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Hematopoietic cell kinase (Hck), a non-receptor tyrosine kinase belonging to the Src kinase family, is intricately linked to the pathogenesis of numerous human diseases, with a particularly pronounced association with cancer. Hck not only directly impacts the proliferation, migration, and apoptosis of cancer cells but also interacts with JAK/STAT, MEK/ERK, PI3K/AKT, CXCL12/CXCR4, and other pathways. Hck also influences the tumor microenvironment to facilitate the onset and progression of cancer. This paper delves into the functional role and regulatory mechanisms of Hck in various solid tumors. Additionally, it explores the implications of Hck in hematological malignancies. The review culminates with a summary of the current research status of Hck inhibitors, the majority of which are in the pre-clinical phase of investigation. Notably, these inhibitors are predominantly utilized in the therapeutic management of leukemia, with their combinatorial potential indicating promising avenues for future research. In conclusion, this review underscores the significance of the mechanism of Hck in solid tumors. This insight is crucial for comprehending the current research trends regarding Hck: targeted therapy against Hck shows great promise in both diagnosis and treatment of malignant tumors. Further investigation into the role of Hck in cancer, coupled with the development of specific inhibitors, has the potential to revolutionize approaches to cancer treatment. [Display omitted] • Hck is closely associated with a variety of solid tumors and hematological tumors. • Hck directly modulates cancer cell behavior, influencing proliferation, migration, and apoptosis. • Hck's involvement in key signaling pathways and the tumor microenvironment is crucial for cancer progression. • Hck inhibitors are in preclinical development and show promise in combination with other drugs. [ABSTRACT FROM AUTHOR]

This paper explores the therapeutic perspectives of polyphenols and chitosan as potential anticancer agents in the mouthwash formulations. Taking into account the high incidence of squamous cell carcinoma (SCC) among oral cancers, this discussion will concentrate on the potential advantages of these compounds in oral care, focusing on their impact on improving oral health and cancer prevention. According to the data, it appears that the mixture of BACs extract and chitosan may increase the efficiency of the apoptosis of cancer cells while reducing the undesired side effects. The cytotoxicity assays demonstrate a significant reduction in squamous carcinoma cell viability after incubation with BACs extract, with a marked decrease observed over 24–72 hours up to 76%. The anti-cancer properties of the BAC extract are related to luteolin, which is a predominant compound. The addition of 0.025% chitosan reduced the metabolic activity of cancer cells by 37.5%, suggesting a synergistic interaction between the compounds. This research highlights the potential of BACs and chitosan in modulating important molecular targets associated with cancer cell. [Display omitted] [ABSTRACT FROM AUTHOR]

Lung cancer represents a significant global health concern and stands as the leading cause of cancer-related mortality worldwide. The identification of specific genomic alterations such as EGFR and KRAS in lung cancer has paved the way for the development of targeted therapies. While targeted therapies for lung cancer exhibiting EGFR , MET and ALK mutations have been well-established, the options for RET mutations remain limited. Importantly, RET mutations have been found to be mutually exclusive from other genomic mutations and to be related with high incidences of brain metastasis. Given these facts, it is imperative to explore the development of RET-targeting therapies and to elucidate the mechanisms underlying metastasis in RET-expressing lung cancer cells. In this study, we investigated PLM-101, a novel dual-target inhibitor of RET/YES1, which exhibits notable anti-cancer activities against CCDC6-RET-positive cancer cells and anti-metastatic effects against YES1-positive cancer cells. Our findings shed light on the significance of the YES1-Cortactin-actin remodeling pathway in the metastasis of lung cancer cells, establishing YES1 as a promising target for suppression of metastasis. This paper unveils a novel inhibitor that effectively targets both RET and YES1, thereby demonstrating its potential to impede the growth and metastasis of RET rearrangement lung cancer. [Display omitted] • The CCDC6-RET gene contributes to the growth and survival of lung cancer cells by activating the PI3K and RAS pathways. • YES1 regulates Cortactin activity to facilitate actin polymerization-dependent cancer cell metastasis. • PLM-101, a novel RET/YES1 dual-target inhibitor, effectively suppresses primary and metastatic secondary lung cancer. [ABSTRACT FROM AUTHOR]

This paper explores the therapeutic perspectives of polyphenols and chitosan as potential anticancer agents in the mouthwash formulations. Taking into account the high incidence of squamous cell carcinoma (SCC) among oral cancers, this discussion will concentrate on the potential advantages of these compounds in oral care, focusing on their impact on improving oral health and cancer prevention. According to the data, it appears that the mixture of BACs extract and chitosan may increase the efficiency of the apoptosis of cancer cells while reducing the undesired side effects. The cytotoxicity assays demonstrate a significant reduction in squamous carcinoma cell viability after incubation with BACs extract, with a marked decrease observed over 24–72 hours up to 76%. The anti-cancer properties of the BAC extract are related to luteolin, which is a predominant compound. The addition of 0.025% chitosan reduced the metabolic activity of cancer cells by 37.5%, suggesting a synergistic interaction between the compounds. This research highlights the potential of BACs and chitosan in modulating important molecular targets associated with cancer cell.

The high expression of BLM (Bloom syndrome) DNA helicase in tumors involves its strong association with cell expansion. Bisbenzylisoquinoline alkaloids own an antitumor property and have developed as candidates for anticancer drugs. This paper aimed to study the antitumor effect of fangchinoline derivative HY-2 by targeting BLM642–1290 DNA helicase, and then explore its inhibitory mechanism on proliferation of MDA-MB-435 breast cancer cells. We confirmed that the mRNA and protein levels of BLM DNA helicase in breast cancer were higher than those in normal tissues. HY-2 could inhibit the DNA binding, ATPase and DNA unwinding of BLM642–1290 DNA helicase with enzymatic assay. HY-2 could also inhibit the DNA unwinding of DNA helicase in cells. In addition, HY-2 showed an inhibiting the MDA-MB-435, MDA-MB-231, MDA-MB-436 breast cancer cells expansion. The mRNA and protein levels of BLM DNA helicase in MDA-MB-435 cells increased after HY-2 treatment, which might contribute to HY-2 inhibiting the DNA binding, ATPase and DNA unwinding of BLM DNA helicase. The mechanism of HY-2 inhibition on BLM DNA helicase was further confirmed with the effect of HY-2 on the ultraviolet spectrogram of BLM642–1290 DNA helicase and Molecular dynamics simulation of the interacting between HY-2 and BLM640–1291 DNA helicase. Our study provided some valuable clues for the exploration of HY-2 in the living body and developing it as an anticancer drug. [Display omitted] • We identified a new small-molecule BLM DNA helicase inhibitor, fangchinoline derivative HY-2. • HY-2 inhibits breast cancer cells expansion, which associated with it suppressing BLM DNA helicase. • HY-2 is expected to be a therapeutic candidate for breast cancer. [ABSTRACT FROM AUTHOR]

Oncogenesis and the development of tumors affect metabolism throughout the body. Metabolic reprogramming (also known as metabolic remodeling) is a feature of malignant tumors that is driven by oncogenic changes in the cancer cells themselves as well as by cytokines in the tumor microenvironment. These include endothelial cells, matrix fibroblasts, immune cells, and malignant tumor cells. The heterogeneity of mutant clones is affected by the actions of other cells in the tumor and by metabolites and cytokines in the microenvironment. Metabolism can also influence immune cell phenotype and function. Metabolic reprogramming of cancer cells is the result of a convergence of both internal and external signals. The basal metabolic state is maintained by internal signaling, while external signaling fine-tunes the metabolic process based on metabolite availability and cellular needs. This paper reviews the metabolic characteristics of gastric cancer, focusing on the intrinsic and extrinsic mechanisms that drive cancer metabolism in the tumor microenvironment, and interactions between tumor cell metabolic changes and microenvironment metabolic changes. This information will be helpful for the individualized metabolic treatment of gastric cancers. [Display omitted] • The article describes metabolic reprogramming of gastric cancer cells and the impact of metabolic reprogramming on the microenvironment. • The effects of metabolic reprogramming of the tumor microenvironment on the proliferation, migration, and drug resistance of tumor cells. • The article proceeds to the interactions between gastric malignancies and the microenvironment, including immune cells, stromal cells, microbiota, etc. • The article introduces immunotherapy for gastric cancer and the relationship with metabolic changes in the microenvironment. • This article provides a review of the drugs targeting the metabolic pathway of gastric cancer, discusses the current dilemma. [ABSTRACT FROM AUTHOR]

Compounds containing Michael acceptor units display a wide variety of biological effects, and have attracted much attention in medicinal chemistry. In this paper, we designed and synthesized a panel of para -quinone methides (p -QMs) derivatives, classified as electron-deficient alkenes, and evaluated their cytotoxicity against cancer cells. These results revealed that drawing substituents into the ortho -position of the phenyl ring could obviously strengthen the cytotoxicity of p -QMs derivatives compared with that of meta - and para -substituents. Further biological studies demonstrated that the cytotoxicity of p -QMs derivatives originated from their ROS-generation abilities, which could further disrupt the redox balance, lipid peroxidation, the loss of MMP, cell cycle arrest at G0/G1 phase and apoptosis. 1h also exhibited potent antitumor activity through inhibiting TrxR and activating Bax and caspase 3 expression in vitro and in vivo , and 1h had certain safety in vivo. Moreover, the electrophilicity of the Michael acceptor, which could covalently modify with the TrxR, play a potent role in the ROS generation. From the perspective of chemistry, we affirmed that p -QMs derivatives could rapidly covalent binding with cysteamine, and the addition product was characterized by 1H NMR. Together, these new p -QMs derivatives may possess potential as leads for development of effective antitumor agents. [Display omitted] • p -QMs derivatives exhibited moderate to good cytotoxicity on cancer cells. • p -QMs derivatives showed strong electrophilicity and rapidly reacted with cysteamine. • p -QMs derivative 1h displayed potent antitumor activity by inhibiting TrxR in vitro and in vivo. • 1h had certain safety in vivo. [ABSTRACT FROM AUTHOR]

The surface of silver nanoparticles (AgNPs) is characterized by high reactivity resulting in prooxidative and cytotoxic properties. These effects are observed both in normal and in cancer cells, which overexpress the Epidermal Growth Factor Receptor (EGFR). In our previous paper, we have demonstrated that, with the use of liposomes labeled with the Epidermal Growth Factor (EGF), it is possible to direct the toxic effect of AgNPs in EGFR-overexpressing cells. Unfortunately, the mechanism of uptake and toxicity induction by such liposomes is still unknown. Therefore, the aim of this study was to determine the impact of EGF-LipoAgNPs on certain genes related to endocytosis and toxicity induction by such liposomes in human lung (A549) and tongue (SCC-15) cancer cells. The siRNA knock-out gene method was used in this study to determine the engagement of EGFR in this process. The confocal microscopy study revealed that the number of liposomes in the cytoplasm of the A549EGFR- and SCC-15EGFR- cells was lowered by 51.99 × 103 RFU and 138.50 × 103 RFU, respectively, proving the crucial role of EGFR in the liposome uptake. Moreover, the expression of the SHH and ATM genes was significantly increased, whereas the expression of the NRF2 gene was decreased after the treatment with EGF-LipoAgNPs and native AgNPs. Furthermore, the expression of the CLTC, AP2M1, CAV1 , and SH3GLB1 genes indicated that the tested liposomes are uptaken via the clathrin-dependent pathway with engagement of the AP-2 complex and endophilin in this process. Summarizing, the created targeted delivery system of AgNPs causes an increase in the prooxidative and toxic effect of such NPs and has an impact on endocytosis regulatory genes, especially those related to the clathrin-mediated endocytosis. [Display omitted] • The amount of EGF-LipoAgNPs in EGFR+ cells was significantly increased, compared to the EGFR- cells. • EGF-LipoAgNPs increased the expression of the SHH and ATM genes more effectively than native AgNPs. • The EGF-LipoAgNP liposomes downregulated NFR2 gene expression as in AgNPs-treated cells. • EGF-LipoAgNPs and EGF-LipoE were uptaken via the clathrin-dependent pathway. • The tested liposomes had an impact on the AP2M1 and SH3GLB1 endocytosis regulatory genes. [ABSTRACT FROM AUTHOR]