Anu Shibi Anilkumar, Sheena Mariam Thomas, Ramakrishnan Veerabathiran
{"title":"Next-generation cancer vaccines: targeting cryptic and non-canonical antigens for precision immunotherapy.","authors":"Anu Shibi Anilkumar, Sheena Mariam Thomas, Ramakrishnan Veerabathiran","doi":"10.37349/etat.2025.1002338","DOIUrl":"10.37349/etat.2025.1002338","url":null,"abstract":"<p><p>Cancer immunotherapy has revolutionized oncology by harnessing the immune system to target tumor cells. Cancer vaccines that trigger immune responses specific to tumors are becoming more and more popular among new approaches. Nevertheless, traditional tumour-associated antigens are susceptible to immune tolerance and frequently show low immunogenicity. The revolutionary potential of cryptic and non-canonical antigens as new targets for precision immunotherapy is examined in this review. Due to their enhanced tumor selectivity and ability to evade central tolerance, these unconventional antigens present encouraging options for vaccine development. This review examines the mechanisms underlying their antigen production, advanced technologies for their discovery, and various vaccine platforms, highlighting their potential to drive the next generation of cancer vaccines.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002338"},"PeriodicalIF":0.0,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12464554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145187770","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}
Mariam Rojas, Malena Manzi, Sergio Madurga, Fernando Enrique García Velásquez, Maira Alejandra Romero, Silvia Marín, Marta Cascante, Joan Maurel
{"title":"Metabolic plasticity drives specific mechanisms of chemotherapy and targeted therapy resistance in metastatic colorectal cancer.","authors":"Mariam Rojas, Malena Manzi, Sergio Madurga, Fernando Enrique García Velásquez, Maira Alejandra Romero, Silvia Marín, Marta Cascante, Joan Maurel","doi":"10.37349/etat.2025.1002337","DOIUrl":"10.37349/etat.2025.1002337","url":null,"abstract":"<p><p>Microsatellite-stable metastatic colorectal cancer (MSS mCRC) is currently treated with chemotherapy and targeted agents based on RAS and BRAF mutational status. Although these therapies offer initial benefit, most patients rapidly develop resistance, with fewer than 20% remaining progression-free at two years. This review aims to synthesize emerging evidence on the metabolic mechanisms driving treatment resistance in MSS mCRC, with a particular focus on the immune-metabolic signature (IMMETCOLS) classification. We conducted a comprehensive review of preclinical models, transcriptomic datasets, and clinical trial results addressing metabolic adaptations to chemotherapy and targeted therapies in MSS mCRC. The IMMETCOLS framework defines three metabolic subtypes-IMC1, IMC2, and IMC3-each associated with distinct resistance mechanisms. IMC1 exhibits glycolysis and transforming growth factor-β (TGF-β)-dependent signaling enriched in inflammatory fibroblasts, conferring resistance to chemotherapy. IMC2 relies on oxidative phosphorylation and glutamine metabolism, supporting antioxidant defenses and resistance to both cytotoxic agents and anti-EGFR therapies. IMC3 demonstrates lactate-fueled respiration and pentose phosphate pathway activation, contributing to redox balance, DNA repair, and resistance to targeted therapies such as anti-BRAF or KRAS inhibitors. All subtypes display metabolic plasticity under therapeutic pressure. Emerging clinical data support tailoring targeted therapy combinations based on IMMETCOLS subtype, particularly in BRAF- and HER2-positive populations. Understanding subtype-specific metabolic rewiring in MSS mCRC offers novel opportunities to overcome drug resistance. Targeting the metabolic vulnerabilities defined by the IMMETCOLS signature may improve response durability and inform precision treatment strategies.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002337"},"PeriodicalIF":0.0,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12464553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145187800","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}
Emmanouil K Verigos, Sofia Sagredou, Kosmas E Verigos, Kyriakos Orfanakos, Constantinos E Alifieris, Maria V Deligiorgi, Panagiotis Dalezis, Mihalis I Panayiotidis, Petros N Karamanakos, Dimitrios T Trafalis
{"title":"Predictive value of 8-hydroxy-2'-deoxyguanosine and 8-nitroguanine production in radiation-induced skin damage after postoperative breast cancer radiotherapy.","authors":"Emmanouil K Verigos, Sofia Sagredou, Kosmas E Verigos, Kyriakos Orfanakos, Constantinos E Alifieris, Maria V Deligiorgi, Panagiotis Dalezis, Mihalis I Panayiotidis, Petros N Karamanakos, Dimitrios T Trafalis","doi":"10.37349/etat.2025.1002336","DOIUrl":"10.37349/etat.2025.1002336","url":null,"abstract":"<p><strong>Aim: </strong>During radiation treatment, reactive oxygen species (ROS) and nitrogen species (RNS) are produced and, by extension, DNA adducts known as 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-nitroguanine (8-NG), respectively. However, one of the most common side effects induced by radiotherapy is skin toxicity, which affects patients' quality of life. In the present study, we aimed to investigate the potential predictive value of 8-OHdG and 8-NG by exploring the correlations between the alterations in the concentration levels of the two lesions and radiation-induced tissue injury upon exposure to external beam radiotherapy.</p><p><strong>Methods: </strong>For the purpose of this work, we collected blood serum samples from 33 breast cancer patients who received adjuvant radiotherapy. To conduct statistical analysis, we used: (1) linear adjustment to correlate the percent changes of 8-OHdG and 8-NG with the degree of toxicity; and (2) polynomial adaptation and exponential fitting to correlate the percent changes of 8-OHdG and 8-NG with the correlation coefficient <i>r</i> for the development of radiation dermatitis, respectively.</p><p><strong>Results: </strong>According to our findings, there is a statistically significant correlation between the alterations in the 8-OHdG and 8-NG levels and skin grade toxicity across time and varying radiation doses (<i>p</i> < 0.05).</p><p><strong>Conclusions: </strong>Both DNA lesions seem to possess a promising predictive role in radiation dermatitis, while the severity and exact grade of radiation-induced skin toxicity can be determined.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002336"},"PeriodicalIF":0.0,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12464552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145187802","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":"Genetic and epigenetic landscape of O<sup>6</sup>-methylguanine-DNA methyltransferase (MGMT): implications for DNA repair and cancer therapeutics.","authors":"Shishir Singh, Rajeev Nema, Monisha Banerjee, Atar Singh Kushwah","doi":"10.37349/etat.2025.1002335","DOIUrl":"10.37349/etat.2025.1002335","url":null,"abstract":"<p><p>O<sup>6</sup>-Methylguanine-DNA methyltransferase (MGMT) acts as a genomic custodian, reversing alkylation damage to preserve DNA integrity. However, when its regulatory balance tips via promoter methylation, polymorphisms, or epigenetic silencing, MGMT can become a liability, fuelling cancer progression, treatment resistance, and poor outcomes across malignancies. This review uncovers the nuanced control of MGMT, revealing how its genetic and epigenetic shifts shape tumor behavior, therapeutic response, and risk stratification. We aim to transform molecular insights into actionable clinical strategies, reimagining MGMT as both a biomarker and therapeutic lever. We curated high-impact studies (up to 2025) from PubMed, Scopus, and Web of Science, focusing on MGMT modulation, synthetic lethality, CRISPR-based restoration, and epigenetic therapies. Emerging multi-omics and translational frameworks were prioritized. MGMT's activity is choreographed by an intricate interplay of promoter methylation, histone marks, transcriptional regulation, and microRNA influence. These dynamics critically affect sensitivity to alkylating agents like temozolomide. Intriguingly, MGMT also engages with the immune landscape modulating response to immunotherapies. Innovations in multi-omics, single-cell analytics, and AI-based biomarker profiling are unveiling previously hidden regulatory layers. Decoding MGMT's regulation unlocks new therapeutic frontiers. Cutting-edge strategies from CRISPR to liquid biopsy promise more personalized, resistance-proof cancer care.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002335"},"PeriodicalIF":0.0,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12394067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144980971","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}
Yuting Sheng, Daniel M Han, Mark R Wakefield, Yujiang Fang
{"title":"Inflammatory signatures across four photon radiotherapy and proton radiotherapy: mechanisms, mitigation, and quality of life impact.","authors":"Yuting Sheng, Daniel M Han, Mark R Wakefield, Yujiang Fang","doi":"10.37349/etat.2025.1002334","DOIUrl":"10.37349/etat.2025.1002334","url":null,"abstract":"<p><p>Cancer is the second leading cause of death globally and in the United States, second only to cardiovascular disease. Unlike many cardiovascular conditions, cancer is often less preventable, manageable, and curable-even with ongoing technological advancements in medicine. The adverse effects of cancer treatments on cancer patients remain profound due to shared cellular characteristics between cancerous and normal cells; one of the primary adverse effects is treatment-induced inflammation. These inflammatory responses aim to eliminate cancerous cells but often damage normal tissues. Notably, inflammatory side effects vary considerably across the growing diversity of therapeutic approaches. This study reviewed studies between 2007 and 2024, comparing the inflammatory profiles associated with five major radiation therapies (RTs): Three-Dimensional Conformal Radiation Therapy (3D-CRT), Intensity-Modulated Radiation Therapy (IMRT), Image-Guided Radiation Therapy (IGRT), Stereotactic Body Radiation Therapy (SBRT), and Proton Beam Therapy (PBT)-each characterized by distinct mechanistic and therapeutic features. In addition to each radiation modality eliciting distinct inflammatory responses, tissue-specific variability further complicates clinical outcomes. Accordingly, this review also undertakes a cross-tissue comparison of radiation-induced inflammation, with a focus on the gastrointestinal (GI) system, central nervous system (CNS), and skin. However, the variation in treatment modalities and organ-specific inflammatory biomarkers greatly hinders direct comparison across studies. Finally, this review highlights potential inflammatory mitigations, including ambroxol, that may be employed synergistically with RTs, minimizing side effects and enhancing patient outcomes. Taken together, while all modalities offer therapeutic value alongside certain limitations, proton-based therapy demonstrates the greatest potential for minimizing toxicity though its broader adoption remains limited by cost-effectiveness concerns.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002334"},"PeriodicalIF":0.0,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12394066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144981020","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}
Ekaterina S Kuligina, Grigoriy A Yanus, Evgeny N Imyanitov
{"title":"Improvement of the sensitivity of circulating tumor DNA-based liquid biopsy: current approaches and future perspectives.","authors":"Ekaterina S Kuligina, Grigoriy A Yanus, Evgeny N Imyanitov","doi":"10.37349/etat.2025.1002333","DOIUrl":"10.37349/etat.2025.1002333","url":null,"abstract":"<p><p>Liquid biopsy (LB) is a complex of procedures aimed at the detection of tumor-derived fragments (nucleic acids, proteins, cells, etc.) persisting in the blood or other body fluids. It can be utilized for early cancer diagnosis, analysis of biomarkers of tumor drug sensitivity and prognosis, monitoring of minimal residual disease (MRD), etc. Circulating tumor DNA (ctDNA) is an accessible and reliable LB analyte as it may contain tumor-specific mutations and is amenable to efficient detection by next-generation sequencing (NGS) or droplet digital PCR (ddPCR). High level of ctDNA is typically associated with increased tumor burden and poor prognosis, whereas treatment-related ctDNA clearance increases the probability of a favorable disease outcome. Major efforts have been invested in enhancing the analytical performance of ctDNA detection. Stimulation of apoptosis of tumor cells by irradiation of cancer lumps has been shown to result in a transient but modest increase in ctDNA concentration. There are several sophisticated modifications of ultra-deep NGS protocols, which discriminate between \"true\" low-copy mutation-specific signals and sequencing artifacts. Slowing physiological ctDNA decay by interfering with liver macrophages and circulating nucleases has shown promise in animal experiments. Reproducibility of ctDNA-based LB assays remains insufficient for samples with ultra-low content of ctDNA; hence, interlaboratory harmonization of ctDNA testing procedures is of paramount importance.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002333"},"PeriodicalIF":0.0,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12332530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144818392","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}
Rolla Al-Shalabi, Vuanghao Lim, Ibrahim Al-Deeb, Melissa Kilus, Nozlena Abdul Samad
{"title":"Anti-angiogenic effects of <i>Moringa oleifera</i> silver nanoparticles on endothelial cells: in vitro and ex vivo studies.","authors":"Rolla Al-Shalabi, Vuanghao Lim, Ibrahim Al-Deeb, Melissa Kilus, Nozlena Abdul Samad","doi":"10.37349/etat.2025.1002332","DOIUrl":"10.37349/etat.2025.1002332","url":null,"abstract":"<p><strong>Aim: </strong>Angiogenesis, invasion, and tube formation are critical processes in tumor progression and metastasis. The use of nanoparticles derived from natural products presents a promising approach for targeted cancer therapy. This study evaluates the anti-angiogenic and anti-invasive effects of <i>Moringa oleifera</i> silver nanoparticles (MO-AgNPs) as a therapeutic strategy against these processes.</p><p><strong>Methods: </strong>The anti-angiogenic and anti-invasive activities of MO-AgNPs were investigated using a series of in vitro and ex vivo models. These included the rat aortic ring assay, endothelial tube formation assay, cell invasion assay using endothelial cell lines (Ea.hy926), and a three-dimensional (3D) co-culture spheroid model to simulate tumor microenvironment behavior. Comparisons were made with known inhibitors: quercetin (15.11 μg/mL) and suramin (100 μg/mL).</p><p><strong>Results: </strong>MO-AgNPs at 12 μg/mL significantly inhibited Ea.hy926 cell invasion by 62.10% and significantly suppressed endothelial tube formation, comparable to the effect of quercetin. In the ex vivo aortic ring assay, MO-AgNPs reduced microvessel sprouting by 83.824 ± 0.081%, surpassing the inhibition achieved by suramin. Additionally, in the 3D spheroid model, MO-AgNPs at concentrations of 12 μg/mL and 6 μg/mL, as well as quercetin, significantly reduced spheroid diameter by day 14, indicating suppressed invasive potential and angiogenic support.</p><p><strong>Conclusions: </strong>MO-AgNPs exhibit strong anti-angiogenic and anti-invasive effects across various tumor-relevant models, highlighting their potential as a therapeutic agent against tumor progression and angiogenesis-related diseases. These results support further investigation of MO-AgNPs as a novel nanotherapeutic for cancer treatment.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002332"},"PeriodicalIF":0.0,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12314757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144777059","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}
Federica Martorana, Sabrina Nucera, Gianmarco Motta, Maria Vita Sanò, Carlo Carnaghi, Marialuisa Puglisi, Claudia Gelsomino, Giuseppe Corsaro, Chiara Conti, Lucia Motta, Giuliana Pavone, Stefano Marletta, Giada Maria Vecchio, Gaetano Magro, Giuseppe Catanuto, Gaetano Castiglione, Francesco Caruso, Antonio Rizzo, Michele Caruso, Paolo Vigneri
{"title":"Correlation between histopathological features and recurrence score according to menopausal status in HR+/HER2- breast cancer patients: a retrospective study.","authors":"Federica Martorana, Sabrina Nucera, Gianmarco Motta, Maria Vita Sanò, Carlo Carnaghi, Marialuisa Puglisi, Claudia Gelsomino, Giuseppe Corsaro, Chiara Conti, Lucia Motta, Giuliana Pavone, Stefano Marletta, Giada Maria Vecchio, Gaetano Magro, Giuseppe Catanuto, Gaetano Castiglione, Francesco Caruso, Antonio Rizzo, Michele Caruso, Paolo Vigneri","doi":"10.37349/etat.2025.1002331","DOIUrl":"10.37349/etat.2025.1002331","url":null,"abstract":"<p><strong>Aim: </strong>Clinico-pathological features have traditionally guided prognosis and adjuvant therapy for breast cancer (BC) patients. In the past decade, genomic tests such as Oncotype DX entered clinical practice to refine risk stratification and predict chemotherapy benefit for hormone-receptor positive (HR+)/human epidermal growth factor-receptor 2 negative (HER2-) BC patients after surgery. This is a retrospective analysis to investigate the correlation between histopathological parameters and recurrence score (RS), accounting for menopausal status.</p><p><strong>Methods: </strong>Data on HR+/HER2- early BC patients who underwent Oncotype DX were collected using an institutional database. Clinico-pathological characteristics were retrieved. Linear regression was used with RS as a continuous outcome, while logistic regression was performed for pre- and post-menopausal patients, dichotomizing RS at thresholds of 16 and 25, respectively.</p><p><strong>Results: </strong>A total of 180 women were included (35% pre-menopausal, 65% post-menopausal). Median age was 57.5 years. Most patients had pT1, pN0, G2 BC, with median estrogen receptor (ER) expression of 95% and a median Ki67 of 25%. Median RS was 16 [interquartile range (IQR) 12-22] in the overall cohort, 15 in pre-menopausal, and 17 in post-menopausal women. In the entire cohort, RS significantly correlated with G3 (<i>P</i> = 0.01), Ki67% (<i>P</i> < 0.0001), ER% (<i>P</i> = 0.03), and progesterone receptor (PgR)% (<i>P</i> < 0.0001). In pre-menopausal patients, only Ki67% (<i>P</i> = 0.02), ER% (<i>P</i> = 0.01), and PgR% (<i>P</i> < 0.0001) showed significant correlations, while in post-menopausal patients, G3 (<i>P</i> = 0.03), Ki67% (<i>P</i> = 0.001), and PgR% (<i>P</i> < 0.0001) achieved statistical significance. Logistic regression analysis showed that in pre-menopausal patients, PgR% predicted RS > 16 [odds ratio (OR) 0.95, <i>P</i> = 0.001]. In post-menopausal women, Ki67% (OR 1.08, <i>P</i> = 0.031) and PgR% (OR 0.95, <i>P</i> < 0.0001) predicted RS > 25.</p><p><strong>Conclusions: </strong>In this patient cohort, classical clinico-pathological features showed varying correlations with RS, depending on menopausal status. These findings highlight the complexity of risk stratification, suggesting that further research is needed to better understand the factors influencing RS and its clinical utility.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002331"},"PeriodicalIF":0.0,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12290898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144735836","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}
Elena V Preobrazhenskaya, Rimma S Mulkidjan, Fyodor A Zagrebin, Alexandr A Romanko, Evgeniya S Saitova, Polina R Korzun, Jeyla O Binnatova, Vladislav I Tiurin, Ilya V Bizin, Evgeny N Imyanitov
{"title":"Novel kinase-activating genetic events in non-small cell lung carcinomas.","authors":"Elena V Preobrazhenskaya, Rimma S Mulkidjan, Fyodor A Zagrebin, Alexandr A Romanko, Evgeniya S Saitova, Polina R Korzun, Jeyla O Binnatova, Vladislav I Tiurin, Ilya V Bizin, Evgeny N Imyanitov","doi":"10.37349/etat.2025.1002330","DOIUrl":"10.37349/etat.2025.1002330","url":null,"abstract":"<p><strong>Aim: </strong>This study aimed at the identification of new druggable alterations in non-small cell lung carcinomas (NSCLCs).</p><p><strong>Methods: </strong>RNA next generation sequencing (NGS) analysis for 650 protein kinase genes was performed for 89 NSCLCs obtained from young-onset and/or female non-smokers, who were negative for activating events involving <i>EGFR</i>, <i>ALK</i>, <i>ROS1</i>, <i>RET</i>, <i>MET</i>, <i>NTRK1/2/3</i>, <i>BRAF</i>, <i>HER2</i>, <i>KRAS</i>, or <i>NRAS</i> genes.</p><p><strong>Results: </strong>RNA sequencing identified 32 in-frame rearrangements, including 9 instances of fully preserved and 8 tumors with partially preserved tyrosine kinase domains. These 17 translocations were further analyzed in 1,059 mutation-negative NSCLCs, which resulted in the identification of two additional tumors with <i>ADK</i>::<i>KAT6B</i> rearrangement and one carcinoma carrying <i>RPS6KB1</i>::<i>VMP1</i> fusion. The recently reported <i>CLIP1</i>::<i>LTK</i> gene fusion was tested in 2,754 NSCLCs, which were negative for all known actionable mutations, however, no new instances of this translocation have been observed. We further analyzed RNA sequencing results of 89 NSCLCs for mutations affecting the kinase domain of the involved gene. There were 53 substitutions with a combined annotation dependent depletion (CADD) score above 25; all these lesions turned out to be unique, as the analysis of 551 additional NSCLCs revealed no recurrent alterations. <i>ROS1</i>, <i>LTK</i>, and <i>FGFR4</i> high-level overexpression was observed in 1 out of 89 tumors each.</p><p><strong>Conclusions: </strong>This study demonstrates the scarcity of yet unknown kinase-activating alterations in NSCLCs.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002330"},"PeriodicalIF":0.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12256180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144638843","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}
Gurkaranjot Singh, Zuhair Chaudhry, Anik Boyadzhyan, Kayvan Sasaninia, Vikrant Rai
{"title":"Dysbiosis and colorectal cancer: conducive factors, biological and molecular role, and therapeutic prospectives.","authors":"Gurkaranjot Singh, Zuhair Chaudhry, Anik Boyadzhyan, Kayvan Sasaninia, Vikrant Rai","doi":"10.37349/etat.2025.1002329","DOIUrl":"10.37349/etat.2025.1002329","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is the third leading cause of cancer-related death in the United States. Emerging evidence highlights the significant role of gut microbiota dysbiosis, characterized by a reduction in beneficial bacteria and an increase in pro-inflammatory and pro-carcinogenic bacteria, in CRC pathogenesis. Both genetic and environmental factors, including diet, antibiotic use, physical activity, aging, and obesity, contribute to this microbial imbalance. Dysbiosis promotes chronic inflammation and immune dysregulation, which facilitates tumor initiation and progression. This review examines the intricate interactions between gut microbiota, immune modulation, and CRC development. It explores current and emerging therapeutic strategies that target the microbiome to enhance treatment efficacy, discusses interventions aimed at restoring healthy microbiota in CRC patients, and outlines future directions for microbiome-based therapies to improve clinical outcomes.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002329"},"PeriodicalIF":0.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144531396","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}