Cancer and Metastasis Reviews最新文献_第3页

LGR5: An emerging therapeutic target for cancer metastasis and chemotherapy resistance. LGR5：肿瘤转移和化疗耐药的新靶点

IF 7.7 2区医学

Cancer and Metastasis Reviews Pub Date : 2025-01-17 DOI: 10.1007/s10555-024-10239-x

Wanqi Wang, Noor A Lokman, Simon C Barry, Martin K Oehler, Carmela Ricciardelli

{"title":"LGR5: An emerging therapeutic target for cancer metastasis and chemotherapy resistance.","authors":"Wanqi Wang, Noor A Lokman, Simon C Barry, Martin K Oehler, Carmela Ricciardelli","doi":"10.1007/s10555-024-10239-x","DOIUrl":"10.1007/s10555-024-10239-x","url":null,"abstract":"Cancer stem cells play an important role in tumor progression and chemotherapy resistance. Leucine-rich G repeat-containing protein-coupled receptor 5 (LGR5) has been identified as a cancer stem cell marker in several cancer types. LGR5 is involved in cancer development and progression via several pathways including WNT/β-catenin signaling pathway. LGR5 plays a role in tumor progression by promoting cancer cell migration, invasion, metastasis, and angiogenesis in many cancers including colorectal, brain, gastric, and ovarian cancer. This review summarises the current knowledge on the expression and functional role of LGR5 in cancers, the molecular mechanisms regulated by LGR5, and the relationship between LGR5 and chemotherapy resistance. The review also includes highlights potential strategies to inhibit LGR5 expression and function. The majority of functional studies have shown that LGR5 plays an important role in promoting cancer progression, metastasis and chemotherapy resistance however, in some contexts LGR5 can also activate tumor-suppressive pathways and LGR5 negative cells can also promote cancer progression. The review highlights that targeting LGR5 is a promising anti-cancer treatment but the functional effect of LGR5 on tumor cells is complex may be dependent on cancer type, tumor microenvironment and cross-talk with other molecules in the LGR5 signaling pathway.","PeriodicalId":9489,"journal":{"name":"Cancer and Metastasis Reviews","volume":"44 1","pages":"23"},"PeriodicalIF":7.7,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The transcription factor FOXQ1 in cancer. 癌症中的转录因子FOXQ1。

IF 7.7 2区医学

Cancer and Metastasis Reviews Pub Date : 2025-01-08 DOI: 10.1007/s10555-025-10240-y

Stefan Koch

引用次数: 0

Neuropeptide Y in cancer-biological functions and potential clinical implications. 神经肽Y在癌症生物学功能和潜在的临床意义。

IF 7.7 2区医学

Cancer and Metastasis Reviews Pub Date : 2025-01-06 DOI: 10.1007/s10555-024-10237-z

Dawid Sigorski, Aleksandra Sejda, Nouran Abualsaud, Ewa Krawczyk, Ewa Izycka-Swieszewska, Joanna Kitlinska

{"title":"Neuropeptide Y in cancer-biological functions and potential clinical implications.","authors":"Dawid Sigorski, Aleksandra Sejda, Nouran Abualsaud, Ewa Krawczyk, Ewa Izycka-Swieszewska, Joanna Kitlinska","doi":"10.1007/s10555-024-10237-z","DOIUrl":"10.1007/s10555-024-10237-z","url":null,"abstract":"Neuropeptide Y (NPY) is a sympathetic neurotransmitter widely distributed in the peripheral and central nervous system, affecting many physiological functions. Consequently, dysregulation of the NPY system contributes to numerous pathological disorders, including stress, obesity, and cancer. The pleiotropic functions of NPY in humans are mediated by G protein-coupled receptors (Y1R, Y2R, Y5R), which activate several signaling pathways and thereby regulate cell growth, differentiation, apoptosis, proliferation, angiogenesis, and metabolism. These activities of NPY are highly relevant to tumor biology and known hallmarks of cancer, including sustained proliferative potential, resisting cell death, angiogenesis, invasion, and metastases. In this comprehensive review, we describe the cellular functions of NPY and discuss its role in cancer pathobiology, as well as provide the current state of knowledge pertaining to NPY and its receptors in various cancer types. Moreover, we focus on potential clinical applications targeting the NPY system, such as its role as a prognostic and predictive factor, as well as its utility in cancer diagnostics, imaging, and treatment. Altogether, growing evidence supports the significant role of the NPY system in tumor pathobiology and implicates its potential therapeutic and diagnostic value in modern oncology.","PeriodicalId":9489,"journal":{"name":"Cancer and Metastasis Reviews","volume":"44 1","pages":"21"},"PeriodicalIF":7.7,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11703900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Recapitulating the potential contribution of protein S-palmitoylation in cancer. 概述s -棕榈酰化蛋白在癌症中的潜在作用。

IF 7.7 2区医学

Cancer and Metastasis Reviews Pub Date : 2024-12-27 DOI: 10.1007/s10555-024-10217-3

Suchi Chaturvedi, Avinash Sonawane

{"title":"Recapitulating the potential contribution of protein S-palmitoylation in cancer.","authors":"Suchi Chaturvedi, Avinash Sonawane","doi":"10.1007/s10555-024-10217-3","DOIUrl":"10.1007/s10555-024-10217-3","url":null,"abstract":"Protein S-palmitoylation is a reversible form of protein lipidation in which the formation of a thioester bond occurs between a cysteine (Cys) residue of a protein and a 16-carbon fatty acid chain. This modification is catalyzed by a family of palmitoyl acyl transferases, the DHHC enzymes, so called because of their Asp-His-His-Cys (DHHC) catalytic motif. Deregulation of DHHC enzymes has been linked to various diseases, including cancer and infections. Cancer, a major cause of global mortality, is characterized by features like uncontrolled cell growth, resistance to cell death, angiogenesis, invasion, and metastasis. Several of these processes are controlled by DHHC-mediated S-palmitoylation of oncogenes or tumor suppressors, including growth factor receptors (e.g., EGFR), kinases (e.g., AKT), and transcription factors (e.g., β-catenin). Dynamic regulation of S-palmitoylation is also governed by protein depalmitoylases. These enzymes balance the cycling of palmitoylation and regulate cellular signaling, cell growth, and its organization. Given the significance of S-palmitoylation in cancer, the DHHCs and protein depalmitoylases are promising targets for cancer therapy. Here we summarize the catalytic mechanisms of DHHC enzymes and depalmitoylases, their role in cancer progression and prevention, as well as the crosstalk of palmitoylation with other post-translational modifications. Additionally, we discuss the methods to detect S-palmitoylation, the limitations of available DHHC-targeting inhibitors, and ongoing research efforts to address these obstacles.","PeriodicalId":9489,"journal":{"name":"Cancer and Metastasis Reviews","volume":"44 1","pages":"20"},"PeriodicalIF":7.7,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Homologous recombination deficiency (HRD) diagnostics: underlying mechanisms and new perspectives. 同源重组缺陷（HRD）诊断：潜在机制和新观点。

IF 7.7 2区医学

Cancer and Metastasis Reviews Pub Date : 2024-12-26 DOI: 10.1007/s10555-024-10238-y

Andrey Kechin, Maksim Koryukov, Regina Mikheeva, Maksim Filipenko

{"title":"Homologous recombination deficiency (HRD) diagnostics: underlying mechanisms and new perspectives.","authors":"Andrey Kechin, Maksim Koryukov, Regina Mikheeva, Maksim Filipenko","doi":"10.1007/s10555-024-10238-y","DOIUrl":"10.1007/s10555-024-10238-y","url":null,"abstract":"Homologous recombination deficiency (HRD) is considered a universal and effective sign of a tumor's sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors. HRD diagnostics have undergone several stages of transformations: from detection of point mutations in HR-related genes and large regions with loss of heterozygosity detected using single-nucleotide polymorphism arrays to whole-genome signatures of single-nucleotide variants, large genomic rearrangements (LGRs), and copy number alterations. All these methods have their own advantages and limitations. HRD tests, based on signatures of LGRs and copy number alterations, show in hindsight that some progenitor cells have possessed HRD status but not the current state of the genome. The aim of this review was to compare different methods of HRD detection and mechanisms of formation of HRD-specific LGRs. In the last several years, new data appeared implying a crucial role of proteins BRCA1 and BRCA2 in the resolution of stalled replication forks that may be associated with at least some of LGRs observed in HRD-positive tumors. Reviewing current knowledge on these mechanisms, distributions of different LGR types, and limitations of sequencing technologies and algorithms of data analysis, we offer some new perspectives on HRD diagnostics. We hope that this review will help to accelerate the development of new diagnostic approaches in this important field of molecular oncology.","PeriodicalId":9489,"journal":{"name":"Cancer and Metastasis Reviews","volume":"44 1","pages":"19"},"PeriodicalIF":7.7,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Influence of antibody-drug conjugate cleavability, drug-to-antibody ratio, and free payload concentration on systemic toxicities: A systematic review and meta-analysis. 抗体-药物共轭物的可裂解性、药物-抗体比率和游离有效载荷浓度对全身毒性的影响：系统回顾与荟萃分析。

IF 7.7 2区医学

Cancer and Metastasis Reviews Pub Date : 2024-12-20 DOI: 10.1007/s10555-024-10231-5

Shou-Ching Tang, Carrie Wynn, Tran Le, Martin McCandless, Yunxi Zhang, Ritesh Patel, Nita Maihle, William Hillegass

{"title":"Influence of antibody-drug conjugate cleavability, drug-to-antibody ratio, and free payload concentration on systemic toxicities: A systematic review and meta-analysis.","authors":"Shou-Ching Tang, Carrie Wynn, Tran Le, Martin McCandless, Yunxi Zhang, Ritesh Patel, Nita Maihle, William Hillegass","doi":"10.1007/s10555-024-10231-5","DOIUrl":"10.1007/s10555-024-10231-5","url":null,"abstract":"While in theory antibody drug conjugates (ADCs) deliver high-dose chemotherapy directly to target cells, numerous side effects are observed in clinical practice. We sought to determine the effect of linker design (cleavable versus non-cleavable), drug-to-antibody ratio (DAR), and free payload concentration on systemic toxicity. Two systematic reviews were performed via PubMed search of clinical trials published between January 1998-July 2022. Eligible studies: (1) clinical trial for cancer therapy in adults, (2) ≥ 1 study arm included a single-agent ADC, (3) ADC used was commercially available/FDA-approved. Data was extracted and pooled using generalized linear mixed effects logistic models. 40 clinical trials involving 7,879 patients from 11 ADCs, including 9 ADCs with cleavable linkers (N = 2,985) and 2 with non-cleavable linkers (N = 4,894), were included. Significantly more composite adverse events (AEs) ≥ grade 3 occurred in patients in the cleavable linkers arm (47%) compared with the non-cleavable arm (34%). When adjusted for DAR, for grade ≥ 3 toxicities, non-cleavable linkers remained independently associated with lower toxicity for any AE (p = 0.002). Higher DAR was significantly associated with higher probability of grade ≥ 3 toxicity for any AE. There was also a significant interaction between cleavability status and DAR for any AE (p = 0.002). Finally, higher measured systemic free payload concentrations were significantly associated with higher DARs (p = 0.043). Our results support the hypothesis that ADCs with cleavable linkers result in premature payload release, leading to increased systemic free payload concentrations and associated toxicities. This may help to inform future ADC design and rational clinical application.","PeriodicalId":9489,"journal":{"name":"Cancer and Metastasis Reviews","volume":"44 1","pages":"18"},"PeriodicalIF":7.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11662062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evolving strategies for addressing CAR T-cell toxicities. 解决 CAR T 细胞毒性问题的策略不断发展。

IF 7.7 2区医学

Cancer and Metastasis Reviews Pub Date : 2024-12-15 DOI: 10.1007/s10555-024-10227-1

Alexander W Rankin, Brynn B Duncan, Cecily Allen, Sara K Silbert, Nirali N Shah

引用次数: 0

TRIM-endous functional network of tripartite motif 29 (TRIM29) in cancer progression and beyond. trim3 - motif 29 （TRIM29）在癌症进展及其后的内源功能网络。

IF 7.7 2区医学

Cancer and Metastasis Reviews Pub Date : 2024-12-07 DOI: 10.1007/s10555-024-10226-2

Qitong Wu, Deeptashree Nandi, Dipali Sharma

{"title":"TRIM-endous functional network of tripartite motif 29 (TRIM29) in cancer progression and beyond.","authors":"Qitong Wu, Deeptashree Nandi, Dipali Sharma","doi":"10.1007/s10555-024-10226-2","DOIUrl":"10.1007/s10555-024-10226-2","url":null,"abstract":"While most Tripartite motif (TRIM) family proteins are E3 ubiquitin ligases, some members have functions beyond the regulation of ubiquitination, impacting normal physiological processes and disease progression. TRIM29, an important member of the TRIM family, exerts a predominant influence on cancer growth, epithelial-to-mesenchymal transition, stemness and metastatic progression by directly potentiating multiple canonical oncogenic pathways. The cancer-promoting effect of TRIM29 is also evident in metabolic interventions and interference with the efficacy of cancer therapeutics. As expected for any key node in cancer, the expression of TRIM29 is tightly regulated by non-coding RNAs, epigenetic modulation, and post-translational regulation. A systematic discussion of how TRIM29 is regulated in cancer, its influences on cancer progression, and its impact on cancer therapeutics is presented in this review. We also explore the context-dependent alterations between TRIM29 function from oncogenic to tumor suppression. As TRIM29 is involved in multiple aspects of cancer progression, a better understanding of its biological impact in cancer may help improve prognosis and develop novel therapeutic combinations, leading to improved personalized cancer care.","PeriodicalId":9489,"journal":{"name":"Cancer and Metastasis Reviews","volume":"44 1","pages":"16"},"PeriodicalIF":7.7,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11625080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CAR T-cell therapy to treat multiple myeloma: current state and future directions. CAR - t细胞疗法治疗多发性骨髓瘤：现状与未来方向

IF 7.7 2区医学

Cancer and Metastasis Reviews Pub Date : 2024-12-03 DOI: 10.1007/s10555-024-10219-1

Siddhartha Thammineni Reddy, Hitomi Hosoya, Lekha Mikkilineni

{"title":"CAR T-cell therapy to treat multiple myeloma: current state and future directions.","authors":"Siddhartha Thammineni Reddy, Hitomi Hosoya, Lekha Mikkilineni","doi":"10.1007/s10555-024-10219-1","DOIUrl":"10.1007/s10555-024-10219-1","url":null,"abstract":"Chimeric antigen receptor (CAR) T-cell therapy represents a transformative advancement in treating relapsed or refractory multiple myeloma (MM) in both early- and late-line settings. MM, a plasma cell malignancy, traditionally requires ongoing complex drug regimens, posing significant burdens on patients. In contrast, CAR T-cell therapy offers a one-time treatment option without the need for continuous maintenance therapy. CAR T-cell therapy leverages engineered T-cells to target specific antigens on tumor cells, leading to their elimination. Current approved therapies target B-cell maturation antigen (BCMA); new targets are under investigation, such as G-protein-coupled receptor class C group 5 member D (GPRC5D). Despite its efficacy, CAR T-cell therapy is associated with serious toxicities such as cytokine release syndrome (CRS) and immune-effector cell-associated neurotoxicity syndrome (ICANS), necessitating careful management. The review will provide an overview of the design and manufacturing of CAR T-cells and current FDA indications, as well as challenges and future directions of CAR-T therapy for MM treatment.","PeriodicalId":9489,"journal":{"name":"Cancer and Metastasis Reviews","volume":"44 1","pages":"14"},"PeriodicalIF":7.7,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correlative studies reveal factors contributing to successful CAR-T cell therapies in cancer. 相关研究揭示了CAR-T细胞治疗癌症成功的因素。

IF 7.7 2区医学

Cancer and Metastasis Reviews Pub Date : 2024-12-03 DOI: 10.1007/s10555-024-10232-4

Catherine D Yao, Kara L Davis

{"title":"Correlative studies reveal factors contributing to successful CAR-T cell therapies in cancer.","authors":"Catherine D Yao, Kara L Davis","doi":"10.1007/s10555-024-10232-4","DOIUrl":"10.1007/s10555-024-10232-4","url":null,"abstract":"Cellular and targeted immunotherapies have revolutionized cancer treatments in the last several decades. Successful cellular therapies require both effective and durable cytotoxic activity from the immune cells as well as an accessible and susceptible response from targeted cancer cells. Correlative studies from clinical trials as well as real-world data from FDA-approved therapies have revealed invaluable insights about immune cell factors and cancer cell factors that impact rates of response and relapse to cellular therapies. This review focuses on the flagship cellular therapy of engineered chimeric antigen receptor T-cells (CAR-T cells). Within the CAR-T cell compartment, we discuss discoveries about T-cell phenotype, transcriptome, epigenetics, cytokine signaling, and metabolism that inform the cell manufacturing process to produce the most effective and durable CAR-T cells. Within the cancer cell compartment, we discuss mechanisms of resistance and relapse caused by mutations, alternative splicing, post-transcriptional modifications, and cellular reprogramming. Continued correlative and mechanistic studies are required to help us further optimize cellular therapies in a variety of malignancies.","PeriodicalId":9489,"journal":{"name":"Cancer and Metastasis Reviews","volume":"44 1","pages":"15"},"PeriodicalIF":7.7,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0