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The pathogenesis, diagnosis, prevention, and treatment of CAR-T cell therapy-related adverse reactions.

Chimeric antigen receptor (CAR)-T cell therapy is effective in the treatment of refractory/relapsed (r/r) hematological malignancies (r/r B-cell lymphoblastic leukemia, B-cell lymphoma, and multiple myeloma). In addition, it is being explored as a treatment option for solid tumors. As of 31 March 2022, seven CAR-T therapies for hematological malignancies have been approved worldwide. Although CAR-T therapy is an effective treatment for many malignancies, it also causes adverse effects. The incidence of cytokine release syndrome (CRS), the most common adverse reaction after infusion of CAR-T ce

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… Commonly used “suicide switches” include inducible caspase 9 (iC9), herpes simplex virus thymidine kinase (HSV-TK), CD20, and truncated epidermal growth factor receptor (EGFRt) ( Gargett and Brown, 2014 ; Greco et al., 2015 ; Yu et al., 2019 ; Klopp et al., 2021 ; Warda et al., 2021 ). …

Combating Methotrexate Resistance in Cancer Treatment: A Review on Navigating Pathways and Enhancing Its Efficacy With Fat-Soluble Vitamins.

Methotrexate (MTX), a potent analogue and antagonist of folic acid, is a first-line treatment for rheumatoid arthritis, IBD and cancer. The development of MTX resistance contributes to the reduced efficacy and development of adverse reactions, forcing clinicians to withdraw treatment early. This drawback requires combinational approaches to combat the resistance and enhance the efficacy and safety of MTX. To provide a brief overview of MTX resistance and strategies to mitigate its aftereffects in cancer therapy, a literature-based search was conducted using keywords such as cancer pathology, M

Narrative Review of Drug-Associated Nail Toxicities in Oncologic Patients.

IntroductionNail toxicity represents one of the most common cutaneous adverse effects of both classic chemotherapeutic agents and new oncologic drugs, including targeted treatments and immunotherapy.ObjectivesWe aimed to provide a comprehensive literature review of nail toxicities derived from conventional chemotherapeutic agents, targeted therapies (EGFR inhibitors, multikinase inhibitors, BRAF and MEK inhibitors) and immune checkpoint inhibitors (ICIs), including clinical presentation, implicated drugs and approaches for prevention and management.MethodsRetrieved literature from PubMed regis

Boron Chemicals in Drug Discovery and Development: Synthesis and Medicinal Perspective.

A standard goal of medicinal chemists has been to discover efficient and potent drug candidates with specific enzyme-inhibitor abilities. In this regard, boron-based bioactive compounds have provided amphiphilic properties to facilitate interaction with protein targets. Indeed, the spectrum of boron-based entities as drug candidates against many diseases has grown tremendously since the first clinically tested boron-based drug, Velcade. In this review, we collectively represent the current boron-containing drug candidates, boron-containing retinoids, benzoxaboroles, aminoboronic acid, carboran

Molecular Targeting and Rational Chemotherapy in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a molecularly complex disease with multiple aberrant genetic pathways involved in its pathogenesis. Approximately one-third to one-half of patients with AML would relapse, and no standard therapy is established for relapsing and/or refractory AML (RR-AML) yet. It is unlikely that blockage of only one specific pathway will lead to prolonged remissions and cures in all fractions of the AML patients population. Nowadays, novel therapeutic agents with rational combination are being recognized which improve the cure rate for relapsed AML. These drugs and their metabo

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… In this regard, the primary target of the deoxynucleoside analogues is the DNA polymerases involved in DNA replication. 12 , 13 , 21 Although there are five kinase enzymes in human cells phosphorylating deoxynucleoside analogues (eg deoxycytidine and deoxyguanosine kinase, thymidine kinase 1/2, and 5 …

Cell-based medicinal products approved in the European Union: current evidence and perspectives.

Advanced Therapy Medicinal Products (ATMPs) are innovative clinical treatments exploiting the pharmacological, immunological, or metabolic properties of cells and/or gene(s) with the aim to restore, correct, or modify a biological function in the recipient. ATMPs are heterogeneous medicinal products, developed mainly as individualized and patient-specific treatments, and represent new opportunities for diseases characterized by a high-unmet medical need, including rare, genetic and neurodegenerative disorders, haematological malignancies, cancer, autoimmune, inflammatory and orthopaedic condit

m6A reader hnRNPA2B1 drives multiple myeloma osteolytic bone disease.

Rationale: Bone destruction is a hallmark of multiple myeloma (MM) and affects more than 80% of patients. Although previous works revealed the roles of N6-methyladenosine (m6A) reader hnRNPA2B1 in the development of tumors, whether hnRNPA2B1 regulates bone destruction in MM is still unknown. Methods: Alizarin red S staining, TRAP staining, ELISA and quantitative real-time PCR assays were used to evaluate osteogenesis and osteoclastogenesis in vitro. X ray and bone histomorphometric analysis were preformed to identify bone resorption and bone formation in vivo. Exosome isolation and characteriz

Mechanism of the susceptibility of remodeled pulmonary vessels to drug-induced cell killing.

BackgroundPulmonary arterial hypertension remains a devastating disease without a cure. The major complication of this disease is the abnormal growth of vascular cells, resulting in pulmonary vascular remodeling. Thus, agents, which affect the remodeled vessels by killing unwanted cells, should improve treatment strategies. The present study reports that antitumor drugs selectively kill vascular cells in remodeled pulmonary vessels in rat models of pulmonary hypertension.Methods and resultsAfter developing pulmonary vascular remodeling in chronic hypoxia or chronic hypoxia/SU-5416 models, rats

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… B, PASMCs were transfected with 3.2 kb or 0.6 kb bcl‐x promoter‐controlled firefly luciferase with renilla luciferase controlled by thymidine kinase (TK) promoter as a control. Luciferase activities were monitored by dual luciferase system. …

Gambogic Acid as a Candidate for Cancer Therapy: A Review.

Gambogic acid (GA), a kind of dry resin secreted by the Garcinia hanburyi tree, is a natural active ingredient with various biological activities, such as anti-cancer, anti-inflammatory, antioxidant, anti-bacterial effects, etc. An increasing amount of evidence indicates that GA has obvious anti-cancer effects via various molecular mechanisms, including the induction of apoptosis, autophagy, cell cycle arrest and the inhibition of invasion, metastasis, angiogenesis. In order to improve the efficacy in cancer treatment, nanometer drug delivery systems have been employed to load GA and form mice

Current cancer therapies and their influence on glucose control.

This review focuses on the development of hyperglycemia arising from widely used cancer therapies spanning four drug classes. These groups of medications were selected due to their significant association with new onset hyperglycemia, or of potentially severe clinical consequences when present. These classes include glucocorticoids that are frequently used in addition to chemotherapy treatments, and the antimetabolite class of 5-fluorouracil-related drugs. Both of these classes have been in use in cancer therapy since the 1950s. Also considered are the phosphatidyl inositol-3-kinase (PI3K)/AKT

Current and emerging therapeutic options in adrenocortical cancer treatment.

Adrenocortical carcinoma (ACC) is a very rare endocrine tumour, with variable prognosis, depending on tumour stage and time of diagnosis. The overall survival is five years from detection. Radical surgery is considered the therapy of choice in the first stages of ACC. However postoperative disease-free survival at 5 years is only around 30% and recurrence rates are frequent. o,p'DDD (ortho-, para'-, dichloro-, diphenyl-, dichloroethane, or mitotane), an adrenolytic drug with significant toxicity and unpredictable therapeutic response, is used in the treatment of ACC. Unfortunately, treatment f

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… The systemic administration of antisense oligonucleotides would represent an interesting approach for ACC therapy; moreover, an in vitro study demonstrated that a suicide vector, in which the herpes simplex virus thymidine kinase (HSV-TK) gene was driven by the CYP11B1 promoter with a P450scc enhancer …

Antidepressant Drug Sertraline against Human Cancer Cells.

The use of FDA-approved drugs for new indications represents a faster and more economical way to find novel therapeutic agents for cancer therapy, compared to the development of new drugs. Repurposing drugs is advantageous in a pharmacological context since these drugs already have extensive data related to their pharmacokinetics, facilitating their approval process for different diseases. Several studies have reported the promising anticancer effects of sertraline, both alone and combined, in different types of cancer cell lines. Here, we performed a literature review on the anticancer potent

Metformin-induced vitamin B12 deficiency: An underdiagnosed cause of diabetic neuropathy.

Metformin-induced vitamin B12 deficiency is a prevalent condition among patients with type 2 diabetes mellitus. In recent years, a growing body of evidence has demonstrated the association between vitamin B12 deficiency and the onset, progression, and worsening of diabetic neuropathy (DNP) as well as its improvement with supplementation in cases of deficiency. Major clinical guidelines for diabetes and DNP remain vague in their recommendations for B12 measurement and supplementation, and some guidelines do not address it at all. Given that vitamin B12 therapy is an economical, safe, and widely

The roles of curcumin in regulating the tumor immunosuppressive microenvironment.

Cancer is a harmful threat to human health. In addition to surgery, a variety of anticancer drugs are increasingly used in cancer therapy; however, despite the developments in multimodality treatment, the morbidity and mortality of patients with cancer patients are on the increase. The tumor-specific immunosuppressive microenvironment serves an important function in tumor tolerance and escape from immune surveillance leading to tumor progression. Therefore, identifying new drugs or foods that can enhance the tumor immune response is critical to develop improved cancer prevention methods and tr

Palbociclib regulates the expression of dihydrofolate reductase and the cell cycle to inhibit t (11;14) multiple myeloma.

BackgroundMultiple myeloma (MM) with t (11;14) has a unique biology. New combinations of novel agents are needed to improve the prognosis of patients with t (11;14) MM. As a selective inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), palbociclib (PAL) has been used to treat various malignancies, including breast cancer, ovarian cancer, and so on. However, the effects of PAL on MM remain unclear, and thus, further investigations are warranted.MethodsTwo t (11;14) MM cell lines, U266 and KMS27, were used in this study. The cell viability and cell cycle were detected to evaluate the anti-my

Clinical and Therapeutic Implications of Epstein-Barr Virus in HIV-Related Lymphomas.

The incidence of lymphomas is increased in people living with HIV (PLWH). Aggressive B-cell non-Hodgkin lymphomas (NHLs) are the most common and are considered an AIDS-defining cancer (ADC). Although Hodgkin lymphoma (HL) is not considered an ADC, its incidence is also increased in PLWH. Among all HIV-related lymphomas (HRL), the prevalence of Epstein-Barr virus (EBV) is high. It has been shown that EBV is involved in different lymphomagenic mechanisms mediated by some of its proteins, contributing to the development of different lymphoma subtypes. Additionally, cooperation between both HIV an

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… Unfortunately, latent EBV tumors do not express the EBV-thymidine kinase (TK), and for this reason, GCV may be ineffective. Thus, other strategies are focused on the induction of the EBV lytic cycle and EBV-TK [ 245 ]. …

A Review of New Findings in Adult T-cell Leukemia-Lymphoma: A Focus on Current and Emerging Treatment Strategies.

Adult T-cell leukemia-lymphoma (ATL), a rare and aggressive T-cell malignancy caused by human T-cell lymphotropic virus type 1 (HTLV-1), is associated with a poor prognosis. Evidence-based standard treatment options are lacking and outcomes are generally unsatisfactory, particularly for patients with relapsed or refractory disease. Continued research is contributing to changing treatment landscape as a number of existing and investigational agents are evaluated. We describe the epidemiology of HTLV-1 and ATL, discuss the biology behind the disease, review current treatment practices and guidel

Nanoparticle-Mediated Combination Therapy: Two-in-One Approach for Cancer.

Cancer represents a group of heterogeneous diseases characterized by uncontrolledgrowth and spread of abnormal cells, ultimately leading to death. Nanomedicine plays a significantrole in the development of nanodrugs, nanodevices, drug delivery systems and nanocarriers. Someof the major issues in the treatment of cancer are multidrug resistance (MDR), narrow therapeuticwindow and undesired side effects of available anticancer drugs and the limitations of anticancerdrugs. Several nanosystems being utilized for detection, diagnosis and treatment such as theranosticcarriers, liposomes, carbon nano

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… When ovarian and endometrial cancer cells were transfected with the herpes simplex virus thymidine kinase ( HSV-tk ) gene and treated with ganciclovir (GCV) using cationic liposomes, the antitumor effect of GCV was 47-640 times greater than when the same experiment was performed with a lacZ gene. … Herpes simplex virus thymidine kinase (HSV-TK)-loaded PEG-PBLG NPs are used to treat oral squamous cell carcinoma. …

Unlocking the Heterogeneity in Acute Leukaemia: Dissection of Clonal Architecture and Metabolic Properties for Clinical Interventions.

Genetic studies of haematological cancers have pointed out the heterogeneity of leukaemia in its different subpopulations, with distinct mutations and characteristics, impacting the treatment response. Next-generation sequencing (NGS) and genome-wide analyses, as well as single-cell technologies, have offered unprecedented insights into the clonal heterogeneity within the same tumour. A key component of this heterogeneity that remains unexplored is the intracellular metabolome, a dynamic network that determines cell functions, signalling, epigenome regulation, immunity and inflammation. Unders

Targeted and epigenetic therapies for acute myeloid leukemia treatment.

This article provides a comprehensive overview of targeted and epigenetic therapies for acute myeloid leukemia (AML), highlighting their role in advancing treatment strategies. Recognizing that AML arises from complex genetic and epigenetic alterations, a deeper understanding of its pathogenesis has paved the way for precision medicine. The article reviews key targeted therapies, including IDH inhibitors (e.g., ivosidenib, enasidenib) for IDH mutations, FLT3 inhibitors (e.g., midostaurin, gilteritinib) for FLT3 alterations, BCL2 inhibitors (e.g., venetoclax) impacting apoptosis, and emerging M

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… The therapeutic transgenes’ repertoire in targeting malignant cells spans genes encoding cytotoxic, pro-apoptotic, antiproliferative proteins alongside conventional suicide genes like the herpes simplex virus thymidine kinase gene. …