Annalaura Montella, Sueva Cantalupo, Giuseppe D’alterio, Vincenzo Damiano, A. Iolascon, Mario Capasso
{"title":"Improving single nucleotide polymorphisms genotyping accuracy for dihydropyrimidine dehydrogenase testing in pharmacogenetics","authors":"Annalaura Montella, Sueva Cantalupo, Giuseppe D’alterio, Vincenzo Damiano, A. Iolascon, Mario Capasso","doi":"10.37349/etat.2024.00223","DOIUrl":"https://doi.org/10.37349/etat.2024.00223","url":null,"abstract":"Fluoropyrimidines, crucial in cancer treatment, often cause toxicity concerns even at standard doses. Toxic accumulation of fluoropyrimidine metabolites, culminating in adverse effects, can stem from impaired dihydropyrimidine dehydrogenase (DPYD) enzymatic function. Emerging evidence underscores the role of single nucleotide polymorphisms (SNPs) in DPYD gene, capable of inducing DPYD activity deficiency. Consequently, DPYD genotyping’s importance is on the rise in clinical practice before initiating fluoropyrimidine treatment. Although polymerase chain reaction (PCR) followed by Sanger sequencing (SS; PCR-SS) is a prevalent method for DPYD genotyping, it may encounter limitations. In this context, there is reported a case in which a routine PCR-SS approach for genotyping DPYD SNP rs55886062 failed in a proband of African descent. The Clinical Pharmacogenetics Implementation Consortium (CPIC) categorizes the guanine (G) allele of this SNP as non-functional. The enforcement of whole genome sequencing (WGS) approach led to the identification of two adenine (A) insertions near the PCR primers annealing regions in the proband, responsible for a sequence frameshift and a genotyping error for rs55886062. These SNPs (rs145228578, 1-97981199-T-TA and rs141050810, 1-97981622-G-GA) were extremely rare in non-Finnish Europeans (0.05%) but prevalent in African populations (16%). Although limited evidence was available for these SNPs, they were catalogued as benign variants in public databases. Notably, these two SNPs exhibited a high linkage disequilibrium [LD; squared correlation coefficient (R2) = 0.98]. These findings highlighted the importance to consider the prevalence of genetic variants within diverse ethnic populations when designing primers and probes for SNP genotyping in pharmacogenetic testing. This preventive measure is essential to avoid sequence frameshifts or primer misalignments arising from SNP occurrences in the genome, which can compromise PCR-SS and lead to genotyping failures. Furthermore, this case highlights the significance of exploring alternative genotyping approaches, like WGS, when confronted with challenges associated with conventional techniques.","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"52 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140660658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Jeeyavudeen, Navin Mathiyalagan, Cornelius Fernandez James, Joseph M Pappachan
{"title":"Tumor metabolism in pheochromocytomas: clinical and therapeutic implications","authors":"M. Jeeyavudeen, Navin Mathiyalagan, Cornelius Fernandez James, Joseph M Pappachan","doi":"10.37349/etat.2024.00222","DOIUrl":"https://doi.org/10.37349/etat.2024.00222","url":null,"abstract":"Pheochromocytomas and paragangliomas (PPGLs) have emerged as one of the most common endocrine tumors. It epitomizes fascinating crossroads of genetic, metabolic, and endocrine oncology, providing a canvas to explore the molecular intricacies of tumor biology. Predominantly rooted in the aberration of metabolic pathways, particularly the Krebs cycle and related enzymatic functionalities, PPGLs manifest an intriguing metabolic profile, highlighting elevated levels of oncometabolites like succinate and fumarate, and furthering cellular malignancy and genomic instability. This comprehensive review aims to delineate the multifaceted aspects of tumor metabolism in PPGLs, encapsulating genetic factors, oncometabolites, and potential therapeutic avenues, thereby providing a cohesive understanding of metabolic disturbances and their ramifications in tumorigenesis and disease progression. Initial investigations into PPGLs metabolomics unveiled a stark correlation between specific genetic mutations, notably in the succinate dehydrogenase complex (SDHx) genes, and the accumulation of oncometabolites, establishing a pivotal role in epigenetic alterations and hypoxia-inducible pathways. By scrutinizing voluminous metabolic studies and exploiting technologies, novel insights into the metabolic and genetic aspects of PPGLs are perpetually being gathered elucidating complex interactions and molecular machinations. Additionally, the exploration of therapeutic strategies targeting metabolic abnormalities has burgeoned harboring potential for innovative and efficacious treatment modalities. This review encapsulates the profound metabolic complexities of PPGLs, aiming to foster an enriched understanding and pave the way for future investigations and therapeutic innovations in managing these metabolically unique tumors.","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"4 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140661863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
James Michael Verner, Harry Frederick Arbuthnott, Raghavskandhan Ramachandran, Manini Bharadwaj, Natasha Chaudhury, E. Jou
{"title":"Emerging roles of type 1 innate lymphoid cells in tumour pathogenesis and cancer immunotherapy","authors":"James Michael Verner, Harry Frederick Arbuthnott, Raghavskandhan Ramachandran, Manini Bharadwaj, Natasha Chaudhury, E. Jou","doi":"10.37349/etat.2023.00219","DOIUrl":"https://doi.org/10.37349/etat.2023.00219","url":null,"abstract":"Innate lymphoid cells (ILCs) are the most recently discovered class of innate immune cells found to have prominent roles in various human immune-related pathologies such as infection and autoimmune diseases. However, their role in cancer was largely unclear until recently, where several emerging studies over the past few years unanimously demonstrate ILCs to be critical players in tumour immunity. Being the innate counterpart of T cells, ILCs are potent cytokine producers through which they orchestrate the overall immune response upstream of adaptive immunity thereby modulating T cell function. Out of the major ILC subsets, ILC1s have gained significant traction as potential immunotherapeutic candidates due to their central involvement with the anti-tumour type 1 immune response. ILC1s are potent producers of the well-established anti-tumour cytokine interferon γ (IFNγ), and exert direct cytotoxicity against cancer cells in response to the cytokine interleukin-15 (IL-15). However, in advanced diseases, ILC1s are found to demonstrate an exhausted phenotype in the tumour microenvironment (TME) with impaired effector functions, characterised by decreased responsiveness to cytokines and reduced IFNγ production. Tumour cells produce immunomodulatory cytokines such as transforming growth factor β (TGFβ) and IL-23, and through these suppress ILC1 anti-tumour actfivities and converts ILC1s to pro-tumoural ILC3s respectively, resulting in disease progression. This review provides a comprehensive overview of ILC1s in tumour immunity, and discusses the exciting prospects of harnessing ILC1s for cancer immunotherapy, either alone or in combination with cytokine-based treatment. The exciting prospects of targeting the upstream innate immune system through ILC1s may surmount the limitations associated with adaptive immune T cell-based strategies used in the clinic currently, and overcome cancer immunotherapeutic resistance.","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"142 28","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140668650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Artificial intelligence and classification of mature lymphoid neoplasms","authors":"J. Carreras, R. Hamoudi, Naoya Nakamura","doi":"10.37349/etat.2024.00221","DOIUrl":"https://doi.org/10.37349/etat.2024.00221","url":null,"abstract":"Hematologists, geneticists, and clinicians came to a multidisciplinary agreement on the classification of lymphoid neoplasms that combines clinical features, histological characteristics, immunophenotype, and molecular pathology analyses. The current classification includes the World Health Organization (WHO) Classification of tumours of haematopoietic and lymphoid tissues revised 4th edition, the International Consensus Classification (ICC) of mature lymphoid neoplasms (report from the Clinical Advisory Committee 2022), and the 5th edition of the proposed WHO Classification of haematolymphoid tumours (lymphoid neoplasms, WHO-HAEM5). This article revises the recent advances in the classification of mature lymphoid neoplasms. Artificial intelligence (AI) has advanced rapidly recently, and its role in medicine is becoming more important as AI integrates computer science and datasets to make predictions or classifications based on complex input data. Summarizing previous research, it is described how several machine learning and neural networks can predict the prognosis of the patients, and classified mature B-cell neoplasms. In addition, new analysis predicted lymphoma subtypes using cell-of-origin markers that hematopathologists use in the clinical routine, including CD3, CD5, CD19, CD79A, MS4A1 (CD20), MME (CD10), BCL6, IRF4 (MUM-1), BCL2, SOX11, MNDA, and FCRL4 (IRTA1). In conclusion, although most categories are similar in both classifications, there are also conceptual differences and differences in the diagnostic criteria for some diseases. It is expected that AI will be incorporated into the lymphoma classification as another bioinformatics tool.","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"29 25","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140672449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Magnetite nanoparticles: an emerging adjunctive tool for the improvement of cancer immunotherapy","authors":"Phoomipat Jungcharoen, Kunakorn Thivakorakot, Nachayada Thientanukij, Natkamon Kosachunhanun, Chayanittha Vichapattana, Jutatip Panaampon, Charupong Saengboonmee","doi":"10.37349/etat.2024.00220","DOIUrl":"https://doi.org/10.37349/etat.2024.00220","url":null,"abstract":"Cancer immunotherapy has emerged as a groundbreaking field, offering promising and transformative tools for oncological research and treatment. However, it faces several limitations, including variations in cancer types, dependence on the tumor microenvironments (TMEs), immune cell exhaustion, and adverse reactions. Magnetic nanoparticles, particularly magnetite nanoparticles (MNPs), with established pharmacodynamics and pharmacokinetics for clinical use, hold great promise in this context and are now being explored for therapeutic aims. Numerous preclinical studies have illustrated their efficacy in enhancing immunotherapy through various strategies, such as modulating leukocyte functions, creating favorable TMEs for cytotoxic T lymphocytes, combining with monoclonal antibodies, and stimulating the immune response via magnetic hyperthermia (MHT) treatment (Front Immunol. 2021;12:701485. doi: 10.3389/fimmu.2021.701485). However, the current clinical trials of MNPs are mostly for diagnostic aims and as a tool for generating hyperthermia for tumor ablation. With concerns about the adverse effects of MNPs in the in vivo systems, clinical translation and clinical study of MNP-boosted immunotherapy remains limited. The lack of extensive clinical investigations poses a current barrier to patient application. Urgent efforts are needed to ascertain both the efficacy of MNP-enhanced immunotherapy and its safety profile in combination therapy. This article reviews the roles, potential, and challenges of using MNPs in advancing cancer immunotherapy. The application of MNPs in boosting immunotherapy, and its perspective role in research and development is also discussed.","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"61 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140670726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thomas Hansen, Jonathon Hill, Gary Tincknell, Derrick Siu, Daniel Brungs, Philip Clingan, Lorraine Chantrill, Udit Nindra
{"title":"Evidence for the evolving role of neoadjuvant and perioperative immunotherapy in resectable non-small cell lung cancer.","authors":"Thomas Hansen, Jonathon Hill, Gary Tincknell, Derrick Siu, Daniel Brungs, Philip Clingan, Lorraine Chantrill, Udit Nindra","doi":"10.37349/etat.2024.00273","DOIUrl":"10.37349/etat.2024.00273","url":null,"abstract":"<p><p>The treatment of early-stage non-small cell lung cancer (NSCLC) is becoming increasingly complex. Standard of care management for the past decade has been adjuvant chemotherapy following curative intent resection regardless of nodal status or tumour profile. With the increased incorporation of immunotherapy in NSCLC, especially in the locally advanced, unresectable, or metastatic settings, multiple studies have sought to assess its utility in early-stage disease. While there are suboptimal responses to neoadjuvant chemotherapy alone, there is a strong rationale for the use of neoadjuvant immunotherapy in tumour downstaging, based upon the concept of enhanced T cell priming at the time of a high tumour antigen burden, and demonstrated clinically in other solid tumours, such as melanoma. In the NSCLC cancer setting, currently over 20 combinations of chemoimmunotherapy in the neoadjuvant and perioperative setting have been studied with results variable. Multiple large phase III studies have demonstrated that neoadjuvant chemoimmunotherapy combinations result in significant advances in pathological response, disease free and overall survival which has led to practice change across the world. Currently, combination immunotherapy regimens with novel agents targeting alternate immunomodulatory pathways are now being investigated. Given this, the landscape of treatment in resectable early-stage NSCLC has become increasingly complex. This review outlines the literature of neoadjuvant and perioperative immunotherapy and discusses its potential benefits and complexities and ongoing considerations into future research.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 6","pages":"1247-1260"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Min Woo Hwang, Jasmine Kauffeld, Sarah Belay, Joep J de Jong, Elai Davicioni, Wenping Li, Jeanny B Aragon-Ching
{"title":"Upper tract urothelial cancer (UTUC) genomic profiling and correlation regarding benefit of platinum-based chemotherapy.","authors":"Min Woo Hwang, Jasmine Kauffeld, Sarah Belay, Joep J de Jong, Elai Davicioni, Wenping Li, Jeanny B Aragon-Ching","doi":"10.37349/etat.2024.00274","DOIUrl":"10.37349/etat.2024.00274","url":null,"abstract":"<p><p>Upper tract urothelial cancer (UTUC) are rare subsets of urothelial cancer, which typically present with more aggressive course. Molecular markers stratifying urothelial tumors as luminal subtype and non-luminal subtype tumors have been proposed to select patients who may have greater or lesser benefit from neoadjuvant systemic therapy in bladder cancer, though not yet evaluated in UTUC. Here, a single-institution study retrospectively obtained clinical and genomic information in patients with UTUC and evaluated four patient tumors using the Decipher Bladder<sup>®</sup> assay and Foundation Medicine<sup>®</sup> test. All four patients had non-luminal molecular subtype including basal (<i>N</i> = 4) and mixed basal/claudin-low (<i>N</i> = 2) subtypes. The best clinical response achieved was stable disease in a patient who had basal/claudin-low subtype with residual ypT3 after neoadjuvant chemotherapy. For the remaining three patients, all were treated with platinum-based chemotherapy for eventual metastatic disease but all three showed progressive disease with limited overall survival, highlighting their aggressive course. The non-luminal subtype and lack of <i>FGFR</i> alteration may partly explain the poor overall outcomes while the real-world benefit of next generation sequencing for clinical use in UTUC patients require further clarification in a larger cohort study.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 6","pages":"1261-1270"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Apurva Sood, V V Jothiswaran, Amrita Singh, Anuradha Sharma
{"title":"Anticancer peptides as novel immunomodulatory therapeutic candidates for cancer treatment.","authors":"Apurva Sood, V V Jothiswaran, Amrita Singh, Anuradha Sharma","doi":"10.37349/etat.2024.00264","DOIUrl":"10.37349/etat.2024.00264","url":null,"abstract":"<p><p>Cancer remains a concern after years of research in this field. Conventional therapies such as chemotherapy, radiation, and surgery are available for cancer treatment, but they are characterized by various side effects. There are several immunological challenges that make it difficult for the immune system and conventional therapies to treat cancer. Some of these challenges include heterogeneity, resistance to medicines, and cancer relapse. Even advanced treatments like immune checkpoint inhibitors (ICIs), which revolutionized cancer treatment, have associated toxicity and resistance further necessitate the exploration of alternative therapies. Anticancer peptides (ACPs) offer promising potential as cancer-fighting agents and address challenges such as treatment resistance, tumor heterogeneity, and metastasis. Although these peptides exist as components of the defense system in various plants, animals, fungi, etc., but can also be created synthetically and used as a new treatment measure. These peptides possess properties that make them appealing for cancer therapy, such as apoptosis induction, inhibition of angiogenesis, and cell membrane breakdown with low toxicity. Their capacity to specifically target cancer cells selectively holds promise for enhancing treatment environments as well as improving patients' quality of life. This review provides detailed insights into the different prospects of ACPs, including their characterization, use as immunomodulatory agents in cancer treatment, and their mechanistic details after addressing various immunological challenges in existing cancer treatment strategies. In conclusion, ACPs have promising potential as novel cancer therapeutics due to their target specificity and fewer side effects than conventional therapies.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 5","pages":"1074-1099"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Scott D Bell, Anthony E Quinn, Tom D Spitzer, Brady B Voss, Mark R Wakefield, Yujiang Fang
{"title":"Emerging molecular therapies in the treatment of bladder cancer.","authors":"Scott D Bell, Anthony E Quinn, Tom D Spitzer, Brady B Voss, Mark R Wakefield, Yujiang Fang","doi":"10.37349/etat.2024.00267","DOIUrl":"10.37349/etat.2024.00267","url":null,"abstract":"<p><p>Bladder cancer is a leading cancer type in men. The complexity of treatment in late-stage bladder cancer after systemic spread through the lymphatic system highlights the importance of modulating disease-free progression as early as possible in cancer staging. With current therapies relying on previous standards, such as platinum-based chemotherapeutics and immunomodulation with Bacillus Calmette-Guerin, researchers, and clinicians are looking for targeted therapies to stop bladder cancer at its source early in progression. A new era of molecular therapies that target specific features upregulated in bladder cancer cell lines is surfacing, which may be able to provide clinicians and patients with better control of disease progression. Here, we discuss multiple emerging therapies including immune checkpoint inhibitors of the programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway, antibody-drug conjugates, modulation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) cell proliferation pathway, chimeric antigen receptor T-cell therapy, and fibroblast growth factor receptor targeting. Together, these modern treatments provide potentially promising results for bladder cancer patients with the possibility of increasing remission and survival rates.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 5","pages":"1135-1154"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Prospects for breast cancer immunotherapy using microRNAs and transposable elements as objects.","authors":"Rustam Nailevich Mustafin","doi":"10.37349/etat.2024.00261","DOIUrl":"10.37349/etat.2024.00261","url":null,"abstract":"<p><p>One of the directions in treatment of chemoresistant breast cancer (BC) may include new methods of activating the immune response against tumor cells. Clinically used checkpoint inhibition using antibodies to PD-1 and PD-L1 works in some patients, but the lack of biomarkers means number of respondents is low. The possibility of combining this method with chemotherapy is limited by an increased risk of toxic liver damage, development of immune-related pneumonitis, and thyroid dysfunction. This article includes introduction into the clinic of new methods of immunotherapy for BC, among which epigenetic activation of retroelements, double-stranded transcripts of which stimulate the interferon response against the tumor, is promising. For this purpose, inhibitors of DNA methyltransferase*, histone deacetylase* and histone methyltransferase* are used (* subtitles in the main text). Their antitumor effect is also mediated by removal of repressive epigenetic marks from tumor suppressor genes. However, numerous studies have proven the role of retroelements in the carcinogenesis of various malignant neoplasms, including BC. Moreover, endogenous retroviruses HERV-K and LINE1 retrotransposons are planned to be used as diagnostic biomarkers for BC. Therefore, a rational approach to using viral mimicry in antitumor therapy of BC may be the simultaneous suppression of specific retrotransposons (drivers for carcinogenesis) using reverse transcriptase inhibitors and silencing of specific transposons involved in carcinogenesis using complementary microRNAs. To determine possible pathways of influence in this direction, 35 specific transposon-derived microRNAs* changes in BC were identified, which can become guides for targeted therapy of BC.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"5 5","pages":"1011-1026"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}