Semaphorins as emerging clinical biomarkers and therapeutic targets in cancer.
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ABSTRACT:
SUBMITTER: Mastrantonio R
PROVIDER: S-EPMC7847692 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Semaphorins are a large class of secreted or membrane-bound molecules. It has been reported that semaphorins play important roles in regulating several hallmarks of cancer, including angiogenesis, metastasis, and immune evasion. Semaphorins and their receptors are widely expressed on tumor cells and immune cells. However, the biological role of semaphorins in tumor immune microenvironment is intricate. The dysregulation of semaphorins influences the recruitment and infiltration of immune cells, leading to abnormal anti-tumor effect. Although the underlying mechanisms of semaphorins on regulating tumor-infiltrating immune cell activation and functions are not fully understood, semaphorins can notably be promising immunotherapy targets for cancer.
| S-EPMC8830438 | biostudies-literature
Project description:BackgroundInitially characterized as axon guidance factors, semaphorins also have been implicated to have critical roles in multiple physiological and developmental functions, including the regulation of immune responses, angiogenesis, organ formation, and the etiology of multiple forms of cancer. Moreover, their contribution in immunity and the regulation of tumour microenvironment is becoming increasingly recognized. Here, we provide a comprehensive analysis of class-3 semaphorins, the only secreted family of genes among veterbrate semaphorins, in terms of their expression profiles and their association with patient survival. We also relate their role with immune subtypes, tumour microenvironment, and drug sensitivity using a pan-cancer study.ResultsExpression profiles of class-3 semaphorins (SEMA3s) and their association with patient survival and tumour microenvironment were studied in 31 cancer types using the TCGA pan-cancer data. The expression of SEMA3 family varies in different cancer types with striking inter- and intra- cancer heterogeneity. In general, our results show that SEMA3A, SEMA3C, and SEMA3F are primarily upregulated in cancer cells, while the rest of SEMA3s are mainly down-regulated in the tested tumours. The expression of SEMA3 family members was frequently associated with patient overall survival. However, the direction of the association varied with regards to the particular SEMA3 isoform queried and the specific cancer type tested. More specifically, SEMA3A and SEMA3E primarily associate with a poor prognosis of survival, while SEMA3G typically associates with survival advantage. The rest of SEMA3s show either survival advantage or disadvantage dependent on cancer type. In addition, all SEMA3 genes show significant association with immune infiltrate subtypes, and they also correlate with level of stromal cell infiltration and tumour cell stemness with various degrees. Finally, our study revealed that SEMA3 genes, especially SEMA3C and SEMA3F may contribute to drug induced cancer cell resistance.ConclusionsOur systematic analysis of class-3 semaphorin gene expression and their association with immune infiltrates, tumour microenvironment and cancer patient outcomes highlights the need to study each SEMA3 member as a separate entity within each specific cancer type. Also our study validated the identification of class-3 semaphorin signals as promising therapeutic targets in cancer although further laboratory validation still needed.
| S-EPMC7118829 | biostudies-literature
Project description:The axonal guidance molecules, semaphorins, have been described to function both physiologically and pathologically outside of the nervous system. In this review, we focus on the vertebrate semaphorins found in classes 3 through 7 and their roles in vascular development and autoimmune diseases. Recent studies indicate that while some of these vertebrate semaphorins promote angiogenesis, others have an angiostatic function. Since some semaphorins are also expressed by different immune cells and are known to modulate immune responses, they have been implicated in autoimmune disorders such as multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus and systemic sclerosis. We conclude this review by addressing strategies targeting semaphorins as potential therapeutic agents for angiogenesis and autoimmune diseases.
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Project description:Diabetic neuropathy (DN) is the most prevalent chronic complication of diabetes mellitus. The exact pathophysiological mechanisms of DN are unclear; however, communication network dysfunction among axons, Schwann cells, and the microvascular endothelium likely play an important role in the development of DN. Mounting evidence suggests that microRNAs (miRNAs) act as messengers that facilitate intercellular communication and may contribute to the pathogenesis of DN. Deregulation of miRNAs is among the initial molecular alterations observed in diabetics. As such, miRNAs hold promise as biomarkers and therapeutic targets. In preclinical studies, miRNA-based treatment of DN has shown evidence of therapeutic potential. But this therapy has been hampered by miRNA instability, targeting specificity, and potential toxicities. Recent findings reveal that when packaged within extracellular vesicles, miRNAs are resistant to degradation, and their delivery efficiency and therapeutic potential is markedly enhanced. Here, we review the latest research progress on the roles of miRNAs as biomarkers and as potential clinical therapeutic targets in DN. We also discuss the promise of exosomal miRNAs as therapeutics and provide recommendations for future research on miRNA-based medicine.
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Project description:Cancer care has witnessed remarkable progress in recent decades, with a wide array of targeted therapies and immune-based interventions being added to the traditional treatment options such as surgery, chemotherapy, and radiotherapy. However, despite these advancements, the challenge of achieving high tumor specificity while minimizing adverse side effects continues to dictate the benefit-risk balance of cancer therapy, guiding clinical decision making. As such, the targeting of cancer testis antigens (CTAs) offers exciting new opportunities for therapeutic intervention of cancer since they display highly tumor specific expression patterns, natural immunogenicity and play pivotal roles in various biological processes that are critical for tumor cellular fitness. In this review, we delve deeper into how CTAs contribute to the regulation and maintenance of genomic integrity in cancer, and how these mechanisms can be exploited to specifically target and eradicate tumor cells. We review the current clinical trials targeting aforementioned CTAs, highlight promising pre-clinical data and discuss current challenges and future perspectives for future development of CTA-based strategies that exploit tumor genomic instability.
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Project description:IntroductionNeuroblastoma (NB) is the prime cancer of infancy, and accounts for 9% of pediatric cancer deaths. While children diagnosed with clinically stable NB experience a complete cure, those with high-risk disease (HR-NB) do not recover, despite intensive therapeutic strategies. Development of novel and effective targeted therapies is needed to counter disease progression, and to benefit long-term survival of children with HR-NB.Areas coveredRecent studies (2017-2020) pertinent to NB evolution are selectively reviewed to recognize novel and effective therapeutic targets. The prospective and promising therapeutic targets/strategies for HR-NB are categorized into (a) targeting oncogene-like and/or reinforcing tumor suppressor (TS)-like lncRNAs; (b) targeting oncogene-like microRNAs (miRs) and/or mimicking TS-miRs; (c) targets for immunotherapy; (d) targeting epithelial-to-mesenchymal transition and cancer stem cells; (e) novel and beneficial combination approaches; and (f) repurposing drugs and other strategies in development.Expert opinionIt is highly unlikely that agents targeting a single candidate or signaling will be beneficial for an HR-NB cure. We must develop efficient drug deliverables for functional targets, which could be integrated and advance clinical therapy. Fittingly, the looming evidence indicated an aggressive evolution of promising novel and integrative targets, development of efficient drugs, and improvised strategies for HR-NB treatment.
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