[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-329878-105":59,"doc-detail-329878-en":123},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":116,"head_meta":118,"extra_data":120,"updated_unix":122},105,"en","the-metastatic-cascade-through-the-lens-of-therapeutic-inhibition-review","The metastatic cascade through the lens of therapeutic inhibition - Review","","Metastasis drives most cancer-related mortality, and mapping the metastatic cascade reveals intervention points where therapies can reduce progression or toxicity. This review examines vulnerabilities across multiple stages—from angiogenesis through secondary tumor formation—and explains how targeted inhibition may halt the cascade. It emphasizes mechanistic rationale, highlights therapeutic efficacy across multiple cancers, and identifies metastatic-cascade targets requiring further research to advance toward durable metastatic cancer remission.",{"@graph":69,"@context":115},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/the-metastatic-cascade-through-the-lens-of-therapeutic-inhibition-review/329878/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/the-metastatic-cascade-through-the-lens-of-therapeutic-inhibition-review/329878.png","ImageObject",300,407,{"name":92,"@type":93},"Valentina","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-23","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109],{"name":110,"@type":111,"acceptedAnswer":112},"How is angiogenesis connected to metastatic growth?","Question",{"text":113,"@type":114},"Solid tumors rely on aberrant angiogenesis to support rapid growth, and hypoxic tumor conditions activate signaling that upregulates VEGF and VEGF receptors.","Answer","https://schema.org",{"og:url":83,"og:type":117,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":119,"canonical":83},"index,follow",{"doc_id":121,"site_id":62},329878,1790401951,{"code":4,"msg":5,"data":124},{"doc_id":121,"user_id":125,"nickname":92,"user_avatar":126,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":127,"file_id":128,"file_url":129,"file_type":130,"file_size":131,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":132,"language":133,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":134,"faqs":135,"seo_title":136,"seo_description":67,"update_tm":137,"read_time":138},13056703020460,"https://ap-avatar.wpscdn.com/avatar/be000253dac470eee5d?_k=1778207105932848923","ll  \nOPEN ACCESS  \nReview  \nThe metastatic cascade through the lens of therapeutic inhibition  \nIan Miranda,1,2 Nusrat Jahan,3 and Lalita A. Shevde2,4,*  \n1Medical Scientist Training Program, University of Alabama at Birmingham, Birmingham, AL, USA  \n2Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA  \n3Division of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, AL, USA  \n4O’Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA  \n*Correspondence: [lsamant@uab.edu](lsamant@uab.edu)  \n[https://doi.org/10.1016/j.xcrm.2024.101872](https://doi.org/10.1016/j.xcrm.2024.101872)  \nSUMMARY  \nMetastasis is a main cause of cancer-related death, and a deeper understanding of the metastatic process will inform more targeted and mechanistic approaches that can abrogate challenges in treatment efficacyand toxicity. Several steps throughout the metastatic cascade, from angiogenesis to secondary tumor formation, offer specific vulnerabilities to therapies that can lead to the decline or cessation of metastatic progression. A deeper understanding of the metastatic cascade also allows combination systemic therapies to be used synergistically. In this review, we describe current treatment modalities in the context of multiple steps of the metastatic cascade. We highlight their mechanisms and present their efficacy across multiple cancers. This work also presents targets within the metastatic cascade in need of more research that can advance the landscape of treatments and lead to the goal of metastatic cancer remission.  \nINTRODUCTION  \nCancer remains a leading cause of death in the United States (US) and globally, with 9.7 million dying from the disease in 2022.1 In 2024, 611,720 cancer deaths are projected to occur in the US, alone.2 Metastasis, the spreading of cancer cells from the primary organ of origin to another part of the body, is a major cause for cancer-related death. While modern systemic treatment and occasional locoregional treatment have made metastatic cancer more clinically manageable over the last few decades, a long-lasting remission of metastasis remains an elusive goal. A deeper understanding of the metastatic cascade will offer additional targets for therapy that have the potential to yield more favorable outcomes than current treatments.3 ,4  \nMetastasis is the culmination of detachment of cancer cells from the primary tumor and the subsequent growth of those cells in a distant organ. This complex process of coordination and dynamic adaptation on the part of the cancer cells is enabled by significant remodeling of the primary and metastatic tumor microenvironments (TMEs) .5 The metastatic cascade is highly and inherently inefficient, with an overwhelming majority of cells dying before completing the process.6 ,7 The cells that do survive one of the steps, however, can either remain dormant or progress further through the cascade. Though a relatively small percentage of cells manage to advance, those that do are considered disseminated tumor cells (DTCs) and can lead to metastatic disease progression and adverse oncological outcomes.8  \nEach step of the cascade has vulnerabilities that can prohibit advancement to the next step (Figure 1) .9 Some of these vulner-  \nabilities have been leveraged as treatment targets, others have yet to be explored, and still others have only been identified atthe preclinical level. While clinically evident metastasis is often identified after the diagnosis of a primary tumor, for most patients, metastasis has already been initiated at the time of initial diagnosis.4 , 10 Currently, systemic therapy is the primary modality of metastatic disease, but this is accompanied by a range of toxicities that can lead to significant treatment-associated morbidities.11 Treatment-related adverse events are diverse and extremely relevant when considering improvements to cancer outcomes.12 Identifying targeted therapies tha","cbCaitGF9kmhUk3k","https://ap.wps.com/l/cbCaitGF9kmhUk3k","pdf",4486328,14,"English","# Summary\n# Introduction\n## Metastasis and the metastatic cascade\n# Angiogenesis","[{\"question\":\"How is angiogenesis connected to metastatic growth?\",\"answer\":\"Solid tumors rely on aberrant angiogenesis to support rapid growth, and hypoxic tumor conditions activate signaling that upregulates VEGF and VEGF receptors.\"}]","The metastatic cascade through the lens of therapeutic inhibition - Review | PDF",1789985973,35]