[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-405816-105":59,"doc-detail-405816-en":130},{"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":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","arising-novel-agents-in-lung-cancer-are-bispecics-and-adcs-the-new-paradigm","Arising Novel Agents in Lung Cancer: Are Bispecifics and ADCs the New Paradigm?","","Lung cancer remains the leading cause of cancer-related death worldwide, with non-small cell lung cancer (NSCLC) accounting for roughly 85% of diagnoses. Over the past two decades, immunotherapy and targeted therapy against driver mutations have improved outcomes, yet cancer cells frequently develop resistance, creating a need for effective next-generation options. This review highlights bispecific antibodies and antibody–drug conjugates as innovative modalities, assessing their promise for overcoming treatment resistance and improving anti-tumor targeting.",{"@graph":69,"@context":122},[70,84,105],{"@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/arising-novel-agents-in-lung-cancer-are-bispecics-and-adcs-the-new-paradigm/405816/",{"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/arising-novel-agents-in-lung-cancer-are-bispecics-and-adcs-the-new-paradigm/405816.png","ImageObject",300,407,{"name":92,"@type":93},"Kyle","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-31","2026-09-28",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why is NSCLC treatment resistant over time?","Question",{"text":112,"@type":113},"Even after immunotherapy and targeted therapy improve outcomes, cancer cells commonly acquire resistance through target-dependent changes or target-independent pathway bypass signaling.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What innovative agents does the review focus on?",{"text":117,"@type":113},"The review discusses bispecific antibodies and antibody–drug conjugates, emphasizing their ability to target tumor cells more effectively and potentially address resistance mechanisms.",{"name":119,"@type":110,"acceptedAnswer":120},"How have NSCLC therapies changed since the early 2000s?",{"text":121,"@type":113},"After the discovery of immune checkpoint inhibitors and driver mutations, treatment options expanded rapidly, including PD-L1–based immunotherapies and targeted tyrosine kinase inhibitor regimens.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},405816,1790804328,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},3985741905716,"https://ap-avatar.wpscdn.com/davatar_994ba38a5ba835b3df7d355c54d3ed8d","cancers   \nReview  \nArising Novel Agents in Lung Cancer: Are Bispecifics and ADCs the New Paradigm?  \nAmanda Reyes, Rebecca Pharaon, Atish Mohanty  and Erminia Massarelli *  \nCitation: Reyes, A.; Pharaon, R.; Mohanty, A.; Massarelli, E. Arising Novel Agents in Lung Cancer: Are Bispecifics and ADCs the New Paradigm? Cancers 2023, 15, 3162 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)cancers15123162  \nAcademic Editor: Massimo Broggini  \nReceived: 18 May 2023  \nRevised: 5 June 2023  \nAccepted: 7 June 2023  \nPublished: 13 June 2023  \nCopyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \nDepartment of Medical Oncology & Therapeutics Research, City of Hope National Medical Center,  \nDuarte, CA 910102, USA; [amareyes@coh.org](amareyes@coh.org) (A.R.); [rpharaon@coh.org](rpharaon@coh.org) (R.P.); [amohanty@coh.org](amohanty@coh.org) (A.M.)  \n* Correspondence: [emassarelli@coh.org](emassarelli@coh.org)  \nSimple Summary: Lung cancer is the leading cause of cancer-related death worldwide according to the World Health Organization. Non-small cell lung cancer makes up the majority of cases. Immunotherapy with immune checkpoint inhibitors and targeted therapy with tyrosine kinase inhibitors and other molecular targeted agents significantly changed the treatment landscape and overall survival. Unfortunately, resistance to these treatments develops, and there is a need to identify additional innovative therapies that can overcome treatment resistance. Advancements in biomedical engineering and technology allowed for the development of novel agents, capable of delivering effective treatment directly to tumor cells. These agents include antibody drug conjugatesand bispecific antibodies which have various targets and mechanisms of action, discussed in depth in this review.  \nAbstract: Lung cancer is one of the most common cancers with the highest mortality. Non-small cell lung cancer (NSCLC) contributes to around 85% of lung cancer diagnoses (vs. 15% for small cell lung cancer) . The treatment of NSCLC has vastly changed in the last two decades since the development of immunotherapy and targeted therapy against driver mutations. As is the nature of malignancy, cancer cells have acquired resistance to these treatments prompting an investigation into novel treatments and new targets. Bispecific antibodies, capable of targeting multiple substrates at once, and antibody–drug conjugates that can preferentially deliver chemotherapy to tumor cells are examples of this innovation. From our initial evaluation, both treatment modalities appear promising.  \nKeywords: non-small cell lung cancer; EGFR mutated; immunotherapy; targeted therapy; bispecific antibodies; antibody-drug conjugates; EGFR resistance; MET amplification; Axl signaling; HER2; HER3; cMet signaling  \n1. Introduction  \nLung cancer is the leading cause of cancer-related death worldwide according to the WHO [1] . Non-small cell lung cancer (NSCLC) contributes to around 85% of lung cancer diagnoses (vs. 15% for small cell lung cancer), which is further categorized into adenocarcinoma 78% and squamous 18%[2] . Since the early 2000s, the treatment options for NSCLC have exponentially increased after the discovery of immune checkpoint inhibitors and targetable `driver mutations' [2,3] . Immune checkpoint inhibitors, pembrolizumab, atezolizumab, and cemiplimab were proven effective first-line agents in programmed cell death ligand 1 [PD-L1] positive metastatic NSCLC after the respective phase 3 trials [4–6] . Combination PD-L1 and cytotoxic T-lymphocyte-associated protein 4 [CTLA-4] inhibitors, nivolumab and ipilimumab were also proven in the first line compared to sta","cbCaioc8a980hgMv","https://ap.wps.com/l/cbCaioc8a980hgMv","pdf",835440,13,"English","# 1. Introduction\n# 2. Bispecific Antibodies","[{\"question\":\"Why is NSCLC treatment resistant over time?\",\"answer\":\"Even after immunotherapy and targeted therapy improve outcomes, cancer cells commonly acquire resistance through target-dependent changes or target-independent pathway bypass signaling.\"},{\"question\":\"What innovative agents does the review focus on?\",\"answer\":\"The review discusses bispecific antibodies and antibody–drug conjugates, emphasizing their ability to target tumor cells more effectively and potentially address resistance mechanisms.\"},{\"question\":\"How have NSCLC therapies changed since the early 2000s?\",\"answer\":\"After the discovery of immune checkpoint inhibitors and driver mutations, treatment options expanded rapidly, including PD-L1–based immunotherapies and targeted tyrosine kinase inhibitor regimens.\"}]","Arising Novel Agents in Lung Cancer: Are Bispecifics and ADCs the New Paradigm? | PDF",1790561946,33]