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Advances in Cancer Research 2014Therapeutic cancer vaccines have the potential of being integrated in the therapy of numerous cancer types and stages. The wide spectrum of vaccine platforms and vaccine... (Review)
Review
Therapeutic cancer vaccines have the potential of being integrated in the therapy of numerous cancer types and stages. The wide spectrum of vaccine platforms and vaccine targets is reviewed along with the potential for development of vaccines to target cancer cell "stemness," the epithelial-to-mesenchymal transition (EMT) phenotype, and drug-resistant populations. Preclinical and recent clinical studies are now revealing how vaccines can optimally be used with other immune-based therapies such as checkpoint inhibitors, and so-called nonimmune-based therapeutics, radiation, hormonal therapy, and certain small molecule targeted therapies; it is now being revealed that many of these traditional therapies can lyse tumor cells in a manner as to further potentiate the host immune response, alter the phenotype of nonlysed tumor cells to render them more susceptible to T-cell lysis, and/or shift the balance of effector:regulatory cells in a manner to enhance vaccine efficacy. The importance of the tumor microenvironment, the appropriate patient population, and clinical trial endpoints is also discussed in the context of optimizing patient benefit from vaccine-mediated therapy.
Topics: Animals; Biomarkers, Tumor; Cancer Vaccines; Clinical Trials as Topic; Combined Modality Therapy; Disease Progression; Drug Resistance, Neoplasm; Humans; Molecular Targeted Therapy; Neoplasms
PubMed: 24889529
DOI: 10.1016/B978-0-12-800249-0.00002-0 -
Oncology Research 2023Cancer immunotherapy has emerged as a promising strategy for the treatment of cancer, with the tumor microenvironment (TME) playing a pivotal role in modulating the... (Review)
Review
Cancer immunotherapy has emerged as a promising strategy for the treatment of cancer, with the tumor microenvironment (TME) playing a pivotal role in modulating the immune response. CD47, a cell surface protein, has been identified as a crucial regulator of the TME and a potential therapeutic target for cancer therapy. However, the precise functions and implications of CD47 in the TME during immunotherapy for cancer patients remain incompletely understood. This comprehensive review aims to provide an overview of CD47's multifaced role in TME regulation and immune evasion, elucidating its impact on various types of immunotherapy outcomes, including checkpoint inhibitors and CAR T-cell therapy. Notably, CD47-targeted therapies offer a promising avenue for improving cancer treatment outcomes, especially when combined with other immunotherapeutic approaches. The review also discusses current and potential CD47-targeted therapies being explored for cancer treatment and delves into the associated challenges and opportunities inherent in targeting CD47. Despite the demonstrated effectiveness of CD47-targeted therapies, there are potential problems, including unintended effects on healthy cells, hematological toxicities, and the development if resistance. Consequently, further research efforts are warranted to fully understand the underlying mechanisms of resistance and to optimize CD47-targeted therapies through innovative combination approaches, ultimately improving cancer treatment outcomes. Overall, this comprehensive review highlights the significance of CD47 as a promising target for cancer immunotherapy and provides valuable insight into the challenges and opportunities in developing effective CD47-targeted therapies for cancer treatment.
Topics: Humans; CD47 Antigen; Immunotherapy; Membrane Proteins; Tumor Microenvironment; Neoplasms
PubMed: 38188674
DOI: 10.32604/or.2023.042383 -
Journal of Hepatology Dec 2021Hepatic encephalopathy (HE) is a complication of cirrhosis characterised by neuropsychiatric and motor dysfunction. Microbiota-host interactions play an important role... (Review)
Review
Hepatic encephalopathy (HE) is a complication of cirrhosis characterised by neuropsychiatric and motor dysfunction. Microbiota-host interactions play an important role in HE pathogenesis. Therapies targeting microbial community composition and function have been explored for the treatment of HE. Prebiotics, probiotics and faecal microbiota transplant (FMT) have been used with the aim of increasing the abundance of potentially beneficial taxa, while antibiotics have been used to decrease the abundance of potentially harmful taxa. Other microbiome therapeutics, including postbiotics and absorbents, have been used to target microbial products. Microbiome-targeted therapies for HE have had some success, notably lactulose and rifaximin, with probiotics and FMT also showing promise. However, there remain several challenges to the effective application of microbiome therapeutics in HE, including the resilience of the microbiome to sustainable change and unpredictable clinical outcomes from microbiota alterations. Future work in this space should focus on rigorous trial design, microbiome therapy selection, and a personalised approach to HE.
Topics: Fecal Microbiota Transplantation; Hepatic Encephalopathy; Host Microbial Interactions; Humans; Microbiota; Prebiotics; Probiotics
PubMed: 34453966
DOI: 10.1016/j.jhep.2021.08.004 -
Oncotarget Jan 2017Gynecological cancers are known for being very aggressive at their advanced stages. Indeed, the survival rate of both ovarian and endometrial cancers is very low when... (Review)
Review
Gynecological cancers are known for being very aggressive at their advanced stages. Indeed, the survival rate of both ovarian and endometrial cancers is very low when diagnosed lately and the success rate of current chemotherapy regimens is not very efficient. One of the main reasons for this low success rate is the acquired chemoresistance of these cancers during their progression. The mechanisms responsible for this acquired chemoresistance are numerous, including efflux pumps, repair mechanisms, survival pathways (PI3K/AKT, MAPK, EGFR, mTOR, estrogen signaling) and tumor suppressors (P53 and Par-4). To overcome these resistances, a new type of therapy has emerged named targeted therapy. The principle of targeted therapy is simple, taking advantage of changes acquired in malignant cancer cells (receptors, proteins, mechanisms) by using compounds specifically targeting these, thus limiting their action on healthy cells. Targeted therapies are emerging and many clinical trials targeting these pathways, frequently involved in chemoresistance, have been tested on gynecological cancers. Despite some targets being less efficient than expected as mono-therapies, the combination of compounds seems to be the promising avenue. For instance, we demonstrate using ChIP-seq analysis that estrogen downregulate tumor suppressor Par-4 in hormone-dependent cells by directly binding to its DNA regulatory elements and inhibiting estrogen signaling could reinstate Par-4 apoptosis-inducing abilities. This review will focus on the chemoresistance mechanisms and the clinical trials of targeted therapies associated with these, specifically for endometrial and ovarian cancers.
Topics: Antineoplastic Combined Chemotherapy Protocols; Apoptosis Regulatory Proteins; Clinical Trials as Topic; Drug Resistance, Neoplasm; Endometrial Neoplasms; Estrogens; Female; Gene Regulatory Networks; Humans; Molecular Targeted Therapy; Ovarian Neoplasms; Treatment Outcome
PubMed: 28008141
DOI: 10.18632/oncotarget.14021 -
Expert Opinion on Therapeutic Targets Sep 2020Neuroblastoma (NB) is the prime cancer of infancy, and accounts for 9% of pediatric cancer deaths. While children diagnosed with clinically stable NB experience a... (Review)
Review
INTRODUCTION
Neuroblastoma (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 COVERED
Recent 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 OPINION
It 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.
Topics: Animals; Antineoplastic Agents; Child; Disease Progression; Drug Development; Epithelial-Mesenchymal Transition; Humans; Immunotherapy; Infant; Molecular Targeted Therapy; Neoplastic Stem Cells; Neuroblastoma; Survival Rate
PubMed: 33021426
DOI: 10.1080/14728222.2020.1790528 -
Continuum (Minneapolis, Minn.) Dec 2020Management of metastasis to the central nervous system (CNS) has evolved, and molecular characterization of metastatic disease is now routinely done. Targeted therapies,... (Review)
Review
PURPOSE OF REVIEW
Management of metastasis to the central nervous system (CNS) has evolved, and molecular characterization of metastatic disease is now routinely done. Targeted therapies, once few in number with limited penetration into the CNS, have multiplied in number and increased in CNS coverage. This article addresses recent advances in the evaluation and clinical management of patients with CNS metastasis.
RECENT FINDINGS
Metastasis of cancer to the CNS can be diagnosed and characterized with novel techniques, including molecular analyses of the spinal fluid, so-called liquid biopsies. Resected parenchymal CNS metastases are now routinely subjected to genomic sequencing. For patients with CNS metastases displaying targetable mutations, a wide variety of treatment options are available, including deferral of radiation therapy in favor of a trial of an orally bioavailable targeted therapy or immunotherapy. For patients without a molecularly targetable lesion, local treatment in the form of radiation therapy, now most often stereotactic radiosurgery, is supplanting untargeted whole-brain radiation therapy.
SUMMARY
Technologic advances in diagnosis and management have resulted in new diagnostic and therapeutic approaches to patients with metastasis to the CNS, with resulting improvements in progression-free and overall survival.
Topics: Brain Neoplasms; Central Nervous System; Central Nervous System Neoplasms; Cranial Irradiation; Humans; Radiosurgery
PubMed: 33273173
DOI: 10.1212/CON.0000000000000939 -
Viruses Sep 2020Kaposi's sarcoma-associated herpesvirus (KSHV) also known as human herpesvirus 8 (HHV-8), is linked to several human malignancies including Kaposi sarcoma (KS), primary... (Review)
Review
Kaposi's sarcoma-associated herpesvirus (KSHV) also known as human herpesvirus 8 (HHV-8), is linked to several human malignancies including Kaposi sarcoma (KS), primary effusion lymphoma (PEL), multicentric Castleman's disease (MCD) and recently KSHV inflammatory cytokine syndrome (KICS). As with other diseases that have a significant inflammatory component, current therapy for KSHV-associated disease is associated with significant off-target effects. However, recent advances in our understanding of the pathogenesis of KSHV have produced new insight into the use of cytokines as potential therapeutic targets. Better understanding of the role of cytokines during KSHV infection and tumorigenesis may lead to new preventive or therapeutic strategies to limit KSHV spread and improve clinical outcomes. The cytokines that appear to be promising candidates as KSHV antiviral therapies include interleukins 6, 10, and 12 as well as interferons and tumor necrosis factor-family cytokines. This review explores our current understanding of the roles that cytokines play in promoting KSHV infection and tumorigenesis, and summarizes the current use of cytokines as therapeutic targets in KSHV-associated diseases.
Topics: Animals; Castleman Disease; Chemokines; Cytokines; Herpesviridae Infections; Herpesvirus 8, Human; Host-Pathogen Interactions; Humans; Immunomodulation; Lymphoma, Primary Effusion; Sarcoma, Kaposi; Signal Transduction
PubMed: 32998419
DOI: 10.3390/v12101097 -
Journal of Controlled Release :... Dec 2020Chronic and acute kidney disease constitute a worldwide health burden, but are still lacking efficient therapeutics. Current medication such as anti-inflammatory... (Review)
Review
Chronic and acute kidney disease constitute a worldwide health burden, but are still lacking efficient therapeutics. Current medication such as anti-inflammatory steroids causes systemic side effects, and is unable to stop the progression of the disease. Efforts have been devoted towards the development of renal-targeted therapies, however, no such approach has reached the clinic, yet. Here, we critically review the current status of renal-targeted drugs and delivery strategies. Specifically, we focus on the quantitative aspect of delivery by compiling information on kidney-to-liver ratios and also investigating to which degree the implementation of a targeting functionality increases the distribution of the drug to the kidney. As we show, two types of functional outcomes can be distinguished: (i) Targeting to the kidney goes along with an increase in kidney-to-liver ratio. This, we denote as direct targeting; (ii) the accumulation of the drug in the kidney increases, but the kidney-to-liver ratio remains unchanged, thereby the carrier leads to a general uptake enhancement. Overall, the most effective targeting was reached with receptor and transporter directed strategies. Reaching glomerular cells and the avoidance of liver accumulation for nanoparticulate formulations pose the greatest challenges.
Topics: Drug Delivery Systems; Humans; Kidney; Kidney Diseases; Kidney Glomerulus; Pharmaceutical Preparations
PubMed: 32931896
DOI: 10.1016/j.jconrel.2020.09.022 -
International Journal of Molecular... Apr 2020RNA-binding proteins (RBPs) are involved in regulating all aspects of RNA metabolism, including processing, transport, translation, and degradation. Dysregulation of RNA... (Review)
Review
RNA-binding proteins (RBPs) are involved in regulating all aspects of RNA metabolism, including processing, transport, translation, and degradation. Dysregulation of RNA metabolism is linked to a plethora of diseases, such as cancer, neurodegenerative diseases, and neuromuscular disorders. Recent years have seen a dramatic shift in the knowledge base, with RNA increasingly being recognised as an attractive target for precision medicine therapies. In this article, we are going to review current RNA-targeted therapies. Furthermore, we will scrutinise a range of drug discoveries targeting protein-RNA interactions. In particular, we will focus on the interplay between Lin28 and let-7, splicing regulatory proteins and survival motor neuron (SMN) pre-mRNA, as well as HuR, Musashi, proteins and their RNA targets. We will highlight the mechanisms RBPs utilise to modulate RNA metabolism and discuss current high-throughput screening strategies. This review provides evidence that we are entering a new era of RNA-targeted medicine.
Topics: Animals; Biomarkers; Clinical Studies as Topic; Drug Discovery; Drug Evaluation, Preclinical; Genetic Therapy; High-Throughput Screening Assays; Humans; Molecular Targeted Therapy; RNA; RNA Interference; RNA-Binding Proteins; Targeted Gene Repair; Treatment Outcome
PubMed: 32340368
DOI: 10.3390/ijms21082996 -
Signal Transduction and Targeted Therapy Mar 2020The incidence of lymphoma has gradually increased over previous decades, and it ranks among the ten most prevalent cancers worldwide. With the development of targeted... (Review)
Review
The incidence of lymphoma has gradually increased over previous decades, and it ranks among the ten most prevalent cancers worldwide. With the development of targeted therapeutic strategies, though a subset of lymphoma patients has become curable, the treatment of refractory and relapsed diseases remains challenging. Many efforts have been made to explore new targets and to develop corresponding therapies. In addition to novel antibodies targeting surface antigens and small molecular inhibitors targeting oncogenic signaling pathways and tumor suppressors, immune checkpoint inhibitors and chimeric antigen receptor T-cells have been rapidly developed to target the tumor microenvironment. Although these targeted agents have shown great success in treating lymphoma patients, adverse events should be noted. The selection of the most suitable candidates, optimal dosage, and effective combinations warrant further investigation. In this review, we systematically outlined the advances in targeted therapy for malignant lymphoma, providing a clinical rationale for mechanism-based lymphoma treatment in the era of precision medicine.
Topics: Antibodies, Monoclonal; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Humans; Immunotherapy; Lymphoma; Molecular Targeted Therapy; Precision Medicine; Tumor Microenvironment
PubMed: 32296035
DOI: 10.1038/s41392-020-0113-2