Nowadays, conventional medical treatments such as surgery, radiotherapy, and chemotherapy cannot cure all types of cancer. A promising approach to treat solid tumors is the use of tumor-targeting ...peptides to deliver drugs or active agents selectively.
Introducing beneficial therapeutic approaches, such as therapeutic peptides and their varied methods of action against tumor cells, can aid researchers in the discovery of novel peptides for cancer treatment. The biomedical applications of therapeutic peptides are highly interesting. These peptides, owing to their high selectivity, specificity, small dimensions, high biocompatibility, and easy modification, provide good opportunities for targeted drug delivery. In recent years, peptides have shown considerable promise as therapeutics or targeting ligands in cancer research and nanotechnology.
This study reviews a variety of therapeutic peptides and targeting ligands in cancer therapy. Initially, three types of tumor-homing and cell-penetrating peptides (CPPs) are described, and then their applications in breast, glioma, colorectal, and melanoma cancer research are discussed.
Cancer stem cells (CSCs) as a small subpopulation in tumor bulk are believed to initiate tumor formation and are responsible for the resistance to cancer therapy. The proliferation and ...differentiation of CSCs result in heterogeneity in a tumor which increases the chance of tumor survival and invasion. Many signaling pathways are abnormally activated or repressed in CSCs. Understanding these pathways and the metabolisms in CSCs may help targeted therapy in drug-resistant tumors. The PI3K/Akt/mTOR pathway is one of the major signaling pathways in CSCs involved in the maintenance of stemness, proliferation, differentiation, epithelial to mesenchymal transition (EMT), migration, and autophagy. Thus, suppressing the PI3K/Akt/mTOR pathway with inhibitors might be a promising strategy for targeted cancer therapy. Although the pathway is well-recognized and reviewed in tumor bulks, the functions in CSCs have not been well focused. Here, we reviewed the PI3K/Akt/mTOR signaling pathway and its functions in CSCs and addressed the potential therapeutic applications in drug-resistant tumors.
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Abstract
Melanoma is the most aggressive form of skin cancer resulting from genetic mutations in melanocytes. Several factors have been considered to be involved in melanoma progression, including ...genetic alteration, processes of damaged DNA repair, and changes in mechanisms of cell growth and proliferation. Epigenetics is the other factor with a crucial role in melanoma development. Epigenetic changes have become novel targets for treating patients suffering from melanoma. These changes can alter the expression of microRNAs and their interaction with target genes, which involves cell growth, differentiation, or even death. Given these circumstances, we conducted the present review to discuss the melanoma risk factors and represent the current knowledge about the factors related to its etiopathogenesis. Moreover, various epigenetic pathways, which are involved in melanoma progression, treatment, and chemo-resistance, as well as employed epigenetic factors as a solution to the problems, will be discussed in detail.
Autoimmune diseases (ADs) could occur due to infectious diseases and vaccination programs. Since millions of people are expected to be infected with SARS-CoV-2 and vaccinated against it, autoimmune ...consequences seem inevitable. Therefore, we have investigated the whole proteome of the SARS-CoV-2 for its ability to trigger ADs. In this regard, the entire proteome of the SARS-CoV-2 was chopped into more than 48000 peptides. The produced peptides were searched against the entire human proteome to find shared peptides with similar experimentally confirmed T-cell and B-cell epitopes. The obtained peptides were checked for their ability to bind to HLA molecules. The possible population coverage was calculated for the most potent peptides. The obtained results indicated that the SARS-CoV-2 and human proteomes share 23 peptides originated from ORF1ab polyprotein, nonstructural protein NS7a, Surface glycoprotein, and Envelope protein of SARS-CoV-2. Among these peptides, 21 peptides had experimentally confirmed equivalent epitopes. Amongst, only nine peptides were predicted to bind to HLAs with known global allele frequency data, and three peptides were able to bind to experimentally confirmed HLAs of equivalent epitopes. Given the HLAs which have already been reported to be associated with ADs, the ESGLKTIL, RYPANSIV, NVAITRAK, and RRARSVAS were determined to be the most harmful peptides of the SARS-CoV-2 proteome. It would be expected that the COVID-19 pandemic and the vaccination against this pathogen could significantly increase the ADs incidences, especially in populations harboring HLA-B*08:01, HLA-A*024:02, HLA-A*11:01 and HLA-B*27:05. The Southeast Asia, East Asia, and Oceania are at higher risk of AD development.
Glioblastoma belongs to the most aggressive type of cancer with a low survival rate that is characterized by the ability in forming a highly immunosuppressive tumor microenvironment. Intercellular ...communication are created via exosomes in the tumor microenvironment through the transport of various biomolecules. They are primarily involved in tumor growth, differentiation, metastasis, and chemotherapy or radiation resistance. Recently several studies have highlighted the critical role of tumor-derived exosomes against immune cells. According to the structural and functional properties, exosomes could be essential instruments to gain a better molecular mechanism for tumor understanding. Additionally, they are qualified as diagnostic/prognostic markers and therapeutic tools for specific targeting of invasive tumor cells such as glioblastomas. Due to the strong dependency of exosome features on the original cells and their developmental status, it is essential to review their critical modulating molecules, clinical relevance to glioma, and associated signaling pathways. This review is a non-clinical study, as the possible role of exosomes and exosomal microRNAs in glioma cancer are reported. In addition, their content to overcome cancer resistance and their potential as diagnostic biomarkers are analyzed.
Neuroblastoma is a common inflammatory-related cancer during infancy. Standard treatment modalities including surgical interventions, high-dose chemotherapy, radiotherapy, and immunotherapy are not ...able to increase survival rate and reduce tumor relapse in high-risk patients. Mesenchymal stem cells (MSCs) are known for their tumor-targeting and immunomodulating properties. MSCs could be engineered to express anticancer agents (i.e., growth factors, cytokines, pro-apoptotic agents) or deliver oncolytic viruses in the tumor microenvironment. As many functions of MSCs are mediated through their secretome, researchers have tried to use extracellular vesicles (EVs) from MSCs for targeted therapy of neuroblastoma. Here, we reviewed the studies to figure out whether the use of MSCs could be worthwhile in neuroblastoma therapy or not. Native MSCs have shown a promoting or inhibiting role in cancers including neuroblastoma. Therefore, MSCs are proposed as a vehicle to deliver anticancer agents such as oncolytic viruses to the neuroblastoma tumor microenvironment. Although modified MSCs or their EVs have been shown to suppress the tumorigenesis of neuroblastoma, further pre-clinical and clinical studies are required to come to a conclusion.
Mesenchymal stem cells (MSCs), modified MSCs, and MSC-derived extracellular vesicles (EVs) could inhibit the tumorigenesis of neuroblastoma and induce apoptosis. Display omitted
•Neuroblastoma is a common cancer during infancy.•Native MSCs have a dual role on neuroblastoma.•MSCs could deliver anticancer agents to neuroblastoma site.•MSCs could be engineered to increase their anticancer activity on neuroblastoma.•Modified MSC-derived exosomes have shown promising in neuroblastoma therapy.
Breast tumor is heterogeneous cancer with high morbidity and mortality rates, particularly in developing countries. Despite new efforts to reduce the breast cancer implications, the number of newly ...diagnosed cases is increasing worldwide. It is believed that cancer stem cells (CSCs) are responsible for the implication of cancers including breast cancer. Although CSCs compose a small population in tumor bulks, they play a crucial role in tumor initiation, progression, metastasis, and chemotherapeutic resistance. These events are mediated by the hypoxia-inducible factor (HIF) pathway which regulates the transcription of genes involved in CSC maintenance and tumorigenesis. In this review, we discussed the mechanisms by which hypoxia- or chemotherapy-induced HIFs promote breast CSC specification.
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•Cancer stem cells (CSCs) are responsible for tumorigenesis and drug resistance.•Hypoxia plays a key role in breast CSC specification.•Hypoxia induces the HIF pathway to induce the expression of pluripotency markers.•HIFs mediate the functions by inducing several target genes.•HIFs and their targets could be considered as therapeutic targets for cancer therapy.
The PI3K/Akt/mTOR signaling pathway is responsible for many cellular behaviors, including survival, growth, and proliferation. A newly identified RNA, circular RNA (circRNA), plays a crucial role in ...the regulation of gene expression. The upregulation of the PI3K/Akt pathway through dysregulated circRNAs promotes breast tumor initiation, growth, and progression. The dysregulation of PI3K/Akt-regulating circRNAs seems to be directly correlated with breast cancer clinical features, including overall survival, tumor size, cancer stage, and lymph node metastasis. In addition, targeting these circRNAs may be a promising option in cancer-targeted therapy. Understanding the molecular pathogenesis of the circRNA-PI3K/AKT axis may give the insight to develop new therapeutic and diagnostic approaches for breast cancer therapy. Here we reviewed the expression and functions of PI3K/AKT-regulating circRNAs, and their correlation with breast cancer clinical features. In addition, the potential of PI3K/AKT-regulating circRNAs as diagnostic/prognostic biomarkers or therapeutic targets was discussed.
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Mesenchymal stem cells (MSCs) have the ability to migrate into tumor sites and release growth factors to modulate the tumor microenvironment. MSC therapy have shown a dual role in cancers, promoting ...or inhibiting. However, MSCs could be used as a carrier of anticancer agents for targeted tumor therapy. Recent technical improvements also allow engineering MSCs to improve tumor-targeting properties, protect anticancer agents, and decrease the cytotoxicity of drugs. While some of MSC functions are mediated through their secretome, MSCs-derived extracellular vesicles (EVs) are also proposed as a possible viechle for cancer therapy. EVs allow efficient loading of anticancer agents and have an intrinsic ability to target tumor cells, making them suitable for targeted therapy of tumors. In addition, the specificity and selectivity of EVs to the tumor sites could be enhanced by surface modification. In this review, we addressed the current approaches used for engineering MSCs and EVs to effectively target tumor sites and deliver anticancer agents.
Graphical abstract. Engineering MSCs and their EVs to target and destroy tumors. MSC: mesenchymal stem cell, EVs: Extracellular vesicles, miRNA: microRNA. Display omitted
Possible models in ecDNA genesis and ecDNA effects in cancer. A) Episome Model, B) Translocation-excision-deletion-amplification Model, C) Chromothripsis Model, D) Multistep evolutionary process ...Model, E) ecDNA unique chromatin architecture(nucleosomal decompation), F) and its unique 3D topology (circular) increase oncogene amplification and transcription, which eventually leads to tumor progression, G) ecDNA has different drug resistance genes (e.g. DHFR, MDR1, MDM2) which make cancer resistant to various drugs, H) ecDNA genomic rearrangement, I) and its uneven segregation between daughter cells, leads to tumor heterogeneity and creation of genetically different subclones which ultimately cause tumor adaptation to the microenvironment stresses and various therapies like radiotherapy, chemotherapy and etc.
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•ecDNAs are acentromeric circular DNA with various oncogenes and drug resistance genes.•Different mechanisms such as episome have been proposed in the genesis of ecDNA.•ecDNAs have enhancer Hijacking which promote oncogenes amplification.•Due to uneven segregation, unique chromatin architecture, they are tumorigenic.•ecDNAs leading to cancer progression and tumor microenvironment heterogeneity.
Cancer can be caused by various factors, including the malfunction of tumor suppressor genes and the hyper-activation of proto-oncogenes. Tumor-associated extrachromosomal circular DNA (eccDNA) has been shown to adversely affect human health and accelerate malignant actions. Whole-genome sequencing (WGS) on different cancer types suggested that the amplification of ecDNA has increased the oncogene copy number in various cancers. The unique structure and function of ecDNA, its profound significance in cancer, and its help in the comprehension of current cancer genome maps, renders it as a hotspot to explore the tumor pathogenesis and evolution. Illumination of the basic mechanisms of ecDNA may provide more insights into cancer therapeutics. Despite the recent advances, different features of ecDNA require further elucidation. In the present review, we primarily discussed the characteristics, biogenesis, genesis, and origin of ecDNA and later highlighted its functions in both tumorigenesis and therapeutic resistance of different cancers.
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