{"title":"Multi-Omics Analysis Revealed That TAOK1 Can Be Used as a Prognostic Marker and Target in a Variety of Tumors, Especially in Cervical Cancer.","authors":"Li Ning, Xiu Li, Yating Xu, Yu Si, Hongting Zhao, Qingling Ren","doi":"10.2147/OTT.S506582","DOIUrl":"10.2147/OTT.S506582","url":null,"abstract":"<p><strong>Background: </strong>Thousand and One Kinase 1 (TAOK1), a member of the MAPK kinase family, plays a crucial role in processes like microtubule dynamics, DNA damage response, and neurodevelopment. While TAOK1 is linked to tumorigenesis, its oncogenic role across cancers remains unclear. This study aims to explore the relationship between TAOK1 expression, prognosis, and immune function in various cancers.</p><p><strong>Methods: </strong>We analyzed TAOK1 expression in multiple cancers using TCGA, GEO, CCLE, and other bioinformatics databases. The correlation between TAOK1 expression and immune cell infiltration was assessed with the ESTIMATE algorithm. We also examined associations with tumor stemness, DNA methylation, gene copy number alterations, and drug sensitivity. The oncogenic role of TAOK1 was further evaluated in vitro with SiHa and A2780 cells and in vivo with TAOK1 overexpression in SiHa cells.</p><p><strong>Results: </strong>TAOK1 is a key prognostic biomarker in various cancers and its high expression is associated with poor prognosis. It showed a significant negative correlation with immune cell infiltration and immune checkpoints. GSEA identified its involvement in key tumour pathways, highlighting the therapeutic potential of inhibiting the TAOK1 gene. The high expression of TAOK1 is associated with DNA methylation and gene copy number variation, and in addition its upstream regulator, EP300, is closely associated with TAOK1 expression. In vitro cellular experiments demonstrated that inhibition of TAOK1 reduced the proliferation of SiHa and A2780 cells, whereas overexpression of TAOK1 in SiHa cells promoted growth. These findings were further validated in vivo by nude mouse tumourigenicity assay and human tissue immunohistochemistry.</p><p><strong>Conclusion: </strong>TAOK1 serves as a promising prognostic biomarker and potential therapeutic target, especially for cervical cancer. These results support its clinical potential in cancer prognosis and treatment strategies.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"335-353"},"PeriodicalIF":2.7,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11920640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OncoTargets and therapyPub Date : 2025-03-14eCollection Date: 2025-01-01DOI: 10.2147/OTT.S486400
Rafael Cerón Maldonado, Adolfo Martínez Tovar, Christian Omar Ramos Peñafiel, Adrián De la Cruz Rosas, Anel Irais García Laguna, Iveth Mendoza Salas, Carlos Martínez Murillo, Gilberto Israel Barranco Lampón, Efreen Horacio Montaño Figueroa, Silvia Jiménez-Morales, Irma Olarte Carrillo
{"title":"<i>CYP3A5</i> Polymorphism in Circulating Tumor Cells Confers an Increased Disease-Free Survival in DLBCL Patients Treated with R-CHOP.","authors":"Rafael Cerón Maldonado, Adolfo Martínez Tovar, Christian Omar Ramos Peñafiel, Adrián De la Cruz Rosas, Anel Irais García Laguna, Iveth Mendoza Salas, Carlos Martínez Murillo, Gilberto Israel Barranco Lampón, Efreen Horacio Montaño Figueroa, Silvia Jiménez-Morales, Irma Olarte Carrillo","doi":"10.2147/OTT.S486400","DOIUrl":"10.2147/OTT.S486400","url":null,"abstract":"<p><strong>Purpose: </strong>Diffuse Large B-Cell Lymphoma (DLBCL) is a heterogeneous aggressive lymphoid neoplasm. Cases of refractoriness and relapse persist in approximately 40% of patients treated with first-line R-CHOP regimen, thus, the identification of factors associated with disease progression have become a necessity. Diverse polymorphisms in genes encoding proteins involved in the metabolism and elimination of chemotherapeutic drugs have been studied as potential causes of treatment failure. In oncology, liquid biopsies have emerged as a non-invasive method for detecting circulating biomarkers, thereby strengthening both diagnosis and prognosis for patients. Therefore, the purpose of this study was to determine polymorphisms in Circulating Tumor Cells (CTCs) to describe the relevance of liquid biopsy in the clinical outcomes of patients with DLBCL.</p><p><strong>Patients and methods: </strong>We analyzed 102 liquid biopsies of peripheral blood from DLBCL patients, of which CTCs were isolated by density gradient and CD20 immunomagnetic antibodies. Allelic discrimination assays were performed to analyze <i>ABCB1 C3435T, ABCG2 C421A</i> and <i>CYP3A5 A6986G</i> polymorphisms. Overall survival (OS) and disease-free survival (DFS) analysis were performed using Kaplan-Meier curves and risk analysis was performed using Cox regression.</p><p><strong>Results: </strong>We found that GG genotype of <i>CYP3A5 A6986G</i> was associated with a longer DFS (68.6% vs 49%, p=0.019) and lower risk of course with adverse event related to disease (progression, relapse and death) (OR 0.374, CI 0.187-0.745, p=0.011). No significant associations were found between <i>ABCB1 C3435T</i> and <i>ABCG2 C421A</i> genotype with the clinical outcome.</p><p><strong>Conclusion: </strong>In this study, we demonstrated that in CTCs derived from liquid biopsies, the GG genotype in the <i>CYP3A5 A6986G</i>, which is related to the metabolism and elimination of chemotherapy drugs, impacts in longer DFS. These findings confirm the relevance of circulating biomarkers in non-invasive biological samples for strengthening the prognosis of DLBCL.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"355-366"},"PeriodicalIF":2.7,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11920637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OncoTargets and therapyPub Date : 2025-03-10eCollection Date: 2025-01-01DOI: 10.2147/OTT.S504279
JiaQi Liu, Jun Chu
{"title":"Comprehensive Treatment of Anaplastic Thyroid Cancer: A Case Report.","authors":"JiaQi Liu, Jun Chu","doi":"10.2147/OTT.S504279","DOIUrl":"https://doi.org/10.2147/OTT.S504279","url":null,"abstract":"<p><strong>Background: </strong>Anaplastic thyroid cancer (ATC) is a rare, highly aggressive malignancy that accounts for less than 2% of thyroid cancers but contributes significantly to morbidity and mortality. Despite its rapid progression and poor prognosis, recent advances in targeted therapies and immunotherapies offer some hope for treatment.</p><p><strong>Case presentation: </strong>A 55-year-old female with no prior thyroid disease was diagnosed with advanced ATC after a routine check-up revealed a neck mass. She presented with a tumor compressing the trachea, recurrent laryngeal nerve, and carotid sinus, accompanied by Horner's syndrome. Fine-needle aspiration confirmed anaplastic sarcoma. After a multidisciplinary consultation, the patient was treated with anlotinib, tislelizumab, and albumin-bound paclitaxel, resulting in significant tumor shrinkage and symptomatic relief. However, due to financial constraints, treatment was discontinued. One month later, the tumor rapidly progressed, leading to tracheal compression and asphyxiation, causing her death.</p><p><strong>Conclusion: </strong>This case highlights the potential benefits of combination therapy for advanced ATC, demonstrating significant temporary improvements. However, the discontinuation of treatment due to financial limitations led to rapid disease progression, underscoring the importance of continuous, accessible care. This case also emphasizes the impact of socio-economic factors on patient outcomes and survival in aggressive cancers.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"325-333"},"PeriodicalIF":2.7,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11908399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OncoTargets and therapyPub Date : 2025-03-06eCollection Date: 2025-01-01DOI: 10.2147/OTT.S484293
Meng Cao, Rong Wang, Xiaohan Cheng, Huiping Yu, Qi Tong, Yongzhong Yao
{"title":"Patient-Derived Organoids for Guiding Neoadjuvant Chemotherapy in Bilateral Primary Breast Cancer: A Case Report.","authors":"Meng Cao, Rong Wang, Xiaohan Cheng, Huiping Yu, Qi Tong, Yongzhong Yao","doi":"10.2147/OTT.S484293","DOIUrl":"10.2147/OTT.S484293","url":null,"abstract":"<p><p>Neoadjuvant chemotherapy (NAC) is the standard of care for locally advanced breast cancer, but the response to chemotherapy is unpredictable due to unknown information on the tumor drug sensitivity. Patient-derived organoids (PDOs) have recently been revealed to be a promising platform for assessing drug sensitivity in many cancers. A 46-year-old woman presented to the hospital due to an accidentally discovered mass in the left breast. Based on core-needle biopsies, pathologic examination showed invasive breast cancer in both breasts. In combination with immunohistochemistry, the patient was diagnosed with left breast cancer IIB with axillary lymphatic metastasis and right breast cancer IIA. The NAC with albumin-bound paclitaxel, epirubicin and cyclophosphamide was used. Although partial response was assessed overall, the left tumor did not lessen significantly; thus, organoids from bilateral breasts were cultured. After treatment with PDO-sensitive vinorelbine and carboplatin, partial response was achieved in the left compared with the initial tumor. Meanwhile, bilateral mastectomy was performed successfully, with pathological complete response achieved in the right. This typical case suggests that the PDOs from bilateral primary breast cancers can serve as a powerful tool to identify the sensitivity to NAC, thus providing novel treatment options at the patient-specific level.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"319-324"},"PeriodicalIF":2.7,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OncoTargets and therapyPub Date : 2025-03-02eCollection Date: 2025-01-01DOI: 10.2147/OTT.S499226
Marta Muzzana, Massimo Broggini, Giovanna Damia
{"title":"The Landscape of PARP Inhibitors in Solid Cancers.","authors":"Marta Muzzana, Massimo Broggini, Giovanna Damia","doi":"10.2147/OTT.S499226","DOIUrl":"10.2147/OTT.S499226","url":null,"abstract":"<p><p>PARP inhibitors are a class of agents that have shown significant preclinical activity in models defective in homologous recombination (HR). The identification of synthetic lethality between HR defects and PARP inhibition led to several clinical trials in tumors with known HR defects (initially mutations in <i>BRCA1/2</i> genes and subsequently in other genes involved in HR). These studies demonstrated significant responses in breast and ovarian cancers, which are known to have a significant proportion of patients with HR defects. Since the approval of the first PARP inhibitor (PARPi), olaparib, several other inhibitors have been developed, expanding the armamentarium available to clinicians in this setting. The positive results obtained in breast and ovarian cancer have expanded the use of PARPi in other solid tumors with HR defects, including prostate and pancreatic cancer in which these defects have been identified. The clinical trials have demonstrated responses to PARPi which are now also available for the subset of patients with prostate and pancreatic cancer with HR defects. This review summarizes the results obtained in solid tumors with PARPi and their potential use when combined with other agents, including immune checkpoint inhibitors that are likely to further increase the survival of these patients which still needs a dramatic improvement.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"297-317"},"PeriodicalIF":2.7,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Efficacy and Safety of Combined PD-1 Inhibitor With Induction Chemotherapy Followed by IMRT Plus Nimotuzumab in Locally Advanced Nasopharyngeal Carcinoma: A Retrospective Analysis.","authors":"Kebin Chen, Xiaopeng Huang, Jiawei Chen, Shuai Zhang","doi":"10.2147/OTT.S503674","DOIUrl":"10.2147/OTT.S503674","url":null,"abstract":"<p><strong>Background: </strong>Induction chemotherapy (IC) is the standard treatment protocol for locally advanced nasopharyngeal carcinoma (LANPC), though concerns persist regarding high rates of recurrence and metastasis. This retrospective study aims to evaluate the efficacy, potential benefits, and safety of combining PD-1 inhibitors with IC, followed by nimotuzumab and intensity-modulated radiation therapy (IMRT).</p><p><strong>Methodology: </strong>We analyzed data from 103 patients diagnosed with non-keratinizing LANPC (according to WHO criteria) at clinical stages III-IVA. These patients, treated from May 2020 to November 2023, received four cycles of IC combined with PD-1 inhibitors, followed by nimotuzumab and IMRT. Efficacy assessments were conducted according to RECIST v1.1 guidelines, with the primary endpoint being a clinical complete response (CCR), defined as the absence of detectable tumors or mucosal bulges upon nasoendoscopy.</p><p><strong>Results: </strong>Among the evaluable patients, the CCR rate reached 66% (95% CI, 56-75%), while the objective response rate (ORR) was 97% (95% CI, 92-99%) and the disease control rate (DCR) reached 99% (95% CI, 95-100%). During the median follow-up of 16.1 months, neither the median progression-free survival (PFS) nor median overall survival (OS) was reached. Notably, patients with T4-stage disease exhibited lower CCR rates, highlighting stage-specific variations in treatment responses. The treatment regimen was well-tolerated, with no significant adverse safety events reported.</p><p><strong>Conclusion: </strong>The combination of PD-1 inhibitors with IC, followed by nimotuzumab and IMRT, shows promising efficacy and safety in the treatment of LANPC.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"283-296"},"PeriodicalIF":2.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11867642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OncoTargets and therapyPub Date : 2025-02-20eCollection Date: 2025-01-01DOI: 10.2147/OTT.S505376
Reham M Alahmadi, Maaweya Awadalla, Najat Marraiki, Mohammed Alswayyed, Hajar A Alshehri, Amjad Alsahli, Hatim A Khoja, Osamah T Khojah, Rawan M Alahmadi, Nada Farid, Bandar Alosaimi
{"title":"Profiling the Tumor Immune Microenvironment of HPV-Associated Base of Tongue Squamous Cell Carcinoma.","authors":"Reham M Alahmadi, Maaweya Awadalla, Najat Marraiki, Mohammed Alswayyed, Hajar A Alshehri, Amjad Alsahli, Hatim A Khoja, Osamah T Khojah, Rawan M Alahmadi, Nada Farid, Bandar Alosaimi","doi":"10.2147/OTT.S505376","DOIUrl":"10.2147/OTT.S505376","url":null,"abstract":"<p><strong>Background: </strong>Base of tongue squamous cell carcinoma (BOTSCC) is a prevalent and aggressive form of oral cancer, often associated with poor patient outcomes. The tumor microenvironment (TME) of HPV-positive BOTSCC is critical in influencing cancer progression and treatment response.</p><p><strong>Objective: </strong>This study aims to analyze the TME of HPV-positive BOTSCC by examining the expression of key genes involved in various biological processes.</p><p><strong>Methods: </strong>We utilized the RT2 Profiler PCR Array to quantify the expression of 168 genes related to inflammation, immunity, oncogenesis, tumor suppression, apoptosis, and angiogenesis. Enrichment analysis of cancer hallmarks was performed on all upregulated genes. Additionally, we investigated the correlation between the expression levels of the ten most highly upregulated genes and survival prognosis in HPV-associated BOTSCC patients.</p><p><strong>Results: </strong>Our analysis revealed dysregulation of 42 genes associated with tumor-immune interactions, with 20 genes upregulated and 22 downregulated. Furthermore, we identified 64 genes linked to cancer development, with 33 upregulated and 31 downregulated. High-risk HPV (hr-HPV) genotypes were found in 81% of patients, predominantly HPV-35 and HPV-16.</p><p><strong>Conclusion: </strong>This study highlights the complexity of the HPV-positive BOTSCC TME, underscoring the need for further research into molecular pathways and immune interactions to identify new therapeutic targets for improved cancer treatment.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"263-281"},"PeriodicalIF":2.7,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11849419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OncoTargets and therapyPub Date : 2025-02-18eCollection Date: 2025-01-01DOI: 10.2147/OTT.S493643
Khansa Ali Sheikh, Momna Amjad, Mahnoor Tabassum Irfan, Sumaira Anjum, Tanveer Majeed, Muhammad Usman Riaz, Amar Yasser Jassim, Elham Abdullatif M Sharif, Wisam Nabeel Ibrahim
{"title":"Exploring TGF-β Signaling in Cancer Progression: Prospects and Therapeutic Strategies.","authors":"Khansa Ali Sheikh, Momna Amjad, Mahnoor Tabassum Irfan, Sumaira Anjum, Tanveer Majeed, Muhammad Usman Riaz, Amar Yasser Jassim, Elham Abdullatif M Sharif, Wisam Nabeel Ibrahim","doi":"10.2147/OTT.S493643","DOIUrl":"10.2147/OTT.S493643","url":null,"abstract":"<p><p>Cancer persists as a ubiquitous global challenge despite the remarkable advances. It is caused by uncontrolled cell growth and metastasis. The Transforming Growth Factor-beta (TGF-β) signaling pathway is considered a primary regulator of various normal physiological processes in the human body. Recently, factors determining the nature of TGF-β response have received attention, specifically its signaling pathway which can be an attractive therapeutic target for various cancer treatments. The TGF-β receptor is activated by its ligands and undergoes transduction of signals via canonical (SMAD dependent) or non-canonical (SMAD independent) signaling pathways regulating several cellular functions. Furthermore, the cross talk of the TGF-β signaling pathway cross with other signaling pathways has shown the controlled regulation of cellular functions. This review highlights the cross talk between various major signaling pathways and TGF-β. These signaling pathways include Wnt, NF-κB, PI3K/Akt, and Hedgehog (Hh). TGF-β signaling pathway has a dual role at different stages. It can suppress tumor formation at early stages and promote progression at advanced stages. This complex behaviour of TGF-β has made it a promising target for therapeutic interventions. Moreover, many strategies have been designed to control TGF-β signaling pathways at different levels, inhibiting tumor-promoting while enhancing tumor-suppressive effects, each with unique molecular mechanisms and clinical implications. This review also discusses various therapeutic inhibitors including ligand traps, small molecule inhibitors (SMIs), monoclonal antibodies (mAbs), and antisense oligonucleotides which target specific components of TGF-β signaling pathway to inhibit TGF-β signaling and are studied in both preclinical and clinical trials for different types of cancer. The review also highlights the prospect of TGF-β signaling in normal physiology and in the case of dysregulation, TGF-β inhibitors, and different therapeutic effects in cancer therapy along with the perspective of combinational therapies to treat cancer.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"233-262"},"PeriodicalIF":2.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OncoTargets and therapyPub Date : 2025-02-12eCollection Date: 2025-01-01DOI: 10.2147/OTT.S505074
Huiye Yang, Jie Zhu, Xiaotao Wang
{"title":"Comprehensive Analysis Identifies Hsa_circ_0058191 as a Potential Drug Resistance Target in Multiple Myeloma.","authors":"Huiye Yang, Jie Zhu, Xiaotao Wang","doi":"10.2147/OTT.S505074","DOIUrl":"10.2147/OTT.S505074","url":null,"abstract":"<p><strong>Background: </strong>Multiple Myeloma (MM) is the second most common hematologic malignancy, which exhibits strong resistance to bortezomib, the first-line treatment. Circular RNAs (circRNAs) are increasingly considered as important drivers of drug resistance across various cancers, but their roles in multiple myeloma are not well understood.</p><p><strong>Aim: </strong>To investigate and identify potential circRNA targets and their roles in the mechanisms of bortezomib resistance.</p><p><strong>Methods: </strong>Bortezomib-resistant MM patient-specific circRNAs were screened using Arraystar circRNA microarrays. The MM circRNA dataset from the GEO database was analyzed with GEO2R to identify candidate circRNAs associated with MM progression and drug resistance. CircRNA-forming and loop-forming sites, along with their structures, were identified via Sanger sequencing. The identified circRNA was validated by qRT-PCR in MM patients with and without bortezomib resistance. Bioinformatic analysis through CircInteractome was conducted to predict potential miRNA and RBP binding for the core circRNAs. Metascape was employed to perform RBP pathway analysis to identify specific biological processes in circRNAs.</p><p><strong>Results: </strong>The hsa_circ_0058191 was found to be overexpressed in bortezomib-resistant MM patient samples, suggesting its pivotal role in drug resistance mechanisms. The interaction of hsa_circ_0058191 with miR-660 and AGO2 as determined through bioinformatic predictions, indicated that it regulates RNA modification and mRNA regulation pathways. These molecular interactions expand our understanding of the mechanisms of drug resistance in multiple myeloma.</p><p><strong>Conclusion: </strong>This study identified the role of hsa_circ_0058191 in the development of drug resistance in MM, which provides a theoretical foundation for designing potential therapeutic strategies to prevent drug resistance.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"225-231"},"PeriodicalIF":2.7,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11831480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Comprehensive Review of Advances in Molecular Mechanisms and Targeted Therapies for the Specific Type of Cystic Lung Cancer.","authors":"Beinuo Wang, Cheng Shen, Danlu Liu, Zhenghao Dong, Xiang Lin, Hu Liao","doi":"10.2147/OTT.S495018","DOIUrl":"https://doi.org/10.2147/OTT.S495018","url":null,"abstract":"<p><strong>Background and objective: </strong>Cystic lung cancer (CLC) presents diagnostic and treatment challenges due to its complex imaging features and unclear molecular mechanisms. Although surgery and standard chemotherapy are frequently used, there is limited information on targeted therapy and other precision treatments. It is crucial to comprehensively understand the molecular mechanisms and explore precision treatments based on targeted therapy.</p><p><strong>Methods: </strong>Topic keywords including \"CLC\", \"cystic lung cancer\", \"cavitary lung cancer\", \"Lung cancer associated with cystic airspaces\", and \"lung cancer\" with (\"sac cavity\" OR \"cystic degeneration\" OR \"thin-walled cavity\" OR \"adenocystic carcinoma\" OR \"cystic airspaces\" OR \"pulmonary cysts\" OR \"adenoid cystic carcinoma\") searched in the relevant databases, such as PubMed, Google Scholar, and CNKI (China National Knowledge Infrastructure). Then, we reviewed and analyzed the molecular mechanism and its precision therapeutics of CLC.</p><p><strong>Key content and findings: </strong>Various subtypes of CLC can be identified through histopathological examination, such as cystic adenocarcinoma, and squamous cell carcinoma. However, we still have much to learn about the molecular mechanisms behind CLC. Gene mutation, the abnormal tumor microenvironment, and immune dysfunction are the main mechanisms, along with potential factors like epigenetic modifications and gene susceptibility related to COPD. Recent advancements in treatment include targeted therapies, such as targeted inhibitors for EGFR, ALK, ROS1, BRAF, and MET. Surgical treatment, standardized chemotherapy, immunotherapy, and combination therapy remain important. Future research should focus on genomic and molecular profiling, and the development of precision medicine based on insights into the heterogeneity of CLC. Additionally, investigating resistance mechanisms and developing predictive biomarkers are important for future CLC research.</p><p><strong>Conclusion: </strong>The key molecular mechanisms of CLC involve gene mutations and TME immune dysfunction. CLC still requires standard comprehensive treatment based on lung cancer staging, and targeted therapy has shown significant advantages and development prospects.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"211-224"},"PeriodicalIF":2.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}