Antibody drug conjugates in non-small cell lung cancer: An emerging therapeutic approach. (January 2022)

• Record Type: Journal Article
• Authors: Marks, S; Naidoo, J
• Is Part Of: Lung cancer. Volume 163(2022)
• Page Start: 59
• Page End: 68
• Publication Date: 2022-01
• Subjects: ADC Antibody drug conjugates -- ADCC Antibody-dependent cell-mediated cytotoxicity -- ADCP Antibody-dependent cell-mediated phagocytosis -- ALK Anaplastic lymphoma kinase -- AMT Aminomethytransferase -- APC Antigen-presenting cells -- ATE Antibody-triggered endocytosis -- AXL AXL tyrosine receptor kinase -- BRAF V-raf murine sarcoma viral oncogene homolog B1 -- bsADC Bispecific antibody drug conjugate -- C1q Completment component 1q -- C797S Cysteine substitution to Serine at codon 797 (exon 19 EGFR gene) -- CAB Conditionally active biologic -- CD Cluster of differentiation -- CDK4/6 Cyclin-dependent kinase(s) 4/6 -- CEA Carcinoembryonic antigen -- EACAM5 CEA cell adhesion molecule 5 -- c-MET Tyrosine-protein kinase Met (Hepatocyte growth factor receptor HGFR) -- CTLA-4 Cytotoxic T-lymphocyte-associated protein 4 -- DAR Drug-antibody ratio -- DCR Disease control rate -- DLL3 Delta-like 3 protein -- DM1 Emtansine -- DM4 Ravtansine -- DOR Duration of response -- DS-8201 Trastuzumab-deruxtecan -- EGFR Epithelial growth factor receptor -- EpCAM Epithelial cell adhesion molecule -- EML4-ALK Echinoderm microtubule-associated protein-like 4 with ALK (fusion protein) -- ERBB2 Erb-B2 Receptor Tyrosine Kinase 2 -- ESMO European Society of Medical Oncology -- FDA U.S. Food and Drug Administration -- FRα Folate receptor alpha -- FOXO3α Forkhead box O3α -- HER2 Human epidermal growth factor receptor 2 -- HER3 Human epidermal growth factor receptor 3 -- HER3-DXd Patritumab-deruxtecan -- ICI Immune checkpoint inhibito -- IHC Immunohistochemistry -- ILD Interstitial lung disease -- ISAC mmune stimulatory drug conjugate -- L858R Leucine substitution to Arginine at position 858 (exon 21 EGFR gene) -- LIFR Leukaemia inhibitory factor receptor -- 177Lu Lutetium-177 (isotope) -- Ly6E Lymphocyte antigen 6 family member E -- mAb Monoclonal antibody -- MAPK Mitogen-activated protein kinase -- MC Maleimidoca-propyl (linker) -- MCC Maleimidomethyl cyclohexane-1-carboxylate (linker) -- MET MET proto-oncogene receptor tyrosine kinase -- MMAE Monomethyl auristatin E -- MMAF Monomethyl auristatin F -- MT1-MMP/MMP14 Membrane type 1 matrix metalloproteinase -- MUC4 Mucin 4 cell surface associated protein coding gene -- 277Th Thorium-277 (sotope) -- mTOR Mammalian target of rapamycin protein -- NaPi2b Sodium-dependent phosphate transport protein 2B -- NCCN National Comprehensive Cancer Network -- NE Not evaluable -- NGS Next generation sequencing -- NSCLC Non-small cell lung cancer -- NTRK Neurotrophic Tyrosine Kinase (fusion) -- ORR Overall response rate -- P-gp-MDR1 P-glycoprotein 1 (Multi-drug resistant) -- p95HER2 p95 truncated HER2 receptor -- PD1 Programmed cell death protein 1 -- PD-L1 Programmed death ligand 1 -- PFS Progression free survival -- PI3K Phosphoinositide 3-kinase -- PLK1 Serine/threonine-protein kinase 1 (Polo-like kinase 1) -- PTK7 Tyrosine-protein kinase-like 7 (Colon carcinoma kinase 4) -- PVRL4 Poliovirus-receptor-like 4 (Nectin4) -- Raf Rapidly accelerated fibrosarcoma (gene) -- Ras Rat sarcoma virus (gene) -- RET 'Rearrangement during transfection' proto-oncogene receptor tyrosine kinase -- RIC Radioimmunoconjugate -- ROS c-ros oncogene (rearrangement) -- Rova-T Rovalpituzumab-tesirine -- RTK Receptor tyrosine kinase -- SAR408701 Tusamitamab-Ravtansine -- SLC46A3 Solute carrier family 46 member 3 (protein) -- STAT3 Signal transducer and activator of transcription 3 -- T790M Threonine substitution to methionine at position 790 (exon 20EGFR gene) -- T-DM1 Trastuzumab-emtansine -- TKI Tyrosine kinase inhibitor -- TLR Toll-like receptor -- TME Tumour microenvironment -- TROP2 Tumour-associated calcium signal transducer 2 (gene) -- TUBB3 Tubulin Beta 3 Class 3 (protein) -- U3-1402 Patritumab-deruxteca -- VEGF2 Vascular endothelial growth factor 2; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2021.11.016
• Languages: English
• ISSNs: 0169-5002

Abstract

Abstract: The current standard-of-care for the treatment of advanced non-small cell lung cancer (NSCLC) incorporates targeted therapies, immune-checkpoint inhibitors (ICI) and systemic chemotherapy. Antibody-drug conjugates (ADC) are a class of anti-cancer therapy capable of transporting cytotoxic drugs directly to tumour cells, thus harnessing the strengths of both cytotoxic chemotherapy and targeted therapy. In this review we provide a comprehensive review the design, mode of action, and mechanisms of resistance to ADCs in NSCLC. We also summarize the clinical development of several promising ADCs in early phase clinical trials for the treatment NSCLC. including ADCs against well-established targets (e.g.HER2 in breast cancer, Nectin4 in urothelial cancer), novel antigenic targets (e.g. HER3, TROP2, PTK7, CEACAM5), as well as promising combinations with agents known to be active in NSCLC such as tyrosine kinase inhibitors and ICI therapy, as a strategy to overcome mechanisms of resistance to ADC therapy.