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Neuroscience in peripheral cancers: tumors hijacking nerves and neuroimmune crosstalk.

Cancer neuroscience is an emerging field that investigates the intricate relationship between the nervous system and cancer, gaining increasing recognition for its importance. The central nervous system governs the development of the nervous system and directly affects brain tumors, and the peripheral nervous system (PNS) shapes the tumor microenvironment (TME) of peripheral tumors. Both systems are crucial in cancer initiation and progression, with recent studies revealing a more intricate role of the PNS within the TME. Tumors not only invade nerves but also persuade them through remodeling

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… Norepinephrine induces anoikis resistance in high‐grade serous ovarian cancer precursor cells. JCI Insight. 2024;9(5):e170961. 85. …

Overcoming Drug Resistance in Advanced Prostate Cancer by Drug Repurposing.

Prostate cancer (PCa) is the second most common cancer in men. Common treatments include active surveillance, surgery, or radiation. Androgen deprivation therapy and chemotherapy are usually reserved for advanced disease or biochemical recurrence, such as castration-resistant prostate cancer (CRPC), but they are not considered curative because PCa cells eventually develop drug resistance. The latter is achieved through various cellular mechanisms that ultimately circumvent the pharmaceutical's mode of action. The need for novel therapeutic approaches is necessary under these circumstances. An

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… lipins | Halted PCa proliferation Promoted autophagy vesicles and hence cancer cell death [ 138 ] | Digoxin | Anti-arrhythmic | | | Inhibition of Na + /K + ATPase pump which increases intracellular Ca 2+ levels | [ 138 , 139 ] | Ouabain | Anti-arrhythmic | PPC-1 | Male SCID | | Sensitize PPC-1 to anoikis …

Circulating Tumour Cells (CTCs) in NSCLC: From Prognosis to Therapy Design.

Designing optimal (neo)adjuvant therapy is a crucial aspect of the treatment of non-small-cell lung carcinoma (NSCLC). Standard methods of chemotherapy, radiotherapy, and immunotherapy represent effective strategies for treatment. However, in some cases with high metastatic activity and high levels of circulating tumour cells (CTCs), the efficacy of standard treatment methods is insufficient and results in treatment failure and reduced patient survival. CTCs are seen not only as an isolated phenomenon but also a key inherent part of the formation of metastasis and a key factor in cancer death.

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… For example, Sun et al. reported that activation of the PI3K/Akt/NF-κB/tyrosine kinase B (TrkB) pathway led to resistance of cancer cells to anoikis and thereby higher metastatic activity in a mouse model of hepatocellular carcinoma [ 295 ]. …

Oncogenic influences of neurotrophin receptors: Shedding light on Trk biology.

During critical stages of neurodevelopment, tropomyosin receptor kinase receptors, encoded by NTRK genes, exhibit temporally driven differential peaks of expression to properly guide the establishment of the peripheral and central nervous systems. In addition, these neuronal systems exhibit non-canonical regulation of surrounding tissues, impacting organogenesis, homeostasis, plasticity, and regeneration. The same processes that guide neurodevelopment, such as differentiation, plasticity, and neuronal survival, are also hijacked in cancer, making the NTRK family an ideal candidate to study. Th

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… invasion, increased lymph node metastases, advanced TNM, poorer overall survival 37 NTRK3 | TrkC Overactivation | triple-negative breast cancer 88 | NGFR binds to TrkC to activate its downstream signaling pathways to increase expression levels of NGFR and to promote growth and metastasis and resist anoikis … triple-negative breast cancer, which contains high NGFR levels. 88 Through this activation, downstream signaling pathways MEK/ERK1 and PI3K/AKT activate the transcriptional machinery to promote the overexpression of NGFR. 88 Both NGFR and TrkC independently and synergistically promoted sphere formation, anoikis …

The Molecular Aspect of Antitumor Effects of Protease Inhibitor Nafamostat Mesylate and Its Role in Potential Clinical Applications.

Nafamostat mesylate (NM), a synthetic serine protease inhibitor first placed on the market by Japan Tobacco in 1986, has been approved to treat inflammatory-related diseases, such as pancreatitis. Recently, an increasing number of studies have highlighted the promising effects of NM in inhibiting cancer progression. Alone or in combination treatments, studies have shown that NM attenuates various malignant tumors, including pancreatic, colorectal, gastric, gallbladder, and hepatocellular cancers. In this review, based on several activating pathways, including the canonical Nuclear factor-κB (N

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… Another study showed that the activity of intercellular adhesion molecule-1 (ICAM-1), VEGF, and MMP-9, the downstream transcription target genes of NF-κB ( 34 – 36 ), were stifled owing to NM-induced suppression of NF-κB activity, inhibiting pancreatic cancer cell adhesion, anoikis, and invasion ( 13 …

New Insights into the Pathogenesis of Systemic Mastocytosis.

Mastocytosis is a type of myeloid neoplasm characterized by the clonal, neoplastic proliferation of morphologically and immunophenotypically abnormal mast cells that infiltrate one or more organ systems. Systemic mastocytosis (SM) is a more aggressive variant of mastocytosis with extracutaneous involvement, which might be associated with multi-organ dysfunction or failure and shortened survival. Over 80% of patients with SM carry the KIT D816V mutation. However, the KIT D816V mutation serves as a weak oncogene and appears to be a late event in the pathogenesis of mastocytosis. The management o

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… Suppression of anoikis and induction of metastasis by the neurotrophic receptor TrkB Nature 2004 430 1034 1039 10.1038/nature02765 15329723 33. Drilon A. Laetsch T.W. Kummar S. DuBois S.G. Lassen U.N. Demetri G.D. Nathenson M. Doebele R.C. Farago A.F. Pappo A.S. …

Anti-tumor effect of inhibition of IL-6 signaling in mucoepidermoid carcinoma.

Mucoepidermoid carcinoma (MEC) is the most frequent malignant salivary gland cancer. Response to chemoradiotherapy is modest, and therefore radical surgery remains the standard-of-care. Emerging evidence suggests that Interleukin (IL)-6 signaling correlates with the survival of cancer stem cells and resistance to therapy. Here, we investigated whether inhibition of IL-6 receptor (IL-6R) signaling with tocilizumab (humanized anti-human IL-6R antibody) sensitizes MEC to chemotherapy using human mucoepidermoid carcinoma cell lines (UM-HMC) and correspondent xenograft models. In vitro, we observed

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… Cross talk initiated by endothelial cells enhances migration and inhibits anoikis of squamous cell carcinoma cells through STAT3/Akt/ERK signaling. Neoplasia. 2009;11:583–593. doi: 10.1593/neo.09266. 33. Zhang Z, Dong Z, Lauxen IS, Filho MSA, Nör JE. …

Emerging Mechanisms and Treatment Progress on Liver Metastasis of Colorectal Cancer.

Colorectal cancer is currently the third largest malignant tumor in the world, with high new cases and high mortality. Metastasis is one of the most common causes of death of colorectal cancer, of which liver metastasis is the most fatal. Since the beginning of the Human Genome Project in 2001, people have gradually recognized the 3 billion base pairs that make up the human genome, of which only about 1.5% of the nucleic acid sequences are used for protein coding, including proto-oncogenes and tumor suppressor genes. A large number of differences in the expression of proto-oncogenes and tumor

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… Genes in Liver Metastasis of Colorectal Cancer Genes Major Effects Receptors/Inhibitor Reference CXCL8 CXCL8 and its receptors have also been known to induce the epithelial-mesenchymal transition (EMT) of CRC cells, to help them to escape host immunosurveillance as well as to enhance resistance to anoikis … in Liver Metastasis of Colorectal Cancer Genes | Major Effects | Receptors/Inhibitor | Reference CXCL8 | CXCL8 and its receptors have also been known to induce the epithelial-mesenchymal transition (EMT) of CRC cells, to help them to escape host immunosurveillance as well as to enhance resistance to anoikis …

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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… Mechanisms that link the oncogenic epithelial-mesenchymal transition to suppression of anoikis . …

Immunotherapy for Colorectal Cancer: Mechanisms and Predictive Biomarkers.

Though early-stage colorectal cancer has a high 5 year survival rate of 65-92% depending on the specific stage, this probability drops to 13% after the cancer metastasizes. Frontline treatments for colorectal cancer such as chemotherapy and radiation often produce dose-limiting toxicities in patients and acquired resistance in cancer cells. Additional targeted treatments are needed to improve patient outcomes and quality of life. Immunotherapy involves treatment with peptides, cells, antibodies, viruses, or small molecules to engage or train the immune system to kill cancer cells. Preclinical

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… 22 , 23 ] CD3 | CD8+ T cells, CD4+ T cells | Used in bsTCEs to engage T cells | [ 24 ] GPA33 | Cancer cells | Function unclear; overexpressed in CRC | [ 25 , 26 ] GUCY2C | Cancer cells | Maintains intestinal homeostasis | [ 27 ] CEA | Cancer cells | May inhibit cell differentiation, apoptosis, and anoikis … CEA levels are expected to fall after surgical resection of the tumor [ 97 ] and overexpression may contribute to human cancer progression by inhibiting cell differentiation, apoptosis, and anoikis [ 28 ]. Preclinical evaluations have thus far demonstrated positive anti-tumor activity. …

Immune infiltration related PRDX4 facilitates the malignant features and drug resistance of breast cancer.

The incidence of breast cancer continues to increase annually, posing a significant challenge for countries worldwide in terms of its prevention and treatment. Therefore, identifying novel therapeutic targets for breast cancer is urgently needed. The peroxiredoxin (PRDX) family is regarded as a good diagnostic marker for various tumors. However, the expression and prognostic significance of PRDX family members in breast cancer remain unclear and require systematic investigation. By using bioinformatic tools such as UALCAN, TIMER2.0, Human Protein Atlas Project (HPA), Gene Set Cancer Analysis (

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… Peroxiredoxin 4 suppresses anoikis and augments growth and metastasis of hepatocellular carcinoma cells through the beta-catenin/ID2 pathway. Cell. Oncol. (Dordr . 42 , 769–781 (2019). 48. Jiang, M. et al. …

JAK inhibition in PD-1 immunotherapy and tumor microenvironment.

Targeting the programmed cell death 1 (PD-1)/PD-L1 axis has revolutionized cancer therapy; however, the durability of clinical responses is frequently compromised by chronic inflammation and an immunosuppressive tumor microenvironment (TME). The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway serves as a central intracellular node integrating cytokine signals that drive these resistance mechanisms. While physiological JAK/STAT signaling is essential for antitumor immunity, its persistent aberrant activation promotes malignant progression, upregulates

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… A mechanism for epithelial-mesenchymal transition and anoikis resistance in breast cancer triggered by zinc channel ZIP6 and STAT3 (signal transducer and activator of transcription 3) . Biochem J . ( 2013 ) 455 : 229–37 . doi: 10.1042/BJ20130483 , PMID: 23919497 PMC3789231 63 Jin W . …

New Generation of Meso and Antiprogestins (SPRMs) into the Osteoporosis Approach.

Receptor activator of nuclear factor κB (RANK) and its ligand (RANKL) play key roles in bone metabolism and the immune system. The RANK/RANKL complex has also been shown to be critical in the formation of mammary epithelia cells. The female hormones estradiol and progesterone closely control the action of RANKL with RANK. Blood concentration of these sex hormones in the postmenopausal period leads to an increase in RANK/RANKL signaling and are a major cause of women's osteoporosis, characterized by altered bone mineralization. Knowledge of the biochemical relationships between hormones and RAN

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… RANK-Fc inhibits malignancy via inhibiting ERK activation and evoking caspase-3-mediated anoikis in human osteosarcoma cells. Clin. Exp. Metastasis. 2010;27:207–215. doi: 10.1007/s10585-010-9319-y. 34. …

Prospects and Advances in Adoptive Natural Killer Cell Therapy for Unmet Therapeutic Needs in Pediatric Bone Sarcomas.

Malignant bone tumors are aggressive tumors, with a high tendency to metastasize, that are observed most frequently in adolescents during rapid growth spurts. Pediatric patients with malignant bone sarcomas, Ewing sarcoma and osteosarcoma, who present with progressive disease have dire survival rates despite aggressive therapy. These therapies can have long-term effects on bone growth, such as decreased bone mineral density and reduced longitudinal growth. New therapeutic approaches are therefore urgently needed for targeting pediatric malignant bone tumors. Harnessing the power of the immune

The versatile emodin: A natural easily acquired anthraquinone possesses promising anticancer properties against a variety of cancers.

Cancers are generally recognized as the leading cause of death and a predominant barrier to prolonging life expectancy in both developed and developing countries. Emodin is a typical anthraquinone derivative from various plants that exhibits a wide spectrum of biological activities, such as anticancer, antibacterial, hepatoprotective and anti-inflammatory activities. Much previous preclinical evidence has demonstrated that emodin exhibits reliable effects on several cancer types, including lung cancer, liver cancer, colon cancer, breast cancer, pancreatic cancer, leukemia, cervical cancer, and

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… Cai et al. found that emodin, as an ROS producer, can combine with arsenic trioxide (ATO) to cause oxidative stress in SGC-7901 cells, promote RhoA inactivation, lead to actin silk breakage, and lead to structural destruction of the site adhesion complex, ultimately leading to anoikis, which can be partially …

The Confluence of Nanotechnology and Heat Shock Protein 70 in Pioneering Glioblastoma Multiforme Therapy: Forging Pathways Towards Precision Targeting and Transformation.

Heat-shock protein 70 (HSP70) and nanotechnology have emerged as promising avenues in glioblastoma multiforme (GBM) therapy, addressing the critical challenges posed by its aggressive nature and therapeutic resistance. HSP70's dual role in cellular stress response and tumour survival emphasises its potential as both a biomarker and therapeutic target. This review explores the innovative integration of HSP70 with nanotechnology, emphasising advancements in imaging, drug delivery and combination therapies. Nanoparticles, including SPIONs, liposomes, gold nanoparticles and metal-organic framework

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… These cells displayed characteristic EMT changes, including altered morphology, disrupted cell junctions, increased migration and enhanced sensitivity to anoikis. … This absence of HSP70 made cells more prone to anoikis and conferred mesenchymal traits and improved migratory capabilities. Previous hints about HSP70's involvement in EMT pathways were supported by this study, indicating that HSP70's presence delayed EMT by supporting cell adhesion. …

Bone Pain in Cancer Patients: Mechanisms and Current Treatment.

The skeletal system is the third most common site for cancer metastases, surpassed only by the lungs and liver. Many tumors, especially those of the breast, prostate, lungs, and kidneys, have a strong predilection to metastasize to bone, which causes pain, hypercalcemia, pathological skeletal fractures, compression of the spinal cord or other nervous structures, decreased mobility, and increased mortality. Metastatic cancer-induced bone pain (CIBP) is a type of chronic pain with unique and complex pathophysiology characterized by nociceptive and neuropathic components. Its treatment should be

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… Suppression of anoikis and induction of metastasis by the neurotrophic receptor TrkB. Nature. 2004;430:1034–1039. doi: 10.1038/nature02765. 27. Weiskopf K., Ring A.M., Ho C.C., Volkmer J.P., Levin A.M., Volkmer A.K., Ozkan E., Fernhoff N.B., van de Rijn M., Weissman I.L., et al. …

The Osteoclast in Bone Metastasis: Player and Target.

Bone metastases are frequently the final fate of breast and prostate cancer patients. According to the definition of metastasis as an incurable disease, to date there are no effective treatments for tumor-associated bone metastases and this represents a real challenge for the researchers in the field. The bone is a heterogeneous environment that represents a fertile soil for tumor cells, supporting their growth. Among the different cell types present in the bone, in this review we will focus our attention on the osteoclasts, which are crucial players in the so called “vicious cycle”, a phenome

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… Osteolytic bone metastasis is hampered by impinging on the interplay among autophagy, anoikis and ossification. Cell Death Dis. 2014;5:e1005. doi: 10.1038/cddis.2013.465. 111. …

Revitalizing Cancer Treatment: Exploring the Role of Drug Repurposing.

Cancer persists as a global challenge necessitating continual innovation in treatment strategies. Despite significant advancements in comprehending the disease, cancer remains a leading cause of mortality worldwide, exerting substantial economic burdens on healthcare systems and societies. The emergence of drug resistance further complicates therapeutic efficacy, underscoring the urgent need for alternative approaches. Drug repurposing, characterized by the utilization of existing drugs for novel clinical applications, emerges as a promising avenue for addressing these challenges. Repurposed d

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… Disulfiram induces anoikis and suppresses lung colonization in triple-negative breast cancer via calpain activation. Cancer Lett. 2017;386:151–160. doi: 10.1016/j.canlet.2016.11.022. 48. El Fawal G., Abu-Serie M.M., El-Gendi H., El-Fakharany E.M. …

Rethinking the Combination of Proton Exchanger Inhibitors in Cancer Therapy.

Microenvironmental acidity is becoming a key target for the new age of cancer treatment. In fact, while cancer is characterized by genetic heterogeneity, extracellular acidity is a common phenotype of almost all cancers. To survive and proliferate under acidic conditions, tumor cells up-regulate proton exchangers and transporters (mainly V-ATPase, Na⁺/H⁺ exchanger (NHE), monocarboxylate transporters (MCTs), and carbonic anhydrases (CAs)), that actively extrude excess protons, avoiding intracellular accumulation of toxic molecules, thus becoming a sort of survival option with many similarities

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… V-ATPase inhibition regulates anoikis resistance and metastasis of cancer cells Mol. Cancer Ther. 2014 13 926 937 10.1158/1535-7163.MCT-13-0484 24482380 59. Sennoune S.R. Bakunts K. Martinez G.M. Chua-Tuan J.L. Kebir Y. Attaya M.N. Martínez-Zaguilán R. …