Current Problems in Cancer最新文献

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IF 2.5 4区医学 Q3 ONCOLOGY

Current Problems in Cancer

Pub Date : 2025-02-01 DOI: 10.1016/S0147-0272(25)00003-0

引用次数: 0

Ophthalmologic toxicities of antineoplastic agents in genitourinary cancers: Mechanisms, management, and clinical implications 泌尿生殖系统肿瘤中抗肿瘤药物的眼科毒性：机制、管理和临床意义。

IF 2.5 4区医学 Q3 ONCOLOGY

Current Problems in Cancer

Pub Date : 2025-02-01 DOI: 10.1016/j.currproblcancer.2024.101171

Aditya Mahadevan , Omid Yazdanpanah , Vivek Patel , David J. Benjamin , Arash Rezazadeh Kalebasty

Genitourinary cancers affect over 480,000 patients in the United States annually. While promising therapeutic modalities continue to emerge, notably immune checkpoint inhibitors, molecular targeted therapies, antibody-drug conjugates, and radioligand therapies, these treatments are associated with a spectrum of adverse side-effects, including ophthalmologic toxicities. In this review, we cover the most commonly used antineoplastic agents for the kidneys, bladder, urinary tracts, prostate, testis, and penis, detailing mechanism, indication, and recent trials supporting their use. For each category of antineoplastic therapy, we describe the epidemiology, management, and clinical presentation, of common ophthalmologic toxicities stemming from these agents. This review serves to augment awareness and recognition of possible ophthalmologic manifestations resulting from the use of antineoplastic agents in genitourinary malignancy. Early identification of these side effects can hasten ophthalmology referral and ultimately improve visual outcomes in patients experiencing medication-induced ocular toxicities.

在美国，泌尿生殖系统癌症每年影响超过48万患者。虽然有希望的治疗方式不断出现，特别是免疫检查点抑制剂，分子靶向治疗，抗体-药物偶联物和放射配体治疗，但这些治疗方法具有一系列不良副作用，包括眼科毒性。在这篇综述中，我们涵盖了最常用的用于肾脏、膀胱、尿路、前列腺、睾丸和阴茎的抗肿瘤药物，详细介绍了其机制、适应症和支持其使用的最新试验。对于每一类抗肿瘤治疗，我们描述了流行病学，管理和临床表现，常见的眼科毒性源于这些药物。本综述旨在提高对泌尿生殖系统恶性肿瘤中使用抗肿瘤药物可能引起的眼科表现的认识和认识。早期识别这些副作用可以加快眼科转诊，并最终改善经历药物性眼毒性的患者的视力结果。

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引用次数: 0

Comparison of efficacy and toxicity of chemotherapeutic regimens used as adjuvant and/or neoadjuvant chemotherapy in penile cancer patients 辅助和/或新辅助化疗方案在阴茎癌患者中的疗效和毒性比较。

IF 2.5 4区医学 Q3 ONCOLOGY

Current Problems in Cancer

Pub Date : 2025-02-01 DOI: 10.1016/j.currproblcancer.2025.101185

Usman Dhasthakeer , Ambika Nand Jha , Ashok Kumar Gupta

Objective

To compare the efficacy and toxicity of different chemotherapeutic regimens used as adjuvant or neoadjuvant chemotherapy in penile cancer patients.

Methodology

This observational study was carried out at Mahavir Cancer Sansthan & Research Centre (MCSRC), Patna, involving 112 patients who received various chemotherapy regimens: 5-Fluorouracil with Cisplatin (FP), Paclitaxel with Carboplatin (TP₁), Paclitaxel with Cisplatin (TP₂), and Paclitaxel with Ifosfamide and Cisplatin (TIP). Efficacy was assessed based on tumor response after Neoadjuvant Chemotherapy (NACT) using RECIST v1.1, and Disease-Free Survival (DFS) was calculated with the Kaplan-Meier method. Chemotherapy toxicity was evaluated using CTCAE v4.03, and statistical analysis was performed with SPSS v22.

Results

The mean age of the penile cancer patients was found to be 53.5 years. The most of the patients comes under stage-IIIb (62 patients – 55.4%). Out of 88 FP received patients, 28 were treated with NACT in which 24 had partial response (PR) and 4 had progressive disease (PD). The objective response rate (ORR) for this group was found to be 85.71%. Out of 21 TP₁ received patients, 9 were treated with NACT in which 6 had CR and 3 had PR, therefore ORR was found to be 100%. Only one Patient received TIP as NACT had PR. The median DFS rate was found to be 6 months for ACT and 7 months for NACT in FP chemotherapy, whereas 10 months was found to be for ACT and NACT of TP₁ combinations. The patients received TP₁ combinations, had more than 6 months of DFS rate. The grade I-III haematological toxicity of anaemia, lymphocytopenia and thrombocytopenia was observed more in FP than TP₁ and TP₂ combinations. The grade I-III non-haematological toxicity was showed for all chemotherapy combinations.

Conclusion

Overall, the TP₁ regimen stands out as the most effective and well-tolerated chemotherapy regimen for penile cancer, demonstrating both superior survival outcomes and a more favourable toxicity profile compared to the FP regimen.

目的：比较不同化疗方案作为辅助或新辅助化疗在阴茎癌患者中的疗效和毒性。方法：本观察性研究在巴特那Mahavir Cancer Sansthan & Research Centre （MCSRC）进行，纳入112例接受不同化疗方案的患者：5-氟尿嘧啶+顺铂（FP）、紫杉醇+卡铂（TP1）、紫杉醇+顺铂（TP2）、紫杉醇+异环磷酰胺+顺铂（TIP）。采用RECIST v1.1基于新辅助化疗（NACT）后肿瘤反应评估疗效，采用Kaplan-Meier法计算无病生存期（DFS）。化疗毒性评价采用CTCAE v4.03软件，统计学分析采用SPSS v22软件。结果：阴茎癌患者的平均年龄为53.5岁。大多数患者处于iiib期（62例- 55.4%）。在接受FP治疗的88例患者中，28例接受NACT治疗，其中24例部分缓解（PR）， 4例进展性疾病（PD）。本组患者客观有效率（ORR）为85.71%。21例TP1患者中，9例接受NACT治疗，其中6例发生CR， 3例发生PR，因此ORR为100%。在FP化疗中，ACT和NACT的中位DFS分别为6个月和7个月，而TP1联合使用ACT和NACT的中位DFS为10个月。采用TP1联合治疗的患者，DFS均大于6个月。与TP1和TP2联合用药相比，FP组贫血、淋巴细胞减少和血小板减少的I-III级血液学毒性更高。所有化疗组合均显示I-III级非血液学毒性。结论：总的来说，TP1方案是治疗阴茎癌最有效和耐受性良好的化疗方案，与FP方案相比，TP1方案显示出更好的生存结果和更有利的毒性特征。

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引用次数: 0

Revolutionizing lung cancer treatment: Introducing PROTAC therapy as a novel paradigm in targeted therapeutics 革命性的肺癌治疗：引入PROTAC治疗作为靶向治疗的新范式。

IF 2.5 4区医学 Q3 ONCOLOGY

Current Problems in Cancer

Pub Date : 2025-02-01 DOI: 10.1016/j.currproblcancer.2024.101172

Atharva Mahajan , Gauri Panzade , Tiyasa Bhuniya , Purbasha Das , Bidyabati Bhattacharjee , Sagnik Das , Ankita Chowdhury , Kashmira Chakraborty , Sudeepta Guha , Anushka Samant , Anuvab Dey , Subhrojyoti Ghosh

This comprehensive review explores the transformative potential of PROTAC (Proteolysis-Targeting Chimeras) therapy as a groundbreaking approach in the landscape of lung cancer treatment. The introduction provides a succinct overview of current challenges in lung cancer treatment, emphasizing the significance of targeted therapies. Focusing on PROTAC therapy, the article elucidates its mechanism of action, comparing it with traditional targeted therapies and highlighting the key components and design principles of PROTAC molecules. In the context of lung cancer, the review meticulously summarizes preclinical evidence, emphasizing efficacy and specificity gleaned from studies evaluating PROTAC therapy. It delves into the implications of this preclinical data, discussing potential advantages over existing targeted therapies. An update on ongoing clinical trials involving PROTAC therapy for lung cancer offers a snapshot of the current progress, with a summary of key outcomes and advancements in early-phase trials. The mechanistic insights into PROTAC therapy's impact on lung cancer cells are explored, alongside a discussion on potential biomarkers for patient stratification and response prediction. The influence of tumor heterogeneity on PROTAC therapy outcomes is also addressed. Safety and tolerability assessments, encompassing preclinical and clinical studies, are comprehensively evaluated, including a comparative analysis with traditional targeted therapies and strategies to mitigate side effects. Looking forward, the article discusses the future perspectives of PROTAC therapy in lung cancer treatment and addresses ongoing challenges, providing a nuanced exploration of potential combination therapies and synergistic approaches. In conclusion, the review summarizes key findings and insights, underscoring the tremendous potential of PROTAC therapy as a promising and innovative avenue in pursuing more effective lung cancer treatments.

这篇全面的综述探讨了PROTAC（蛋白水解靶向嵌合体）疗法作为肺癌治疗领域的一种突破性方法的变革潜力。引言简要概述了当前肺癌治疗面临的挑战，强调了靶向治疗的重要性。本文以PROTAC治疗为重点，阐述了其作用机制，并与传统靶向治疗进行了比较，重点介绍了PROTAC分子的关键成分和设计原则。在肺癌的背景下，该综述精心总结了临床前证据，强调了从评估PROTAC治疗的研究中收集到的疗效和特异性。它深入研究了这些临床前数据的含义，讨论了相对于现有靶向治疗的潜在优势。正在进行的涉及PROTAC治疗肺癌的临床试验的最新情况提供了当前进展的快照，并总结了早期试验的主要结果和进展。本文探讨了PROTAC治疗对肺癌细胞影响的机制，并讨论了用于患者分层和反应预测的潜在生物标志物。肿瘤异质性对PROTAC治疗结果的影响也被讨论。安全性和耐受性评估，包括临床前和临床研究，全面评估，包括与传统靶向治疗和减轻副作用策略的比较分析。展望未来，本文讨论了PROTAC治疗在肺癌治疗中的未来前景，并解决了当前的挑战，提供了潜在的联合治疗和协同方法的细致探索。总之，本综述总结了主要发现和见解，强调了PROTAC治疗作为一种有前景的创新途径在寻求更有效的肺癌治疗方面的巨大潜力。

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引用次数: 0

Immune checkpoint expression and therapeutic implications in IDH1-mutant and wild-type glioblastomas 免疫检查点在idh1突变型和野生型胶质母细胞瘤中的表达及其治疗意义。

IF 2.5 4区医学 Q3 ONCOLOGY

Current Problems in Cancer

Pub Date : 2025-01-25 DOI: 10.1016/j.currproblcancer.2025.101182

Avaniyapuram Kannan Murugan , Siddarth Kannan , Ali S. Alzahrani

Programmed cell death protein 1 (PDCD1) and cluster of differentiation 274 (CD274) expression is implicated in escaping tumors from immune surveillance. Immune checkpoint inhibitors show promise in cancer therapy, yet their efficacy in glioblastomas, particularly with IDH1 mutations, remains unclear. This study analyzed two independent NGS datasets (n = 577 and n = 153) from TCGA to investigate the expression of PDCD1 and CD274 in glioblastomas and their relationship with IDH1 mutations. We used cBioPortal for mutation analysis, RNA seq for expression analysis, miRDB and miRabel for differential expression of miRNAs, and Kaplan-Meier for survival prediction. We found that 5.4% of glioblastomas harbored IDH1 mutations, correlating with improved overall survival (OS) (p = 2.196e-3). Different glioblastoma cohorts showed a diverse IDH1 mutational prevalence (4-31%). Despite this, IDH1^Mu was consistently associated with better OS (p = 8.235e-5). Notably, PDCD1 and CD274 were statistically significantly highly expressed in both IDH1^Wt (p < 0.0001) and IDH1^Mu tumors (p < 0.0001), with higher expression linked to poorer survival outcomes (PDCD1: p = 0.009; CD274: p = 0.02). Differential co-expression analyses revealed distinct gene and miRNA profiles for IDH1^Wt and IDH1^Mu glioblastomas, with specific upregulation of PTEN and downregulation of MUC16 in IDH1^Wt, and upregulation of PIK3R1 in IDH1^Mu. Additionally, PIK3R1 and ITGB2 emerged as critical druggable targets. Our findings indicate that PDCD1 and CD274 are highly expressed irrespective of IDH1 mutation statuses, suggesting that glioblastomas could benefit from immunotherapy. Moreover, IDH1^Mu glioblastomas may require a combination of PI3K/AKT/mTOR inhibitors and immunotherapy due to PIK3R1 overexpression.

程序性细胞死亡蛋白1（PDCD1）和分化簇274（CD274）的表达与肿瘤逃避免疫监视有关。免疫检查点抑制剂在癌症治疗中大有可为，但它们在胶质母细胞瘤（尤其是 IDH1 突变的胶质母细胞瘤）中的疗效仍不明确。本研究分析了来自 TCGA 的两个独立 NGS 数据集（n = 577 和 n = 153），以研究 PDCD1 和 CD274 在胶质母细胞瘤中的表达及其与 IDH1 突变的关系。我们使用 cBioPortal 进行突变分析，使用 RNA seq 进行表达分析，使用 miRDB 和 miRabel 进行 miRNAs 差异表达分析，使用 Kaplan-Meier 进行生存预测。我们发现，5.4%的胶质母细胞瘤携带IDH1突变，这与总生存率（OS）的提高相关（p = 2.196e-3）。不同的胶质母细胞瘤队列显示出不同的IDH1突变发生率（4-31%）。尽管如此，IDH1Mu 始终与较好的 OS 相关（p = 8.235e-5）。值得注意的是，PDCD1和CD274在IDH1Wt（p＜0.0001）和IDH1Mu肿瘤（p＜0.0001）中都有显著的高表达，表达越高，生存结果越差（PDCD1：p = 0.009；CD274：p = 0.02）。差异共表达分析显示，IDH1Wt和IDH1Mu胶质母细胞瘤的基因和miRNA谱不同，IDH1Wt中PTEN特异性上调，MUC16下调，而IDH1Mu中PIK3R1上调。此外，PIK3R1 和 ITGB2 成为关键的药物靶点。我们的研究结果表明，无论IDH1突变状态如何，PDCD1和CD274都高度表达，这表明胶质母细胞瘤可从免疫疗法中获益。此外，由于PIK3R1的过度表达，IDH1Mu胶质母细胞瘤可能需要联合使用PI3K/AKT/mTOR抑制剂和免疫疗法。

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引用次数: 0

Efficacy and safety of gene therapy approaches for malignant gliomas: A systematic review and meta-analysis 恶性胶质瘤基因治疗方法的疗效和安全性：一项系统回顾和荟萃分析：nrnr22.5 nrnr1011.413.511.9 nrnrnr。

IF 2.5 4区医学 Q3 ONCOLOGY

Current Problems in Cancer

Pub Date : 2025-01-23 DOI: 10.1016/j.currproblcancer.2025.101183

Elnaz Amanzadeh Jajin, Saeed Oraee-Yazdani, Alireza Zali, Roozbeh Tavanaei

Background

Malignant gliomas are the most aggressive brain tumors with no certain therapeutic methods. Nowadays, novel treatment methods are introduced for gliomas among which gene therapy is known as a promising and robust method. In this method, genes with key roles in the prevention of cell cycle or induction of cell suicide are transferred to the tumor site using vectors. Viral vectors are the most popular transfer methods, while the liposomes are also used for gene therapy.

Methods

This meta-analysis and systematic review was performed based on PRISMA guidelines. We performed a comprehensive search in databases including PubMed, Embase, and clinicaltrial.gov. After processing and filtering the articles, phase 1 clinical trials were chosen for the evaluation of the efficacy and safety of gene therapy for malignant gliomas.

Results

The obtained results showed that gene therapy increases overall survival (OS) and progression-free survival (PFS) in two years of follow-up. Subgroup analysis also showed that cytokines exhibit the highest effectiveness compared to suicide genes and oncolytic genes. It was found that gene therapy is more efficient for recurrent gliomas than primary gliomas. The subgroup analysis for vectors revealed that Adenovirus is the most effective for increasing the OS in malignant glioma patients.

Conclusion

Gene therapy is an immunotherapy method for malignant gliomas following the standard treatment approach. Considering the effectiveness of gene therapy on the survival of patients, it is hoped that solving related issues with gene therapy will help to increase the OS rate in this malignant disease.

背景：恶性胶质瘤是最具侵袭性的脑肿瘤，目前尚无特定的治疗方法。近年来，神经胶质瘤的治疗方法越来越多，其中基因治疗被认为是一种很有前途的治疗方法。在这种方法中，利用载体将在预防细胞周期或诱导细胞自杀中起关键作用的基因转移到肿瘤部位。病毒载体是最流行的转移方法，而脂质体也用于基因治疗。方法：根据PRISMA指南进行meta分析和系统评价。我们在PubMed、Embase和clinicaltrial.gov等数据库中进行了全面的搜索。对文章进行处理和筛选后，选择1期临床试验，评价基因治疗恶性胶质瘤的疗效和安全性。结果：获得的结果显示，基因治疗在两年的随访中提高了总生存期（OS）和无进展生存期（PFS）。亚组分析还显示，细胞因子比自杀基因和溶瘤基因表现出最高的有效性。研究发现基因治疗复发性胶质瘤比原发性胶质瘤更有效。载体亚群分析显示，腺病毒对提高恶性胶质瘤患者OS最有效。结论：基因治疗是恶性胶质瘤继标准治疗方法后的一种免疫治疗方法。考虑到基因治疗对患者生存的影响，希望通过基因治疗解决相关问题，有助于提高这种恶性疾病的OS率。

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引用次数: 0

Information for Readers 读者资讯

IF 2.5 4区医学 Q3 ONCOLOGY

Current Problems in Cancer

Pub Date : 2024-12-01 DOI: 10.1016/S0147-0272(24)00105-3

引用次数: 0

Title Page 标题页

IF 2.5 4区医学 Q3 ONCOLOGY

Current Problems in Cancer

Pub Date : 2024-12-01 DOI: 10.1016/S0147-0272(24)00104-1

引用次数: 0

Dietary influence on cancer progression: Gut health and genomic profiles 饮食对癌症进展的影响：肠道健康和基因组谱

IF 2.5 4区医学 Q3 ONCOLOGY

Current Problems in Cancer

Pub Date : 2024-11-29 DOI: 10.1016/j.currproblcancer.2024.101159

Yashar Vaziri

This scholarly review comprehensively examines the connection between dietary habits, gut health, cancer prognosis, and genomic profiles. It emphasizes the crucial role of gut microbiota in mediating genomic changes and oncogenic processes through metabolic derivatives.It advocatеs for pеrsonalizеd nutrition stratеgiеs based on individual microbiomе and gеnomic profilеs and proposеs that customized diеtary intеrvеntions could play a crucial rolе in cancеr prеvеntion thеrapy. Thе article highlights thе influеncе of spеcific nutriеnts and such as diеtary fibеr and polyphеnols found in cеrtain foods and dеmonstrating thеir potеntial to altеr gеnе еxprеssions associatеd with inflammation and tumorigеnеsis. Thе rеviеw citеs rеcеnt studiеs that support thе idеa that diеtary modifications can influеncе gеnе rеgulation and thеrеby potеntially altеring cancеr progrеssion. Nevertheless, it calls for morе rigorous rеsеarch including longitudinal and randomizеd studies, to substantiatе thе еvidеncе nеcеssary for developing diеtary guidеlinеs tailorеd for cancеr patiеnts. Thе rеviеw еmphasizеs thе nееd for a multidisciplinary approach and highlight thе importancе of collaboration across thе fiеlds of nutrition gеnomics microbiology and oncology to improve cancеr trеatmеnts and patiеnt quality of lifе. It posits thе rеviеw as a cornеrstonе for a divеrsе audiеncе within thе scientific and mеdical communitimphasizing thе nеcеssity for ongoing rеsеarch in nutritional gеnomics which it dеpicts as a fiеld full of opportunitiеs to transform cancеr carе.

这篇学术综述全面考察了饮食习惯、肠道健康、癌症预后和基因组图谱之间的联系。它强调肠道微生物群在通过代谢衍生物介导基因组变化和致癌过程中的关键作用。它倡导基于个体微生物和基因组图谱的个人个性化营养策略，并提出定制的个人营养策略可以在癌症预防治疗中发挥重要作用。这篇文章强调了特定营养成分的影响，例如在某些食物中发现的膳食纤维和多酚，并论证了与炎症和肿瘤相关的膳食纤维和多酚的影响。支持如下观点的数据库：数据库的修改可以影响数据库的修改，数据库的修改可以改变数据库的修改，数据库的修改可以改变数据库的修改。尽管如此，它需要更严格的数据研究，包括纵向和随机研究，以证实该数据库用于开发针对癌症患者量身定制的数据指南。该研究强调了该研究的多学科方法，并强调了营养经济学、微生物学和肿瘤学五个领域之间合作的重要性，以改善癌症治疗和患者的生活质量。它将生态环境假设为科学和医学社区中一个生态环境的生态环境，强调了生态环境对营养经济学中正在进行的生态环境的生态环境的生态环境，并将其描述为一个充满机会的生态环境来改变癌症生态环境。

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引用次数: 0

Technological innovations enhancing palliative care in cancer: A new era of patient care in India 加强癌症姑息治疗的技术创新：印度患者护理的新时代

IF 2.5 4区医学 Q3 ONCOLOGY

Current Problems in Cancer

Pub Date : 2024-11-24 DOI: 10.1016/j.currproblcancer.2024.101158

Snehasish Tripathy, Sapna Negi, Ankita Mathur, Vini Mehta

引用次数: 0

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