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TP53-mutated myelodysplastic syndromes and acute myeloid leukemia: a comprehensive overview of targeted approaches.

TP53-mutated acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) represent a biologically and clinically distinct subset of myeloid malignancies characterized by poor prognosis, resistance to standard therapies, and high rates of relapse. TP53 mutations, particularly biallelic are frequently associated with complex karyotypes and confer profound chemoresistance. Although hypomethylating agents and venetoclax-based combinations provide modest benefit, durable remissions remain rare. Novel therapeutic strategies targeting mutant p53, restoring wild-type function, or exploiting synth

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… Further mechanistic studies using AML cell-line models demonstrated that ATO also induces ferroptotic cell death in TP53-mutant cells by depleting glutathione peroxidase 4 (GPX4) and the cystine transporter SLC7A11 ( 182 ). …

Extracellular vesicles in multiple myeloma-bone marrow niche crosstalk: from cellular dialogue to clinical perspectives.

Multiple myeloma (MM) is a haematological neoplasia defined by the clonal expansion of malignant plasma cells within the intricate and dynamic ecosystem of the bone marrow (BM). Although genetic aberrations intrinsic to tumour cells play a critical role in MM initiation, the advancement and aggressiveness of the disease are heavily influenced by ongoing signalling exchanges and persistent interactions with the surrounding microenvironment. Extracellular vesicles (EVs) are increasingly recognized as essential messengers in this reciprocal communication, acting as membrane-encapsulated vehicles

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… Moreover, it was found that targeting the cystine/glutamate antiporter System Xc − disrupts exosome-mediated crosstalk between BM MSCs and MM cells, reversing Bortezomib resistance [ 116 ]. Several studies have investigated the contribution of specific BM subpopulations in PI resistance. …

Antibody-Drug Conjugates: Ushering in a New Era of Cancer Therapy.

Antibody-drug conjugates (ADCs) have provided new therapeutic options and significant promise for patients with cancer, particularly where existing treatments are limited. Substantial effort in ADC development is underway globally, with 13 ADCs currently approved and many more in development. The therapeutic benefits of ADCs leverage the ability to selectively target cancer cells through antibody binding, resultant relative sparing of non-malignant tissues, and the targeted delivery of a cytotoxic payload. Consequently, this drug class has demonstrated activity in multiple malignancies refract

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… ADCs produced using enzymatic conjugation to the light chain or position Q295 on the antibody had superior pharmacokinetic behaviour, as did those engineered with cystine conjugation to the L328 position [ 29 ]. …

Promising Activities of Marine Natural Products against Hematopoietic Malignancies.

According to the WHO classification of tumors, more than 150 typologies of hematopoietic and lymphoid tumors exist, and most of them remain incurable diseases that require innovative approaches to improve therapeutic outcome and avoid side effects. Marine organisms represent a reservoir of novel bioactive metabolites, but they are still less studied compared to their terrestrial counterparts. This review is focused on marine natural products with anticancer activity against hematological tumors, highlighting recent advances and possible perspectives. Until now, there are five commercially avai

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… New Cyclic Cystine Bridged Peptides from the Sponge Suberites Waedoensis. Mar. Drugs. 2014;12:2760–2770. doi: 10.3390/md12052760. 91. Kim C.-K., Song I.-H., Park H.Y., Lee Y.-J., Lee H.-S., Sim C.J., Oh D.-C., Oh K.-B., Shin J. …

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Vitamin C Supplementation in the Treatment of Autoimmune and Onco-Hematological Diseases: From Prophylaxis to Adjuvant Therapy.

Vitamin C is a water-soluble vitamin introduced through the diet with anti-inflammatory, immunoregulatory, and antioxidant activities. Today, this vitamin is integrated into the treatment of many inflammatory pathologies. However, there is increasing evidence of possible use in treating autoimmune and neoplastic diseases. We reviewed the literature to delve deeper into the rationale for using vitamin C in treating this type of pathology. There is much evidence in the literature regarding the beneficial effects of vitamin C supplementation for treating autoimmune diseases such as Systemic Lupus

Vascular endothelial growth factor signaling in health and disease: from molecular mechanisms to therapeutic perspectives.

Vascular endothelial growth factor (VEGF) signaling is a critical regulator of vasculogenesis, angiogenesis, and lymphangiogenesis, processes that are vital for the development of vascular and lymphatic systems, tissue repair, and the maintenance of homeostasis. VEGF ligands and their receptors orchestrate endothelial cell proliferation, migration, and survival, playing a pivotal role in dynamic vascular remodeling. Dysregulated VEGF signaling drives diverse pathological conditions, including tumor angiogenesis, cardiovascular diseases, and ocular disorders. Excessive VEGF activity promotes tu

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… Structural diversity of VEGF family members with their receptors The VEGF family, comprising VEGF-A, VEGF-B, VEGF-C, and VEGF-D, regulates vascular and lymphatic development through isoforms generated by alternative splicing 20 or proteolytic cleavage. 21 These proteins share a cystine-knot motif critical …

Cancer-Associated Fibroblasts: Heterogeneity, Cancer Pathogenesis, and Therapeutic Targets.

Cancer-associated fibroblasts (CAFs) are functionally diverse stromal regulators that orchestrate tumor progression, metastasis, and therapy resistance through dynamic crosstalk within the tumor microenvironment (TME). Recent advances in single-cell multiomics and spatial transcriptomics have identified conserved CAF subtypes with distinct molecular signatures, spatial distributions, and context-dependent roles, highlighting their dual capacity to promote immunosuppression or restrain tumor growth. However, therapeutic strategies struggle to reconcile this functional duality, hindering clinica

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… Kimura et al. [ 364 ] developed and validated a novel engineered cystine knot peptide (knottin) that selectively binds to human integrin αvβ6 with sub‐nanomolar affinity. …

Targeting strategies for bone diseases: signaling pathways and clinical studies.

Since the proposal of Paul Ehrlich's magic bullet concept over 100 years ago, tremendous advances have occurred in targeted therapy. From the initial selective antibody, antitoxin to targeted drug delivery that emerged in the past decades, more precise therapeutic efficacy is realized in specific pathological sites of clinical diseases. As a highly pyknotic mineralized tissue with lessened blood flow, bone is characterized by a complex remodeling and homeostatic regulation mechanism, which makes drug therapy for skeletal diseases more challenging than other tissues. Bone-targeted therapy has b

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… been well-recognized since the approval of romosozumab, no effective measures were identified until a recent report by Yu and Wang et al. that targeting loop3 of sclerostin may attenuate cardiovascular risk while retaining its skeletal protection. 140 Structurally, sclerostin is composed of a core cystine …

Anti-Cancer Stem-like Cell Compounds in Clinical Development - An Overview and Critical Appraisal.

Cancer stem-like cells (CSC) represent a subpopulation of tumor cells with elevated tumor-initiating potential. Upon differentiation, they replenish the bulk of the tumor cell population. Enhanced tumor-forming capacity, resistance to antitumor drugs, and metastasis-forming potential are the hallmark traits of CSCs. Given these properties, it is not surprising that CSCs have become a therapeutic target of prime interest in drug discovery. In fact, over the last few years, an enormous number of articles describing compounds endowed with anti-CSC activities have been published. In the meanwhile,

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… In another study, xCT, the functional subunit of the cystine/glutamate antiporter system xc-, has been found to be upregulated in mammospheres derived from murine human EGFR2-positive breast tumor cells ( 190 ). …

The Role of the CCR5 Receptor in Neuropathic Pain Modulation: Current Insights and Therapeutic Implications.

Neuropathic pain, a chronic condition arising from injury or dysfunction of the somatosensory nervous system, is characterized by persistent hypersensitivity and spontaneous pain. The chemokine receptor CCR5 (C-C motif chemokine receptor 5) has recently been identified as a critical mediator in neuroinflammation and neuropathic pain signaling pathways. Expressed on immune cells and neurons, CCR5 regulates immune cell recruitment and activation, thereby contributing to neuronal sensitization and maintenance of pain states. This review examines the currently characterized molecular mechanisms th

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… receptor potential melastatin 8 TRPV1 | Transient receptor potential vanilloid 1 V1 | Variable region 1 of gp120 V2 | Variable region 2 of gp120 V3 | Variable region 3 of gp120 VEGF | Vascular endothelial growth factor VGCC | Voltage-gated calcium channel VGSC | Voltage-gated sodium channel Xc − | Cystine …

Targeting SREBP-2-Regulated Mevalonate Metabolism for Cancer Therapy.

Recently, targeting metabolic reprogramming has emerged as a potential therapeutic approach for fighting cancer. Sterol regulatory element binding protein-2 (SREBP-2), a basic helix-loop-helix leucine zipper transcription factor, mainly regulates genes involved in cholesterol biosynthesis and homeostasis. SREBP-2 binds to the sterol regulatory elements (SREs) in the promoters of its target genes and activates the transcription of mevalonate pathway genes, such as HMG-CoA reductase (HMGCR), mevalonate kinase and other key enzymes. In this review, we first summarized the structure of SREBP-2 and

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… HMGCR HMGCR | Endometrial carcinoma Pancreatic and Prostate cancer | Synergistically inhibits growth and induces apoptosis by upregulating AMPK phosphorylation and downregulating S6 phosphorylation ( 175 ) Synergize to accumulate ROS production and cause apoptosis by targeting the compensatory xCT cystine …

Immune Checkpoint Inhibitors and Immunomodulators for Cancer Immunotherapy: Insights Into Resistance and Therapeutic Strategies.

Cancer immunotherapy has redefined cancer treatment. However, the molecular and cellular basis of immune evasion and therapeutic resistance remains incompletely understood. Early immune checkpoint inhibitors have delivered significant clinical benefit, but their efficacy and durability remain limited in many patients. These limitations have driven the exploration of next-generation immune checkpoints and additional regulatory pathways that shape tumor-immune interactions. Recent advances have broadened the immune checkpoint landscape and revealed new targets. These targets operate within inter

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… On one hand, IFNG secreted by activated immune cells such as T cells can downregulate cystine/glutamate antiporter system xc − (SLC3A2 and SLC7A11) expression or upregulate acyl‐CoA synthetase long‐chain family member 4 (ACSL4) in tumor cells. …

Xanthohumol: Mechanistic Actions and Emerging Evidence as a Multi-Target Natural Nutraceutical.

BACKGROUND: Xanthohumol (XN), a prenylated chalcone flavonoid derived from hops (Humulus lupulus), is increasingly recognized as a highly pleiotropic natural compound. OBJECTIVE: We aimed to structure XN's mechanistic hierarchy with emerging translational relevance across disease areas. METHODS: We performed a comprehensive and integrative literature review of XN for its biological and translational effects across cancer, metabolic, neurological, cardiovascular, hepatic, renal, and dermatological disorders. RESULTS: Mechanistically, XN exerts diverse bioactivities by inhibiting major pro-on

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… XN further stabilized glutathione disulfide and cystine redox potentials, supporting its role in antioxidant defense [ 63 ]. Alzheimer’s Disease (AD) Models: XN demonstrates broad and consistent neuroprotective activity across multiple AD cellular and animal models. …

E3 ubiquitin ligases orchestrate chemo-resistance in gastrointestinal malignancies: from DNA damage response to therapeutic targeting.

Therapy resistance in gastrointestinal tumors remains a critical challenge in clinical oncology, severely compromising therapeutic efficacy and long-term patient survival. E3 ubiquitin ligases, as core enzymes involved in the protein ubiquitination process, have been demonstrated to play indispensable roles in regulating key biological processes in tumor cells, including DNA damage repair, cell cycle progression, apoptosis, cancer stem cell maintenance, and immune evasion. Additionally, E3 ligases are key regulators of resistance to multiple anticancer strategies, such as chemotherapy, radioth

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… This activates NRF2 signaling, upregulating glutathione peroxidase 4 (GPX4) and cystine transporter SLC7A11 expression, thereby suppressing ferroptosis and enhancing chemo-resistance ( Figure 5A ) ( 155 , 156 ). …

Mechanisms and Applications of Manganese-Based Nanomaterials in Tumor Diagnosis and Therapy.

Tumors are the second most common cause of mortality globally, ranking just below heart disease. With continuous advances in diagnostic technology and treatment approaches, the survival rates of some cancers have increased. Nevertheless, due to the complexity of the mechanisms underlying tumors, cancer remains a serious public health issue that threatens the health of the population globally. Manganese (Mn) is an essential trace element for the human body. Its regulatory role in tumor biology has received much attention in recent years. Developments in nanotechnology have led to the emergence

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… This process relies on GSH supplied by the cystine/glutamic acid transport system, particularly the Xc-system components recombinant solute carrier family 7, member 11 and recombinant solute carrier family 3, member 2 [ 44 ]. …

Food-derived compounds targeting ferroptosis for cancer therapy: from effects to mechanisms.

Ferroptosis is distinctive type programmed cell death. Tumor cells, with their higher iron levels, render them more susceptible to ferroptosis Inducing ferroptosis can activate immune cells, regulate immune evasion, and inhibit the biology activity of cancer cells. Therefore, ferroptosis-induced cancer cell death could become a promising approach for cancer treatment. Dietary compounds are an important source for drug discovery, and there has been an increasing amount of literature on food-derived ferroptosis inducers and their applications in cancer treatment. This review provides an overview

Withania somnifera: Progress towards a Pharmaceutical Agent for Immunomodulation and Cancer Therapeutics.

Chemotherapy is one of the prime treatment options for cancer. However, the key issues with traditional chemotherapy are recurrence of cancer, development of resistance to chemotherapeutic agents, affordability, late-stage detection, serious health consequences, and inaccessibility. Hence, there is an urgent need to find innovative and cost-effective therapies that can target multiple gene products with minimal adverse reactions. Natural phytochemicals originating from plants constitute a significant proportion of the possible therapeutic agents. In this article, we reviewed the advances and t

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… In addition, the leaves contain free amino acids including aspartic acid, glycine, tyrosine, alanine, proline, tryptophan, glutamic acid, and cystine. Fruits of Ashwagandha harbor a milk-coagulating enzyme, two esterases, free amino acids, fatty oil, essential oils, and alkaloids. …

Repurposing Pharmaceuticals Previously Approved by Regulatory Agencies to Medically Counter Injuries Arising Either Early or Late Following Radiation Exposure.

The increasing risks of radiological or nuclear attacks or associated accidents have served to renew interest in developing radiation medical countermeasures. The development of prospective countermeasures and the subsequent gain of Food and Drug Administration (FDA) approval are invariably time consuming and expensive processes, especially in terms of generating essential human data. Due to the limited resources for drug development and the need for expedited drug approval, drug developers have turned, in part, to the strategy of repurposing agents for which safety and clinical data are alrea

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… Cuprimine (Penicillamine - 3-mercapto- d -valine) is an FDA-approved agent for the indication of Wilson's disease (for removal of excess copper by binding), to reduce cystine excretion, and to treat rheumatoid arthritis ( MERCK and Co, 2004 ). …

Воспаление и воспаление болезней, маркеры и посредники: роль КПИ в некоторых воспламенительных заболеваниях

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… In chronic renal failure (CRF), GSH repression reduces the oral GSH precursor, F1 (contains cystine as a cysteine carrier), which attenuates oxidative stress and inflammation and restores tissue GSH and thus reduces the severity of interstitial nephropathy. …