CYP2C19 inhibitors, providing quantitative evidence to inform dosing guidance.

Midostaurin, approved for FLT3-mutated acute myeloid leukemia and advanced systemic mastocytosis, is mainly metabolized by cytochrome P450 (CYP) 3A4. Midostaurin exhibited potential inhibitory effects on P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic anion-transporting polyprotein 1B1, and CYP2D6 in in vitro studies. This study investigated the pharmacokinetic (PK) effects of midostaurin on P-gp (digoxin), BCRP (rosuvastatin) and CYP2D6 (dextromethorphan) substrates in healthy adults.

Hair cell damage is a common side effect caused by the anticancer drug cisplatin (CDDP), which reduces patient quality of life. One CDDP resistance mechanism that occurs in recurrent cancers is heavy metal detoxification by metallothionein-2 (mt2). Here, we show that in zebrafish larvae, dexamethasone (DEX) reduces CDDP-induced hair cell damage by enhancing mt2 expression.

Cancer stem cells (CSCs) account for recurrence and resistance to breast cancer drugs, rendering them a cause of mortality and therapeutic failure. In this study, we examined the effects of exposure to low concentrations of doxorubicin (Dox) on CSCs and non-CSCs from TNBC.

Osteosarcoma is the most common malignant bone tumor in children and adolescents. Conventional chemotherapy remains unsatisfactory due to drug toxicity and resistance issues. Therefore, there is an urgent need to develop more effective treatments for advanced osteosarcoma. In the current study, we focused on evaluating the anticancer efficacy of avermectin B1, a novel avermectin analog, against osteosarcoma cells.

Pancreatic ductal adenocarcinoma (PDAC) is among the most aggressive malignancies. Our previous work revealed Chitinase 3-like 1 (CHI3L1) involvement in PDAC resistance to gemcitabine, identifying it as a promising therapeutic target. Here, we aimed to identify putative CHI3L1 inhibitors and to investigate their chemosensitizing potential in PDAC.