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What's your poison? Impact of individual repair capacity on the outcomes of genotoxic therapies in cancer. Part II - information content and validity of biomarkers for individual repair capacity in the assessment of outcomes of anticancer therapy.

The individual variance in the efficiency of repair of damage induced by genotoxic therapies may be an important factor in the assessment of eligibility for different anticancer treatments, the outcomes of various treatments and the therapy-associated complications, including acute and delayed toxicity and acquired drug resistance. The second part of this paper analyses the currently available information about the possibilities of using experimentally obtained knowledge about individual repair capacity for the purposes of personalised medicine and healthcare.

Transplant oncology and anti-cancer immunosuppressants.

Organ transplantation is a life-saving intervention that enhances the quality of life for patients with end-stage organ failure. However, long-term immunosuppressive therapy is required to prevent allogeneic graft rejection, which inadvertently elevates the risk of post-transplant malignancies, especially for liver transplant recipients with a prior history of liver cancer. In response, the emerging field of transplant oncology integrates principles from oncology and immunology to improve outcomes for patients at high risk of tumor occurrence or recurrence following transplantation. Therefore,

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… This inhibition disrupts the transfer of one carbon units during the biosynthesis of purine and pyrimidine nucleotides, ultimately leading to the inhibition of DNA synthesis. …

Transcription and Translation Inhibitors in Cancer Treatment.

Transcription and translation are fundamental cellular processes that govern the protein production of cells. These processes are generally up regulated in cancer cells, to maintain the enhanced metabolism and proliferative state of these cells. As such cancerous cells can be susceptible to transcription and translation inhibitors. There are numerous druggable proteins involved in transcription and translation which make lucrative targets for cancer drug development. In addition to proteins, recent years have shown that the "undruggable" transcription factors and RNA molecules can also be targ

Recent Insights into the Creation of Histone Deacetylase Inhibitors for the Treatment of Human Diseases.

This review examines publications over the past two years devoted to histone deacetylase inhibitors for the treatment of cancer, diseases of the nervous, cardiovascular, digestive, and respiratory systems, and autoimmune diseases. The review covers various classes of histone deacetylase inhibitors depending on the zinc-binding group, in particular hydroxamic acids, benzamides, hydrazides, carboxylic acids, and cyclic peptides. The review pays special attention to the mechanisms of development of pathologies involving various isoforms of histone deacetylases. The review shows that, for the trea

Ocular complications of antineoplastic therapies.

Ocular complications of antineoplastic agents can have a profound effect on the quality of life of cancer patients. New oncologic treatments like monoclonal antibodies, immunotherapies, antibody-drug conjugates, checkpoint inhibitors and growth factor receptors have resulted in increased ocular complications. These ocular complications differs in respect to distinct mechanisms of actions and lead to significant challenges in the management of cancer patients. In this review, we reviewed literature, clinical studies and cases detailing ocular complications due to administration of antineoplasti

Chemistry and Pharmacology of Fluorinated Drugs Approved by the FDA (2016-2022).

Fluorine is characterized by high electronegativity and small atomic size, which provide this molecule with the unique property of augmenting the potency, selectivity, metabolic stability, and pharmacokinetics of drugs. Fluorine (F) substitution has been extensively explored in drug research as a means of improving biological activity and enhancing chemical or metabolic stability. Selective F substitution onto a therapeutic or diagnostic drug candidate can enhance several pharmacokinetic and physicochemical properties such as metabolic stability and membrane permeation. The increased binding a

Vincristine-Induced Peripheral Neuropathy in Childhood Acute Lymphoblastic Leukemia: Genetic Variation as a Potential Risk Factor.

Vincristine (VCR) is the first-line chemotherapeutic medication often co-administered with other drugs to treat childhood acute lymphoblastic leukemia. Dose-dependent neurotoxicity is the main factor restricting VCR's clinical application. VCR-induced peripheral neuropathy (VIPN) sometimes results in dose reduction or omission, leading to clinical complications or affecting the patient's quality of life. With regard to the genetic basis of drug responses, preemptive pharmacogenomic testing and simultaneous blood level monitoring could be helpful for the transformation of various findings into

Phosphodiesterase 7: a potential novel therapeutic target in ovarian cancer.

INTRODUCTION: Chemoresistance and disease relapses in epithelial ovarian cancer (EOC) highlight the need for novel therapeutic strategies. Here, we investigated phosphodiesterase 7A (PDE7A) as a potential target in ovarian cancer treatment. METHODS: Gene expression was performed by RNA sequencing data comparing high-grade serous ovarian carcinoma (HGSOC) and fallopian tube samples. The PDE7 inhibitor BRL 50481, alone or combined with paclitaxel (PTX), was tested in drug-sensitive A2780 and multi-resistant OVCAR3 cells by Diphenyltetrazolium bromide (MTT) assay. To validate data from the high

Glutamine and cancer: metabolism, immune microenvironment, and therapeutic targets.

Glutamine is the most abundant amino acid in human serum, and it can provide carbon and nitrogen for biosynthesis, which is crucial for proliferating cells. Moreover, it is widely known that glutamine metabolism is reprogrammed in cancer cells. Many cancer cells undergo metabolic reprogramming targeting glutamine, increasing its uptake to meet their rapid proliferation demands. An increasing amount of study is being done on the particular glutamine metabolic pathways in cancer cells.Further investigation into the function of glutamine in immune cells is warranted given the critical role these

FDA-Approved Drugs for Hematological Malignancies-The Last Decade Review.

Hematological malignancies, also referred to as blood cancers, are a group of diseases involving abnormal cell growth and persisting in the blood, lymph nodes, or bone marrow. The development of new targeted therapies including small molecule inhibitors, monoclonal antibodies, bispecific T cell engagers, antibody-drug conjugates, recombinant immunotoxins, and, finally, Chimeric Antigen Receptor T (CAR-T) cells has improved the clinical outcomes for blood cancers. In this review, we summarized 52 drugs that were divided into small molecule and macromolecule agents, approved by the Food and Drug

Оценка причинно-следственного воздействия метаболомы на риск психических и нейродегенеративных расстройств.

Данные свидетельствуют о фенотипическом и биологическом переплетении между психическими и нейродегенеративными расстройствами. Дальнейшее выявление лежащих в основе взаимных и уникальных биологических механизмов может привести к появлению новых, многопорядковых и многопорядковых терапевтических целей. Метаболом представляет собой важную область для идентификации целей, поскольку метаболиты играют важнейшую роль в модуляции разнообразных биологических процессов.Мы использовали менделианскую случайность (MR) для проверки причинного воздействия ~ 1000 плазменных метаболитов и ~ 300 метаболитов на

A dual-mechanism model of Selinexor in DLBCL: p53 reactivation and metabolic reprogramming.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy with limited therapeutic options in the relapsed or refractory setting. Selinexor, a selective inhibitor of nuclear export targeting XPO1, has demonstrated clinical activity in DLBCL. However, the molecular mechanisms underlying its antitumor effects remain incompletely defined. METHODS: We evaluated the clinical efficacy of Selinexor in a real-world cohort of lymphoma patients and performed integrative transcriptomic and proteomic analyses in DLBCL cell models representing germinal center B-cell–like (GCB) and non-G

Molecular Inhibitors of Growth Signals

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Chemotherapy Side-Effects: Not All DNA Damage Is Equal.

Recent advances have increased survival rates of children and adults suffering from cancer thanks to effective anti-cancer therapy, such as chemotherapy. However, during treatment and later in life they are frequently confronted with the severe negative side-effects of their life-saving treatment. The occurrence of numerous features of accelerated aging, seriously affecting quality of life, has now become one of the most pressing problems associated with (pediatric) cancer treatment. Chemotherapies frequently target and damage the DNA, causing mutations or genome instability, a major hallmark

Modulating epigenetic modifications for cancer therapy (Review).

Cancer is a global public health concern. Alterations in epigenetic processes are among the earliest genomic aberrations occurring during cancer development and are closely related to progression. Unlike genetic mutations, aberrations in epigenetic processes are reversible, which opens the possibility for novel pharmacological treatments. Non‑coding RNAs (ncRNAs) represent an essential epigenetic mechanism, and emerging evidence links ncRNAs to carcinogenesis. Epigenetic drugs (epidrugs) are a group of promising target therapies for cancer treatment acting as coadjuvants to reverse drug resist

Therapeutic Potential of Chlorogenic Acid in Chemoresistance and Chemoprotection in Cancer Treatment.

Chemotherapeutic drugs are indispensable in cancer treatment, but their effectiveness is often lessened because of non-selective toxicity to healthy tissues, which triggers inflammatory pathways that are harmful to vital organs. In addition, tumors' resistance to drugs causes failures in treatment. Chlorogenic acid (5-caffeoylquinic acid, CGA), found in plants and vegetables, is promising in anticancer mechanisms. In vitro and animal studies have indicated that CGA can overcome resistance to conventional chemotherapeutics and alleviate chemotherapy-induced toxicity by scavenging free radicals

Clinical Treatment Study of Secondary Multiple Squamous Cell Carcinoma with Psoriasis Vulgaris.

Dermatologic diseases are the fourth most frequent nonfatal common illness, yet they have a psychological, economical, and professional burden that is comparable to or larger than other chronic conditions. From a survey in China of 6 provinces, the overall prevalence of psoriasis with squamous cell carcinoma was 0.47%. According to the current investigation, the outburst of skin disease was not associated with gender, but mainly with the climate of the environment; that is, dry cold weather will more likely to induce psoriasis. Approximately 3% of people around the world have psoriasis, which

MTAP-Null Tumors: A Comprehensive Review on Synthetic Vulnerabilities and Therapeutic Strategies.

Homozygous deletion of the 9p21.3 genomic locus spanning the CDKN2A/B and MTAP genes is an event affecting 15% of cancers. While CDKN2A is a well-established tumor suppressor gene, the role of MTAP in tumorigenesis varies across cancer types. MTAP codes for methylthioadenosine phosphorylase, a key enzyme in the methionine salvage pathway, and its loss has been associated with several downstream synthetic vulnerabilities. Despite multiple efforts to exploit MTAP loss for targeted therapies, none of these efforts have yielded substantial results in clinical trials. In this review, we consolidate

Microbiome and pancreatic cancer: time to think about chemotherapy.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer characterized by late diagnosis, rapid progression, and a high mortality rate. Its complex biology, characterized by a dense, stromal tumor environment with an immunosuppressive milieu, contributes to resistance against standard treatments like chemotherapy and radiation. This comprehensive review explores the dynamic role of the microbiome in modulating chemotherapy efficacy and outcomes in PDAC. It delves into the microbiome's impact on drug metabolism and resistance, and the interaction between microbial elements, drugs,

Читинас-3-подобный-1: многообразный игрок в нейроинфламмации и дегенеративной патологии с терапевтическими последствиями.

Читинас-3-подобный-1 (CHI3L1) — эволюционно сохранившийся белок, содержащийся в ключевых биологических процессах, включая реконструирование тканей, ангиогенез и нейроинфламмацию. Она стала важным игроком в различных нейродегенеративных заболеваниях и расстройствах мозга. Повышенные уровни CHI3L1 наблюдались в таких неврологических условиях, как травматическое повреждение мозга (TBI), болезнь Альцгеймера (AD), болезнь Паркинсона (PD), амиотропический боковой склероз (ALS), болезнь Креуцфельда-Якоба (CJD), множественный склероз (MS), оптика нейромиелита (NMO), вызванная ВИЧ деменция (HAD), цереб