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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

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… Elevation of polyamine levels results in enhanced tumorigenesis in Saccharomyces cerevisiae , pancreatic adenocarcinoma, neuroendocrine tumors, and breast cancer [ 59 , 60 , 61 ]. …

Recent Advances in Understanding the Mechanisms of Elemene in Reversing Drug Resistance in Tumor Cells: A Review.

Malignant tumors are life-threatening, and chemotherapy is one of the common treatment methods. However, there are often many factors that contribute to the failure of chemotherapy. The multidrug resistance of cancer cells during chemotherapy has been reported, since tumor cells' sensitivity decreases over time. To overcome these problems, extensive studies have been conducted to reverse drug resistance in tumor cells. Elemene, an extract of the natural drug Curcuma wenyujin, has been found to reverse drug resistance and sensitize cancer cells to chemotherapy. Mechanisms by which elemene rever

Application and mechanistic research of novel therapeutic strategies in cisplatin-resistant small cell lung cancer.

IntroductionSmall cell lung cancer (SCLC) initially responds well to cisplatin-based chemotherapy, but rapid development of drug resistance limits long-term efficacy and subsequent treatment options. Understanding the multifactorial mechanisms of cisplatin resistance is essential for improving patient outcomes. This review synthesizes recent preclinical and clinical advances, focusing on seven key resistance mechanisms and emerging therapeutic strategies, including immunotherapy, targeted therapy, and novel chemotherapeutic agents.DiscussionCisplatin resistance in SCLC arises through multiple

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… The copper transporter CTR1 regulates cisplatin uptake in Saccharomyces cerevisiae . Mol Pharmacol . 2002 ; 62 ( 5 ): 1154 – 1159 . doi: 10.1124/mol.62.5.1154 . 12391279 28 Ishida S , Lee J , Thiele DJ , et al. …

Postbiotics as Emerging Strategy Targeting Obesity- and Aging-Related Breast Cancer-Prospects in Prophylaxis and Therapy.

Aging and obesity accompanied with hormonal disequilibrium represent critical, inter-related risk factors for breast cancer, significantly influencing disease incidence, progression, and therapeutic outcomes. This review aims to elucidate the multifaceted biological mechanisms linking obesity and aging to breast carcinogenesis, with a particular focus on the emerging therapeutic and preventive potential of postbiotics as molecules targeting cellular events important for cancer growth and responsiveness. Despite continuous advancement, breast cancer therapy still poses several challenges, such

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… In one clinical trial involving women with breast cancer undergoing chemotherapy, oral administration of β-glucan derived from Saccharomyces cerevisiae combined with Lactobacillus rhamnosus GG resulted in a slight increase in IL-12 levels and a significant reduction in serum IL-4 levels in the intervention …

HDACs and Their Inhibitors on Post-Translational Modifications: The Regulation of Cardiovascular Disease.

Cardiovascular diseases (CVD), such as myocardial hypertrophy, heart failure, atherosclerosis, and myocardial ischemia/reperfusion (I/R) injury, are among the major threats to human health worldwide. Post-translational modifications alter the function of proteins through dynamic chemical modification after synthesis. This mechanism not only plays an important role in maintaining homeostasis and plays a crucial role in maintaining normal cardiovascular function, but is also closely related to the pathological state of various diseases. Histone deacetylases (HDACs) play an important role in the

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… A suppressor of mating-type locus mutations in Saccharomyces cerevisiae: Evidence for and identification of cryptic mating-type loci. Genetics. 1979;93:877–901. doi: 10.1093/genetics/93.4.877. 27. Tanno M., Sakamoto J., Miura T., Shimamoto K., Horio Y. …

Targeting histone deacetylases in head and neck squamous cell carcinoma: molecular mechanisms and therapeutic targets.

The onerous health and economic burden associated with head and neck squamous cell carcinoma (HNSCC) is a global predicament. Despite the advent of novel surgical techniques and therapeutic protocols, there is an incessant need for efficacious diagnostic and therapeutic targets to monitor the invasion, metastasis and recurrence of HNSCC due to its substantial morbidity and mortality. The differential expression patterns of histone deacetylases (HDACs), a group of enzymes responsible for modifying histones and regulating gene expression, have been demonstrated in neoplastic tissues. However, th

Gut microbiota shapes cancer immunotherapy responses.

The gut microbiota significantly influences cancer immunotherapy efficacy by modulating immune responses, remodeling the tumor microenvironment (TME), and producing key metabolites. Strategies such as FMT, probiotics, and dietary interventions show promise in enhancing responses to ICIs and ACTs while reducing immune-related adverse events (irAEs). This review summarizes clinical and preclinical findings and discusses microbiota-based interventions and future directions for precision immunotherapy.

10th Trends in Medical Mycology Held on 8 to 11 October 2021, Aberdeen, Scotland, Organized by the European Confederation of Medical Mycology (ECMM).

Plenary Sessions: [...].

Unlocking the potential of tumor-targeting peptides in precision oncology.

Targeted cancer therapy has emerged as a promising alternative to conventional chemotherapy, which is often plagued by poor selectivity, off-target effects, and drug resistance. Among the various targeting agents in development, peptides stand out for their unique advantages, including minimal immunogenicity, high tissue penetration, and ease of modification. Their small size, specificity, and flexibility allow them to target cancer cells while minimizing damage to healthy tissue selectively. Peptide-based therapies have shown great potential in enhancing the efficacy of drug delivery, improvi

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… The system typically involves the fusion of a peptide library to a scaffold protein, such as the Aga2p subunit of the Aga1p–Aga2p adhesion complex in Saccharomyces cerevisiae [ 39 ]. This allows peptides to be displayed on the yeast surface while maintaining proper folding and functionality. …

Human microbiomes in cancer development and therapy.

Colonies formed by bacteria, archaea, fungi, and viral groups and their genomes, metabolites, and expressed proteins constitute complex human microbiomes. An increasing evidences showed that carcinogenesis and disease progression were link to microbiomes. Different organ sources, their microbial species, and their metabolites are different; the mechanisms of carcinogenic or procancerous are also different. Here, we summarize how microbiomes contribute to carcinogenesis and disease progression in cancers of the skin, mouth, esophagus, lung, gastrointestinal, genital, blood, and lymph malignancy

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… Recent advances in the application of probiotic yeasts, particularly Saccharomyces, as an adjuvant therapy in the management of cancer with focus on colorectal cancer. Mol Biol Rep. 2021;48(1):951‐960. 30. Gur C, Ibrahim Y, Isaacson B, et al. …

Reactive Oxygen Species Bridge the Gap between Chronic Inflammation and Tumor Development.

According to numerous animal studies, adverse environmental stimuli, including physical, chemical, and biological factors, can cause low-grade chronic inflammation and subsequent tumor development. Human epidemiological evidence has confirmed the close relationship between chronic inflammation and tumorigenesis. However, the mechanisms driving the development of persistent inflammation toward tumorigenesis remain unclear. In this study, we assess the potential role of reactive oxygen species (ROS) and associated mechanisms in modulating inflammation-induced tumorigenesis. Recent reports have e

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… Sml1 inhibits the DNA repair activity of Rev1 in Saccharomyces cerevisiae during oxidative stress. Applied and Environmental Microbiology . 2020;86(7) doi: 10.1128/AEM.02838-19. 175. Laval F., Wink D. A., Laval J. …

Resveratrol: Molecular Mechanisms, Health Benefits, and Potential Adverse Effects.

Resveratrol (RES), a naturally occurring polyphenolic compound, has garnered significant attention due to its diverse biological activities, which include anti-inflammatory, antioxidant, and antiaging properties. This review synthesizes current evidence concerning the molecular mechanisms, therapeutic efficacy, and safety profile of RES across a variety of pathologies, with an emphasis on the latest research conducted in recent years. Mechanistically, RES is known to modulate critical signaling pathways such as the activation of sirtuin 1. These actions collectively contribute to the attenuati

Application of toll-like receptors (TLRs) and their agonists in cancer vaccines and immunotherapy.

Toll-like receptors (TLRs) are pattern recognition receptors (PRRs) expressed in various immune cell types and perform multiple purposes and duties involved in the induction of innate and adaptive immunity. Their capability to propagate immunity makes them attractive targets for the expansion of numerous immunotherapeutic approaches targeting cancer. These immunotherapeutic strategies include using TLR ligands/agonists as monotherapy or combined therapeutic strategies. Several TLR agonists have demonstrated significant efficacy in advanced clinical trials. In recent years, multiple reports est

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… Mannan, a branched polysaccharide from the yeast Saccharomyces cerevisiae , is affixed to the cancer cell membranes through linkage with the hydrophobic BAM (Biocompatible Anchor for Membrane) anchor and serves as a PAMP, which in turn is recognized by the mannan-binding lectin complex (MBL) ( 11 , 14 …

Direct Endoplasmic Reticulum Targeting by the Selective Alkylphospholipid Analog and Antitumor Ether Lipid Edelfosine as a Therapeutic Approach in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC), the most common malignancy of the pancreas, shows a dismal and grim overall prognosis and survival rate, which have remained virtually unchanged for over half a century. PDAC is the most lethal of all cancers, with the highest mortality-to-incidence ratio. PDAC responds poorly to current therapies and remains an incurable malignancy. Therefore, novel therapeutic targets and drugs are urgently needed for pancreatic cancer treatment. Selective induction of apoptosis in cancer cells is an appealing approach in cancer therapy. Apoptotic cell death is highly

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… In an attempt to unveil the molecular mechanism of the antitumor ether lipid edelfosine, we used the budding yeast Saccharomyces cerevisiae —which is sensitive to the cytotoxic action of edelfosine [ 197 , 199 , 200 , 212 ]—as an experimental eukaryotic model organism [ 213 ]. …

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

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… Saccharomyces cerevisiae (Baker's Yeast) as an interfering RNA expression and delivery system. Curr. Drug Targets 20, 942–952. 10.2174/1389450120666181126123538 Ettl J. (2019). Management of adverse events due to cyclin-dependent kinase 4/6 inhibitors. BRC 14, 86–92. 10.1159/000499534 Faller W. …

CRISPR-Cas9 Therapeutics in Early Clinical Development: Delivery and Molecular Diagnostics.

CRISPR-Cas9 has progressed from an experimental tool to a therapeutic modality, marked by the first regulatory approvals of an ex vivo-edited autologous CD34+ hematopoietic stem cell product that induces fetal hemoglobin (CASGEVY/exa-cel). In this narrative review, we synthesize modality-specific molecular diagnostic strategies used across early CRISPR clinical translation. In parallel, early clinical experience has begun to demonstrate the feasibility of in vivo editing, including subretinal delivery for CEP290-associated inherited retinal degeneration (EDIT-101 programme) and hepatocyte-targ

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… A gRNA-tRNA array for CRISPR-Cas9 based rapid multiplexed genome editing in Saccharomyces cerevisiae Nat. Commun. 2019 10 1053 10.1038/s41467-019-09005-3 30837474 PMC6400946 52. Yi J.Y. Kim M. Ahn J.H. Kim B.G. Son J. Sung C. …

Insights into the role of RNA m6A modification in the metabolic process and related diseases.

According to the latest consensus, many traditional diseases are considered metabolic diseases, such as cancer, type 2 diabetes, obesity, and cardiovascular disease. Currently, metabolic diseases are increasingly prevalent because of the ever-improving living standards and have become the leading threat to human health. Multiple therapy methods have been applied to treat these diseases, which improves the quality of life of many patients, but the overall effect is still unsatisfactory. Therefore, intensive research on the metabolic process and the pathogenesis of metabolic diseases is imperati

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… Induction of sporulation in Saccharomyces cerevisiae leads to the formation of N6-methyladenosine in mRNA: a potential mechanism for the activity of the IME4 gene Nucleic Acids Res 30 20 2002 4509 4518 12384598 10.1093/nar/gkf573 PMC137137 12 Jia G. Fu Y. He C. …

Stochasticity of anticancer mechanisms underlying clinical effectiveness of vorinostat.

The Food and Drug Administration (FDA) has approved vorinostat, also called Zolinza®, for its effectiveness in fighting cancer. This drug is a suberoyl-anilide hydroxamic acid belonging to the class of histone deacetylase inhibitors (HDACis). Its HDAC inhibitory potential allows it to accumulate acetylated histones. This, in turn, can restore normal gene expression in cancer cells and activate multiple signaling pathways. Experiments have proven that vorinostat induces histone acetylation and cytotoxicity in many cancer cell lines, increases the level of p21 cell cycle proteins, and enhances p

The Impact of Human Microbiotas in Hematopoietic Stem Cell and Organ Transplantation.

The human microbiota heavily influences most vital aspects of human physiology including organ transplantation outcomes and transplant rejection risk. A variety of organ transplantation scenarios such as lung and heart transplantation as well as hematopoietic stem cell transplantation is heavily influenced by the human microbiotas. The human microbiota refers to a rich, diverse, and complex ecosystem of bacteria, fungi, archaea, helminths, protozoans, parasites, and viruses. Research accumulating over the past decade has established the existence of complex cross-species, cross-kingdom interac

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… Another study analyzing the blood cultures of 3,796 HSCT recipients for signs of bloodstream infections occurring within 1 year of the procedure caused by common probiotic organisms such as Lactobacillus species, Bifidobacterium species, Streptococcus species, and Saccharomyces species, found only 0.5% …

High-Dose Vitamin C for Cancer Therapy.

In recent years, the idea that Vitamin C (Vit-C) could be utilized as a form of anti-cancer therapy has generated many contradictory arguments. Recent insights into the physiological characteristics of Vit-C, its pharmacokinetics, and results from preclinical reports, however, suggest that high-dose Vit-C could be effectively utilized in the management of various tumor types. Studies have shown that the pharmacological action of Vit-C can attack various processes that cancerous cells use for their growth and development. Here, we discuss the anti-cancer functions of Vit-C, but also the potenti

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… Cadmium-induced oxidative stress in Saccharomyces cerevisiae. Indian J. Biochem. Biophys. 2010;47:383–387. 56. Tominaga H., Kodama S., Matsuda N., Suzuki K., Watanabe M. Involvement of reactive oxygen species (ROS) in the induction of genetic instability by radiation. J. Radiat. …