Secondary acquired nasolacrimal duct obstruction due to the toxic effect of antineoplastic agents

In recent years, the use of chemotherapeutic agents in the treatment of cancer became more common. At the same time, the number of complications associated with this is also increasing. Among the rare complications of therapy with some antitumor drugs is the formation of secondary acquired nasolacrimal duct obstruction. The aim was to analyze and systematize information about secondary acquired nasolacrimal duct obstruction due to the toxic effect of antitumor drugs. Materials and methods. The authors analyzed the literature available in the MEDLINE and RSCI search engines in February 2021. The analysis included 55 publications. Results. In the literature, there are indications that such antitumor drugs as 5-fluorouracil and similar drugs, mitomycin C, as well as therapy with radioactive iodine, are characterized by the possibility of developing complications in the form of secondary acquired nasolacrimal duct obstruction. Preliminary screening of the drainage function of the tear ducts, as well as prescribing of local anti-inflammatory and antibacterial treatment in the form of instillations in the conjunctival sac can help to reduce the risk of complications. This explains the need to recommend patients to consult an ophthalmologist if there are relevant complaints before or during treatment. In the absence of timely treatment, obstruction of the tear ducts often becomes an indication for reconstructive interventions. Conclusion. Secondary acquired nasolacrimal duct obstruction is one of the rare, but systematically occurring complications of antitumor therapy. To date, the pathogenesis of these complications is not fully understood, and some of the data is contradictory. In the future, the accumulation of knowledge concerning the pathogenesis of this complication will contribute to the development of personalized methods of prevention.

Recent Research Progress of Chiral Small Molecular Antitumor-Targeted Drugs Approved by the FDA From 2011 to 2019

Chiral drugs usually contain chiral centers, which are present as single enantiomers or racemates. Compared with achiral drugs, they have significant advantages in safety and efficacy with high stereoselectivity. Of these drugs, chirality not only exerts influence on the solubility and pharmacokinetic characteristics but also has specific mechanistic characteristics on their targets. We noted that small molecules with unique chiral properties have emerged as novel components of antitumor drugs approved by the FDA in decade. Since approved, these drugs have been continuously explored for new indications, new mechanisms, and novel combinations. In this mini review, recent research progress of twenty-two FDA-approved chiral small molecular-targeted antitumor drugs from 2011 to 2019 is summarized with highlighting the potential and advantages of their applications. We believe that these updated achievements may provide theoretical foundation and stimulate research interests for optimizing drug efficacy, expanding clinical application, overcoming drug resistance, and advancing safety in future clinical administrations of these chiral targeted drugs.

An Easily Expandable Multi-Drug LC-MS Assay for the Simultaneous Quantification of 57 Oral Antitumor Drugs in Human Plasma

Oral anticancer drugs have led to significant improvements in the treatment of multiple tumor entities. However, in patients undergoing oral antitumor therapy, plasma concentrations are highly variable, resulting in risks of reduced therapeutic effects or an increase in side effects. One important tool to reduce this variability is therapeutic drug monitoring. In this work we describe a method to simultaneously quantify the plasma concentrations of 57 oral antitumor agents. Quantification of these drugs was achieved using liquid chromatography coupled to an Orbitrap mass spectrometer. The method was fully validated according to the FDA guidelines and constitutes a simple and robust way for exposure monitoring of a wide variety of oral anticancer drugs. Applicability to clinical routine was demonstrated by the analysis of 71 plasma samples taken from 39 patients. In summary, this new multi-drug method allows simultaneous quantification of 57 oral antitumor drugs, which can be applied to exposure monitoring in clinical studies, taking into account the broad variety of oral antitumor drugs prescribed in clinical routine.

Tetramethylpyrazine: A Review of Its Antitumor Potential and Mechanisms

Cancer remains a major public health threat. The mitigation of the associated morbidity and mortality remains a major research focus. From a molecular biological perspective, cancer is defined as uncontrolled cell division and abnormal cell growth caused by various gene mutations. Therefore, there remains an urgent need to develop safe and effective antitumor drugs. The antitumor effect of plant extracts, which are characterized by relatively low toxicity and adverse effect, has attracted significant attention. For example, increasing attention has been paid to the antitumor effects of tetramethylpyrazine (TMP), the active component of the Chinese medicine Chuanqiong, which can affect tumor cell proliferation, apoptosis, invasion, metastasis, and angiogenesis, as well as reverse chemotherapeutic resistance in neoplasms, thereby triggering antitumor effects. Moreover, TMP can be used in combination with chemotherapeutic agents to enhance their effects and reduce the side effect associated with chemotherapy. Herein, we review the antitumor effects of TMP to provide a theoretical basis and foundation for the further exploration of its underlying antitumor mechanisms and promoting its clinical application.

Studies of Glyoxalase 1-Linked Multidrug Resistance Reveal Glycolysis-Derived Reactive Metabolite, Methylglyoxal, Is a Common Contributor in Cancer Chemotherapy Targeting the Spliceosome

BackgroundTumor glycolysis is a target for cancer chemotherapy. Methylglyoxal (MG) is a reactive metabolite formed mainly as a by-product in anaerobic glycolysis, metabolized by glyoxalase 1 (Glo1) of the glyoxalase system. We investigated the role of MG and Glo1 in cancer chemotherapy related in multidrug resistance (MDR).MethodsHuman Glo1 was overexpressed in HEK293 cells and the effect on anticancer drug potency, drug-induced increase in MG and mechanism of cytotoxicity characterized. Drug-induced increased MG and the mechanisms driving it were investigated and the proteomic response to MG-induced cytotoxicity explored by high mass resolution proteomics of cytoplasmic and other subcellular protein extracts. Glo1 expression data of 1,040 human tumor cell lines and 7,489 tumors were examined for functional correlates and impact of cancer patient survival.ResultsOverexpression of Glo1 decreased cytotoxicity of antitumor drugs, impairing antiproliferative activity of alkylating agents, topoisomerase inhibitors, antitubulins, and antimetabolites. Antitumor drugs increased MG to cytotoxic levels which contributed to the cytotoxic, antiproliferative mechanism of action, consistent with Glo1-mediated MDR. This was linked to off-target effects of drugs on glycolysis and was potentiated in hypoxia. MG activated the intrinsic pathway of apoptosis, with decrease of mitochondrial and spliceosomal proteins. Spliceosomal proteins were targets of MG modification. Spliceosomal gene expression correlated positively with Glo1 in human tumor cell lines and tumors. In clinical chemotherapy of breast cancer, increased expression of Glo1 was associated with decreased patient survival, with hazard ratio (HR) = 1.82 (logrank p < 0.001, n = 683) where upper quartile survival of patients was decreased by 64% with high Glo1 expression.ConclusionsWe conclude that MG-mediated cytotoxicity contributes to the cancer chemotherapeutic response and targets the spliceosome. High expression of Glo1 contributes to multidrug resistance by shielding the spliceosome from MG modification and decreasing survival in the chemotherapy of breast cancer. Adjunct chemotherapy with Glo1 inhibitor may improve treatment outcomes.

Tumor Microenvironment–Responsive Polypeptide Nanogels for Controlled Antitumor Drug Delivery

Tumor microenvironment–responsive polypeptide nanogels belong to a biomaterial with excellent biocompatibility, easily adjustable performance, biodegradability, and non-toxic properties. They are developed for selective delivery of antitumor drugs into target organs to promote tumor cell uptake, which has become an effective measure of tumor treatment. Endogenous (such as reduction, reactive oxygen species, pH, and enzyme) and exogenous (such as light and temperature) responsive nanogels can release drugs in response to tumor tissues or cells to improve drug distribution and reduce drug side effects. This article systematically introduces the research progress in tumor microenvironment–responsive polypeptide nanogels to deliver antitumor drugs and provides a reference for the development of antitumor nanoformulations.

The Neurotensinergic System: A Target for Cancer Treatment

Background: The scientific interest regarding the involvement of peptides in cancer has increased in the last years. In tumor cells the overexpression of peptides and their receptors is known and new therapeutic targets for the treatment of cancer have been suggested. The overexpression of the neurotensinergic system has been associated with poor prognosis, tumor size, higher tumor aggressiveness, increased relapse risk and worse sensitivity to chemotherapy agents. Objective: The aim of this review is to update the findings regarding the involvement of the neurotensinergic system in cancer to suggest anticancer therapeutic strategies targeting this system. The neurotensin (NT) precursor, NT and its receptors (NTR) and the involvement of the neurotensinergic system in lung, breast, prostate, gastric, colon, liver and pancreatic cancers, glioblastoma, neuroendocrine tumors and B-cell leukemia will be mentioned and discussed as well as the signaling pathways mediated by NT. Some research lines to be developed in the future will be suggested such as: molecules regulating the expression of the NT precursor, influence of the diet in the development of tumors, molecules and signaling pathways activated by NT and antitumor therapeutic strategies targeting the neurotensinergic system. Conclusion: NT, via the NTR, exerts oncogenic (tumor cell proliferation, invasion, migration, angiogenesis) and antiapoptotic effects, whereas NTR antagonists inhibit these effects. NTR expression can be used as a diagnostic tool/therapeutic target and the administration of NTR antagonists as antitumor drugs could be a therapeutic strategy to treat tumors overexpressing NTR.

Drugs associated with drug-induced pancreatitis: focus on rarely discussed drugs

More than 500 medicines are included in the database of the World Health Organization as drugs that can cause acute inflammation of the pancreas. Drug-induced acute pancreatitis develops against the background of taking many medications (statins, antitumor drugs, drugs for the treatment of diseases of the gastrointestinal tract, analgesics and anti-inflammatory drugs, antimicrobial, antiparasitic and antiviral drugs, drugs for the treatment of tuberculosis, diseases of the central nervous system, estrogens, calcium preparations, etc.) from different classes, while the clinical picture does not differ from pancreatitis of other etiology. Based on this, it is worth paying attention to the reasons that contributed to the development of this pathology. Therefore, one of the main principles of the diagnosis of drug-induced pancreatitis is a thorough collection of a pharmacological history. If you suspect that pancreatitis was caused by a drug, you should immediately stop using it and start traditional therapeutic treatment.

A Review on Drug Delivery System for Tumor Therapy

In recent years, with the development of nanomaterials, the research of drug delivery systems has become a new field of cancer therapy. Compared with conventional antitumor drugs, drug delivery systems such as drug nanoparticles (NPs) are expected to have more advantages in antineoplastic effects, including easy preparation, high efficiency, low toxicity, especially active tumor-targeting ability. Drug delivery systems are usually composed of delivery carriers, antitumor drugs, and even target molecules. At present, there are few comprehensive reports on a summary of drug delivery systems applied for tumor therapy. This review introduces the preparation, characteristics, and applications of several common delivery carriers and expounds the antitumor mechanism of different antitumor drugs in delivery carriers in detail which provides a more theoretical basis for clinical application of personalized cancer nanomedicine in the future.