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Targeting MYC Proteins for Tumor Therapy 靶向MYC蛋白用于肿瘤治疗
IF 7.7 2区 医学
Annual Review of Cancer Biology-Series Pub Date : 2020-03-09 DOI: 10.1146/annurev-cancerbio-030518-055826
E. Wolf, M. Eilers
{"title":"Targeting MYC Proteins for Tumor Therapy","authors":"E. Wolf, M. Eilers","doi":"10.1146/annurev-cancerbio-030518-055826","DOIUrl":"https://doi.org/10.1146/annurev-cancerbio-030518-055826","url":null,"abstract":"Targeting the function of MYC oncoproteins holds the promise of achieving conceptually new and effective anticancer therapies that can be applied to a broad range of tumors. The nature of the target however—a broadly, possibly universally acting transcription factor that has no enzymatic activity and is largely unstructured unless complexed with partner proteins—has so far defied the development of clinically applicable MYC-directed therapies. At the same time, lingering questions about exactly which functions of MYC proteins account for their pervasive oncogenic role in human tumors and need to be targeted have prevented the development of effective therapies using surrogate targets that act in critical MYC-dependent pathways. In this review, we therefore argue that rigorous testing of critical oncogenic functions and protein/protein interactions and new chemical approaches to target them are necessary to successfully eradicate MYC-driven tumors.","PeriodicalId":54233,"journal":{"name":"Annual Review of Cancer Biology-Series","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2020-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1146/annurev-cancerbio-030518-055826","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41941389","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: 40
The Neural Regulation of Cancer 癌症的神经调节
IF 7.7 2区 医学
Annual Review of Cancer Biology-Series Pub Date : 2020-03-09 DOI: 10.1146/annurev-cancerbio-030419-033349
Shawn M. Gillespie, M. Monje
{"title":"The Neural Regulation of Cancer","authors":"Shawn M. Gillespie, M. Monje","doi":"10.1146/annurev-cancerbio-030419-033349","DOIUrl":"https://doi.org/10.1146/annurev-cancerbio-030419-033349","url":null,"abstract":"The nervous system is intimately involved in physiological processes from development and growth to tissue homeostasis and repair throughout the body. It logically follows that the nervous system has the potential to play analogous roles in the context of cancer. Progress toward understanding the crucial role of the nervous system in cancer has accelerated in recent years, but much remains to be learned. Here, we highlight rapidly evolving concepts in this burgeoning research space and consider next steps toward understanding and therapeutically targeting the neural regulation of cancer.","PeriodicalId":54233,"journal":{"name":"Annual Review of Cancer Biology-Series","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2020-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1146/annurev-cancerbio-030419-033349","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46598281","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: 10
Immune-Based Approaches for the Treatment of Pediatric Malignancies. 儿童恶性肿瘤的免疫治疗
IF 7.7 2区 医学
Annual Review of Cancer Biology-Series Pub Date : 2020-03-01 DOI: 10.1146/annurev-cancerbio-030419-033436
Kristopher R Bosse, Robbie G Majzner, Crystal L Mackall, John M Maris
{"title":"Immune-Based Approaches for the Treatment of Pediatric Malignancies.","authors":"Kristopher R Bosse,&nbsp;Robbie G Majzner,&nbsp;Crystal L Mackall,&nbsp;John M Maris","doi":"10.1146/annurev-cancerbio-030419-033436","DOIUrl":"https://doi.org/10.1146/annurev-cancerbio-030419-033436","url":null,"abstract":"<p><p>Immune-based therapies have now been credentialed for pediatric cancers with the robust efficacy of chimeric antigen receptor (CAR) T cells for pediatric B cell acute lymphocytic leukemia (ALL), offering a chance of a cure for children with previously lethal disease and a potentially more targeted therapy to limit treatment-related morbidities. The developmental origins of most pediatric cancers make them ideal targets for immune-based therapies that capitalize on the differential expression of lineage-specific cell surface molecules such as antibodies, antibody-drug conjugates, or CAR T cells, while the efficacy of other therapies that depend on tumor immunogenicity such as immune checkpoint inhibitors has been limited to date. Here we review the current status of immune-based therapies for childhood cancers, discuss challenges to developing immunotherapeutics for these diseases, and outline future directions of pediatric immunotherapy discovery and development.</p>","PeriodicalId":54233,"journal":{"name":"Annual Review of Cancer Biology-Series","volume":"4 ","pages":"353-370"},"PeriodicalIF":7.7,"publicationDate":"2020-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1146/annurev-cancerbio-030419-033436","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39002795","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: 9
Investigating Tumor Heterogeneity in Mouse Models. 研究小鼠模型中的肿瘤异质性。
IF 7.7 2区 医学
Annual Review of Cancer Biology-Series Pub Date : 2020-03-01 Epub Date: 2019-11-06 DOI: 10.1146/annurev-cancerbio-030419-033413
Tuomas Tammela, Julien Sage
{"title":"Investigating Tumor Heterogeneity in Mouse Models.","authors":"Tuomas Tammela, Julien Sage","doi":"10.1146/annurev-cancerbio-030419-033413","DOIUrl":"10.1146/annurev-cancerbio-030419-033413","url":null,"abstract":"<p><p>Cancer arises from a single cell through a series of acquired mutations and epigenetic alterations. Tumors gradually develop into a complex tissue comprised of phenotypically heterogeneous cancer cell populations, as well as noncancer cells that make up the tumor microenvironment. The phenotype, or state, of each cancer and stromal cell is influenced by a plethora of cell-intrinsic and cell-extrinsic factors. The diversity of these cellular states promotes tumor progression, enables metastasis, and poses a challenge for effective cancer treatments. Thus, the identification of strategies for the therapeutic manipulation of tumor heterogeneity would have significant clinical implications. A major barrier in the field is the difficulty in functionally investigating heterogeneity in tumors in cancer patients. Here we review how mouse models of human cancer can be leveraged to interrogate tumor heterogeneity and to help design better therapeutic strategies.</p>","PeriodicalId":54233,"journal":{"name":"Annual Review of Cancer Biology-Series","volume":"4 1","pages":"99-119"},"PeriodicalIF":7.7,"publicationDate":"2020-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39102932","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 Epithelial-to-Mesenchymal Transition (EMT) in Development and Cancer. 上皮-间质转化(EMT)在发育和癌症中的作用。
IF 7.7 2区 医学
Annual Review of Cancer Biology-Series Pub Date : 2020-03-01 Epub Date: 2019-11-25 DOI: 10.1146/annurev-cancerbio-030518-055425
Alexandre Francou, Kathryn V Anderson
{"title":"The Epithelial-to-Mesenchymal Transition (EMT) in Development and Cancer.","authors":"Alexandre Francou,&nbsp;Kathryn V Anderson","doi":"10.1146/annurev-cancerbio-030518-055425","DOIUrl":"https://doi.org/10.1146/annurev-cancerbio-030518-055425","url":null,"abstract":"<p><p>Epithelial-to-mesenchymal transitions (EMTs) are complex cellular processes where cells undergo dramatic changes in signaling, transcriptional programming, and cell shape, while directing the exit of cells from the epithelium and promoting migratory properties of the resulting mesenchyme. EMTs are essential for morphogenesis during development and are also a critical step in cancer progression and metastasis formation. Here we provide an overview of the molecular regulation of the EMT process during embryo development, focusing on chick and mouse gastrulation and neural crest development. We go on to describe how EMT regulators participate in the progression of pancreatic and breast cancer in mouse models, and discuss the parallels with developmental EMTs and how these help to understand cancer EMTs. We also highlight the differences between EMTs in tumor and in development to arrive at a broader view of cancer EMT. We conclude by discussing how further advances in the field will rely on in vivo dynamic imaging of the cellular events of EMT.</p>","PeriodicalId":54233,"journal":{"name":"Annual Review of Cancer Biology-Series","volume":"4 ","pages":"197-220"},"PeriodicalIF":7.7,"publicationDate":"2020-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1146/annurev-cancerbio-030518-055425","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39002792","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: 26
Aiding and Abetting: How the Tumor Microenvironment Protects Cancer from Chemotherapy 辅助和教唆:肿瘤微环境如何保护癌症免受化疗
IF 7.7 2区 医学
Annual Review of Cancer Biology-Series Pub Date : 2019-03-04 DOI: 10.1146/ANNUREV-CANCERBIO-030518-055524
Eleanor R. C. Fiedler, M. Hemann
{"title":"Aiding and Abetting: How the Tumor Microenvironment Protects Cancer from Chemotherapy","authors":"Eleanor R. C. Fiedler, M. Hemann","doi":"10.1146/ANNUREV-CANCERBIO-030518-055524","DOIUrl":"https://doi.org/10.1146/ANNUREV-CANCERBIO-030518-055524","url":null,"abstract":"Disease recurrence following cancer therapy remains an intractable clinical problem and represents a major impediment to reducing the mortality attributable to malignant tumors. While research has traditionally focused on the cell-intrinsic mechanisms and mutations that render tumors refractory to both classical chemotherapeutics and targeted therapies, recent studies have begun to uncover myriad roles for the tumor microenvironment (TME) in modulating therapeutic efficacy. This work suggests that drug resistance is as much ecological as it is evolutionary. Specifically, cancers resident in organs throughout the body do not develop in isolation. Instead, tumor cells arise in the context of nonmalignant cellular components of a tissue. While the roles of these cell-extrinsic factors in cancer initiation and progression are well established, our understanding of the TME's influence on therapeutic outcome is in its infancy. Here, we focus on mechanisms by which neoplastic cells co-opt preexisting or treatment-induced signaling networks to survive chemotherapy.","PeriodicalId":54233,"journal":{"name":"Annual Review of Cancer Biology-Series","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2019-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1146/ANNUREV-CANCERBIO-030518-055524","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44351026","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: 10
Resistance to PARP Inhibitors: Lessons from Preclinical Models of BRCA-Associated Cancer PARP抑制剂耐药性：BRCA相关癌症临床前模型的经验教训
IF 7.7 2区 医学
Annual Review of Cancer Biology-Series Pub Date : 2019-03-04 DOI: 10.1146/ANNUREV-CANCERBIO-030617-050232
E. Gogola, S. Rottenberg, J. Jonkers
{"title":"Resistance to PARP Inhibitors: Lessons from Preclinical Models of BRCA-Associated Cancer","authors":"E. Gogola, S. Rottenberg, J. Jonkers","doi":"10.1146/ANNUREV-CANCERBIO-030617-050232","DOIUrl":"https://doi.org/10.1146/ANNUREV-CANCERBIO-030617-050232","url":null,"abstract":"Inhibitors of poly(ADP-ribose) polymerase (PARP) have recently entered the clinic for the treatment of homologous recombination–deficient cancers. Despite the success of this approach, resistance to PARP inhibitors (PARPis) is a clinical hurdle, and it is poorly understood how cancer cells escape the deadly effects of PARPis without restoring BRCA1/2 function. By synergizing the advantages of next-generation sequencing with functional genetic screens in tractable model systems, novel mechanisms providing useful insights into DNA damage response (DDR) have been identified. BRCA1/2 models not only are tools to explore therapy escape mechanisms but also yield basic knowledge about DDR pathways and PARPis’ mechanism of action. Moreover, alterations that render cells resistant to targeted therapies may cause new synthetic dependencies that can be exploited to combat resistant disease.","PeriodicalId":54233,"journal":{"name":"Annual Review of Cancer Biology-Series","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2019-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1146/ANNUREV-CANCERBIO-030617-050232","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47491059","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: 47
Functional Genomics for Cancer Research: Applications In Vivo and In Vitro 癌症研究的功能基因组学：体内外应用
IF 7.7 2区 医学
Annual Review of Cancer Biology-Series Pub Date : 2019-03-04 DOI: 10.1146/ANNUREV-CANCERBIO-030518-055742
T. O’Loughlin, Luke A. Gilbert
{"title":"Functional Genomics for Cancer Research: Applications In Vivo and In Vitro","authors":"T. O’Loughlin, Luke A. Gilbert","doi":"10.1146/ANNUREV-CANCERBIO-030518-055742","DOIUrl":"https://doi.org/10.1146/ANNUREV-CANCERBIO-030518-055742","url":null,"abstract":"Functional genomics holds great promise for the dissection of cancer biology. The elucidation of genetic cooperation and molecular details that govern oncogenesis, metastasis, and response to therapy is made possible by robust technologies for perturbing gene function coupled to quantitative analysis of cancer phenotypes resulting from genetic or epigenetic perturbations. Multiplexed genetic perturbations enable the dissection of cooperative genetic lesions as well as the identification of synthetic lethal gene pairs that hold particular promise for constructing innovative cancer therapies. Lastly, functional genomics strategies enable the highly multiplexed in vivo analysis of genes that govern tumorigenesis as well as of the complex multicellular biology of a tumor, such as immune response and metastasis phenotypes. In this review, we discuss both historical and emerging functional genomics approaches and their impact on the cancer research landscape.","PeriodicalId":54233,"journal":{"name":"Annual Review of Cancer Biology-Series","volume":"38 12","pages":""},"PeriodicalIF":7.7,"publicationDate":"2019-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1146/ANNUREV-CANCERBIO-030518-055742","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41283893","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: 9
Deciphering Human Tumor Biology by Single-Cell Expression Profiling 通过单细胞表达谱解读人类肿瘤生物学
IF 7.7 2区 医学
Annual Review of Cancer Biology-Series Pub Date : 2019-03-04 DOI: 10.1146/ANNUREV-CANCERBIO-030518-055609
I. Tirosh, M. Suvà
{"title":"Deciphering Human Tumor Biology by Single-Cell Expression Profiling","authors":"I. Tirosh, M. Suvà","doi":"10.1146/ANNUREV-CANCERBIO-030518-055609","DOIUrl":"https://doi.org/10.1146/ANNUREV-CANCERBIO-030518-055609","url":null,"abstract":"Human tumors are complex ecosystems where diverse cancer and noncancer cells interact to determine tumor biology and response to therapies. Genomic and transcriptomic methods have traditionally profiled these intricate ecosystems as bulk samples, thereby masking individual cellular programs and the variability among them. Recent advances in single-cell profiling have paved the way for studying tumors at the resolution of individual cells, providing a compelling strategy to bridge gaps in our understanding of human tumors. Here, we review methodologies for single-cell expression profiling of tumors and the initial studies deploying them in clinical contexts. We highlight how these studies uncover new biology and provide insights into drug resistance, stem cell programs, metastasis, and tumor classifications. We also discuss areas of technology development in single-cell genomics that provide new tools to address key questions in cancer biology. These emerging studies and technologies have the potential to revolutionize our understanding and management of human malignancies.","PeriodicalId":54233,"journal":{"name":"Annual Review of Cancer Biology-Series","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2019-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1146/ANNUREV-CANCERBIO-030518-055609","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46453120","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: 38
NAD+ Metabolism in Aging and Cancer 衰老与癌症中的NAD+代谢
IF 7.7 2区 医学
Annual Review of Cancer Biology-Series Pub Date : 2019-03-04 DOI: 10.1146/ANNUREV-CANCERBIO-030518-055905
T. Demarest, M. Babbar, M. Okur, Xiuli Dan, D. Croteau, Nima B Fakouri, M. Mattson, V. Bohr
{"title":"NAD+ Metabolism in Aging and Cancer","authors":"T. Demarest, M. Babbar, M. Okur, Xiuli Dan, D. Croteau, Nima B Fakouri, M. Mattson, V. Bohr","doi":"10.1146/ANNUREV-CANCERBIO-030518-055905","DOIUrl":"https://doi.org/10.1146/ANNUREV-CANCERBIO-030518-055905","url":null,"abstract":"Aging is a major risk factor for many types of cancer, and the molecular mechanisms implicated in aging, progeria syndromes, and cancer pathogenesis display considerable similarities. Maintaining redox homeostasis, efficient signal transduction, and mitochondrial metabolism is essential for genome integrity and for preventing progression to cellular senescence or tumorigenesis. NAD+ is a central signaling molecule involved in these and other cellular processes implicated in age-related diseases and cancer. Growing evidence implicates NAD+ decline as a major feature of accelerated aging progeria syndromes and normal aging. Administration of NAD+ precursors such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) offer promising therapeutic strategies to improve health, progeria comorbidities, and cancer therapies. This review summarizes insights from the study of aging and progeria syndromes and discusses the implications and therapeutic potential of the underlying molecular mechanisms involved in aging and how they may contribute to tumorigenesis.","PeriodicalId":54233,"journal":{"name":"Annual Review of Cancer Biology-Series","volume":" ","pages":""},"PeriodicalIF":7.7,"publicationDate":"2019-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1146/ANNUREV-CANCERBIO-030518-055905","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44684055","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: 41
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