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Opportunities and Challenges of Small Molecule Induced Targeted Protein Degradation.

Proteolysis targeting chimeras (PROTAC) represents a new type of small molecule induced protein degradation technology that has emerged in recent years. PROTAC uses bifunctional small molecules to induce ubiquitination of target proteins and utilizes intracellular proteasomes for chemical knockdown. It complements the gene editing and RNA interference for protein knockdown. Compared with small molecule inhibitors, PROTAC has shown great advantages in overcoming tumor resistance, affecting the non-enzymatic function of target proteins, degrading undruggable targets, and providing new rapid and

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… In order to prove that the degraders had no degrading activity on wild-type BRAF protein, they used compound 43 and compound 44 to perform protein degradation experiments on A549 cells (BRAF-WT), and they found that these two degraders had no degradation activity on the BRAF-WT protein at different concentrations …

Curcumin and Its Derivatives as Anticancer Agents in Head and Neck Cancer: Molecular Mechanisms and Preclinical Evidence

Head and neck cancer (HNC), particularly oral squamous cell carcinoma (OSCC), remains a major clinical challenge due to its aggressive behavior, high recurrence rates, and frequent resistance to conventional therapies. Natural compounds, especially curcumin and its derivatives, have gained increasing attention as potential anticancer agents due to their ability to target multiple molecular pathways involved in tumor progression. This review critically evaluates the current preclinical and translational evidence supporting curcumin and its derivatives as monotherapeutic agents in HNC, with part

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

Roles of Microvesicles in Tumor Progression and Clinical Applications.

Microvesicles are extracellular vesicles with diameter ranging from 100 to 1000 nm that are secreted by tumor cells or other cells in the tumor microenvironment. A growing number of studies demonstrate that tumor-derived microvesicles are involved in tumor initiation and progression, as well as drug resistance. In addition, tumor-derived microvesicles carry a variety of immunogenic molecules and inhibit tumor response to immunotherapy; therefore, they can be exploited for use in tumor vaccines. Moreover, because of their high stability, tumor-derived microvesicles extracted from body fluids ca

Lithium: A Promising Anticancer Agent.

Lithium is a therapeutic cation used to treat bipolar disorders but also has some important features as an anti-cancer agent. In this review, we provide a general overview of lithium, from its transport into cells, to its innovative administration forms, and based on genomic, transcriptomic, and proteomic data. Lithium formulations such as lithium acetoacetate (LiAcAc), lithium chloride (LiCl), lithium citrate (Li3C6H5O7), and lithium carbonate (Li2CO3) induce apoptosis, autophagy, and inhibition of tumor growth and also participate in the regulation of tumor proliferation, tumor invasion, and

The role of necroptosis in disease and treatment.

Necroptosis, a distinctive type of programmed cell death different from apoptosis or necrosis, triggered by a series of death receptors such as tumor necrosis factor receptor 1 (TNFR1), TNFR2, and Fas. In case that apoptosis process is blocked, necroptosis pathway is initiated with the activation of three key downstream mediators which are receptor-interacting serine/threonine protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like protein (MLKL). The whole process eventually leads to destruction of the cell membrane integrity, swelling of organelles, and severe inflammation. Ove

Cancer vaccines: an update on recent achievements and prospects for cancer therapy.

Decades of basic and translational research have led to a momentum shift in dissecting the relationship between immune cells and cancer. This culminated in the emergence of breakthrough immunotherapies that paved the way for oncologists to manage certain hard-to-treat cancers. The application of high-throughput techniques of genomics, transcriptomics, and proteomics was conclusive in making and expediting the manufacturing process of cancer vaccines. Using the latest research technologies has also enabled scientists to interpret complex and multiomics data of the tumour mutanome, thus identify

Emerging and underexplored ginsenosides in cancer therapy (2020-2025): Beyond cytotoxic mechanisms.

Ginsenosides from Panax plants have long been studied as potential anticancer agents. In earlier years, most research focused on a few well-known ginsenosides that showed strong direct cytotoxicity, such as Rg3 and Rh2. As a result, many other ginsenosides were considered less active and received limited attention. However, studies published between 2020 and 2025 indicate that several previously underexplored ginsenosides also exhibit meaningful anticancer activity. These compounds often do not function as strongly cytotoxic agents. Instead, they act through broader and more indirect mechanism

Epigenetic Mechanisms in DNA Double Strand Break Repair: A Clinical Review.

Upon the induction of DNA damage, the chromatin structure unwinds to allow access to enzymes to catalyse the repair. The regulation of the winding and unwinding of chromatin occurs via epigenetic modifications, which can alter gene expression without changing the DNA sequence. Epigenetic mechanisms such as histone acetylation and DNA methylation are known to be reversible and have been indicated to play different roles in the repair of DNA. More importantly, the inhibition of such mechanisms has been reported to play a role in the repair of double strand breaks, the most detrimental type of DN

Nanoparticle-based strategy in CAR-T cell immunotherapy: challenges, implications, and perspectives.

Chimeric antigen receptor (CAR)-T cell therapy has achieved remarkable progress in treating hematologic malignancies, yet its broader application faces challenges such as manufacturing complexity, solid tumor microenvironment barriers, and immune toxicity. Nanoparticles (NPs), leveraging their precise delivery, immunomodulation, and multifunctional integration capabilities, offer innovative strategies to optimize CAR-T cell therapy. This review provides a comprehensive elucidation of the fundamental framework of CAR-T cell therapy and the challenges in oncological applications. Subsequently, w

The Role of IL-33/ST2 Pathway in Tumorigenesis.

Cancer is initiated by mutations in critical regulatory genes; however, its progression to malignancy is aided by non-neoplastic cells and molecules that create a permissive environment known as the tumor stroma or microenvironment (TME). Interleukin 33 (IL-33) is a dual function cytokine that also acts as a nuclear factor. IL-33 typically resides in the nucleus of the cells where it is expressed. However, upon tissue damage, necrosis, or injury, it is quickly released into extracellular space where it binds to its cognate receptor suppression of tumorigenicity 2 (ST2)L found on the membrane o

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… Overexpression of IL-33 by transfection into NSCLC cells isolated from patients [ 91 ] and treatment of human lung A549 cells with IL-33 [ 92 ] enhanced tumor outgrowth, migration, invasion, and metastasis in an ST2-dependent manner. …

PIM1 kinase and its diverse substrate in solid tumors.

The PIM kinase family, consisting of PIM1, PIM2, and PIM3, is a group of serine/threonine protein kinases crucial for cellular growth, immunoregulation, and oncogenesis. PIM1 kinase is often overexpressed in solid and hematopoietic malignancies, promoting cell survival, proliferation, migration, and senescence by activating key genes. In vitro and in vivo studies have established the oncogenic potential of PIM1 kinases. These kinases have been implicated in tumor progression, metastasis, and resistance to chemotherapy, underscoring their potential as a therapeutic target for cancer therapy. Th

Nanobodies Enhancing Cancer Visualization, Diagnosis and Therapeutics.

Worldwide, cancer is a serious health concern due to the increasing rates of incidence and mortality. Conventional cancer imaging, diagnosis and treatment practices continue to substantially contribute to the fight against cancer. However, these practices do have some risks, adverse effects and limitations, which can affect patient outcomes. Although antibodies have been developed, successfully used and proven beneficial in various oncology practices, the use of antibodies also comes with certain challenges and limitations (large in size, poor tumor penetration, high immunogenicity and a long

Repurposing Drugs in Oncology (ReDO)-diclofenac as an anti-cancer agent.

Diclofenac (DCF) is a well-known and widely used non-steroidal anti-inflammatory drug (NSAID), with a range of actions which are of interest in an oncological context. While there has long been an interest in the use of NSAIDs in chemoprevention, there is now emerging evidence that such drugs may have activity in a treatment setting. DCF, which is a potent inhibitor of COX-2 and prostaglandin E2 synthesis, displays a range of effects on the immune system, the angiogenic cascade, chemo- and radio-sensitivity and tumour metabolism. Both pre-clinical and clinical evidence of these effects, in mul

Chronic Psychological Stress in Oncogenesis: Multisystem Crosstalk and Multimodal Interventions.

Malignant tumors constitute a major global public health burden. Chronic psychological stress (CPS) manifests as sustained dysregulation arising from prolonged adaptive responses to chronic endogenous and exogenous stimuli. Clinical evidence indicates that CPS markedly influences cancer progression, with most oncology patients developing detectable stress-related psychological disorders during disease management. This review synthesizes recent advances in understanding CPS-mediated oncogenic mechanisms and evaluates current intervention approaches. Mechanistically, CPS compromises immune surve

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… Activated O2(•−) and H 2 O 2 mediated cell survival in SU11274-treated non-small-cell lung cancer A549 cells via c-met-PI3K-Akt and c-met-Grb2/SOS-Ras-p38 pathways. J Pharmacol Sci. 2012;119(2):150–159. 83. Lin YJ, Yang CC, Lee IT, Wu WB, Lin CC, Hsiao LD, Yang CM. …

Piperine: From Green Extraction to Clinical Translation-A Review.

BACKGROUND: Piperine has diverse pharmacological and bioenhancing activities, but poor aqueous solubility, variable exposure, interaction liability, and discontinuity across production, formulation, and clinical evaluation limit translation. This review integrates these frequently separated stages. METHODS: A structured narrative PubMed search covered English-language studies published from 1 January 2021 to 27 April 2026, supplemented by ClinicalTrials.gov records checked through 13 June 2026, backward citation searching, and selected earlier seminal studies. Evidence was synthesized by expe

NKG2D CAR-T cells for solid tumor immunotherapy: advances, challenges, and future directions.

Chimeric antigen receptor (CAR) T-cell therapy has achieved significant success in hematologic malignancies, but its efficacy in solid tumors remains limited, primarily due to the immunosuppressive tumor microenvironment (TME) that hinders CAR-T cell trafficking and function. NKG2D CAR-T cells, which target stress-induced NKG2D ligands (NKG2DLs) broadly expressed on tumor cells, have shown promising potential in overcoming the immunosuppressive barriers of the solid TME. This review highlights recent advances in NKG2D CAR-T cell strategies for solid tumors, including innovations in CAR archite

Свойства антиракера ВИЧ-ингибатора Нелфинавира.

Традиционные методы лечения рака могут потерять свою эффективность после появления новых мутации или развития химиотерапии. Несвоевременная диагностика, высокая стоимость лечения и потребность в высокоэффективной инфраструктуре для лечения раковых заболеваний затрудняют доступ к надлежащему лечению в условиях с низким уровнем доходов и ограниченными ресурсами. Переориентация утвержденных лекарственных средств на лечение рака может привести к снижению стоимости и сокращению сроков разработки новых лекарственных средств и к ускорению появления новых и эффективных вариантов лечения для нуждающихс

MSC-derived extracellular vesicles: Precision miRNA delivery for overcoming cancer therapy resistance.

Cancer remains a prominent worldwide health concern, presenting existing therapies with frequent difficulties, including major toxicity, limited effectiveness, and treatment resistance emergence. These issues highlight the necessity for novel and enhanced remedies. Exosomes, tiny extracellular vesicles that facilitate intercellular communication, have attracted interest for their potential medicinal applications. Carrying a variety of molecules, including microRNAs, small interfering RNAs, long non-coding RNAs, proteins, lipids, and DNA, these vesicles are positioned as promising cancer treatm

Exosome-based miRNA delivery: Transforming cancer treatment with mesenchymal stem cells.

Recently, increasing interest has been in utilizing mesenchymal stem cell-derived extracellular vesicles (MSC-EVs), especially exosomes, as nanocarriers for miRNA delivery in cancer treatment. Due to such characteristics, nanocarriers are specific: biocompatible, low immunogenicity, and capable of spontaneous tumor accumulation. MSC-EVs were loaded with therapeutic miRNAs and minimized their susceptibility to degradation by protecting the miRNA from accessibility to degrading enzymes and providing targeted delivery of the miRNAs to the tumor cells to modulate oncogenic pathways. In vitro and i