Antibody–drug conjugates for lung cancer in the era of personalized oncology. (February 2021)

• Record Type: Journal Article
• Authors: Ricciuti, Biagio; Lamberti, Giuseppe; Andrini, Elisa; Genova, Carlo; De Giglio, Andrea; Bianconi, Vanessa; Sahebkar, Amirhossein; Chiari, Rita; Pirro, Matteo
• Is Part Of: Seminars in cancer biology. Volume 69(2021)
• Page Start: 268
• Page End: 278
• Publication Date: 2021-02
• Subjects: AC adenocarcinoma -- ADC antibody-drug conjugate -- ADCC antibody-dependent cellular cytotoxicity -- AE adverse event -- AKT protein kinase B -- ALK anaplastic lymphoma kinase -- CDCC complement-dependent cytotoxicity -- c-MET mesenchymal epithelial transition -- DAR drug-to-antibody ratio -- DCR disease control rate -- DLL3 Delta-like 3 -- DLTs dose-limiting toxicities -- EGFR epidermal growth factor receptor -- ERK extracellular signal-regulated kinase -- FISH fluorescence in situ hybridization -- HER2 human epidermal grow factor receptor 2 -- IHC immunohistochemistry -- mAb monoclonal antibody -- MAPK mitogen activating protein kinase -- mDOR median duration of response -- MMAE microtubule inhibitor monomethyl auristatin E -- mOS median overall survival -- mPFS median progression-free survival -- NaPi2b type IIb sodium-dependent phosphate transporter -- NSCLC non-small cell lung cancer -- ORR objective response rate -- PDX patient-derived xenograft -- PI3K phosphatidylinositol-3-kinase -- PTK7 protein tyrosine kinase 7 -- RTK receptor tyrosine kinase -- SCLC small cell lung cancer -- SqCC squamous cell carcinoma -- TKI tyrosine kinase inhibitors -- Trop-2 trophoblast cell surface antigen 2; Antibody-Drug conjugate -- Cancer -- Nanomedicine -- NSCLC -- SCLC; Cancer -- Periodicals; Neoplasms -- Periodicals; Review Literature; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.semcancer.2019.12.024
• Languages: English
• ISSNs: 1044-579X

Abstract

Abstract: With 9.6 million deaths in 2018, cancer represents one of the most common causes of death, both in men and women. Despite recent advances in the understanding of molecular mechanisms involved in cancer development and progression, treatment options are still limited. Limitations of traditional chemotherapy include the lack of selectivity and the unfavorable safety profile. The efficacy of targeted therapies ( e.g., tyrosine kinase inhibitors) is also limited by their cytostatic action, which inhibits tumor cell proliferation without inducing tumor cell death, and by the risk of acquired resistance. Antibody-drug conjugates (ADCs), a newly developed class of engineered anticancer drugs, consist of recombinant monoclonal antibodies against tumor-specific antigens that are covalently bound to cytotoxic agents. They have been designed to overcome the limitations of traditional chemotherapy and targeted therapies by combining the target selectivity of monoclonal antibodies with the high potency of cytotoxic drugs. Currently, ADCs that have received regulatory approval include brentuximab vedotin for CD30-positive Hodgkin lymphoma and trastuzumab emtansine for human epidermal growth factor receptor 2-positive breast cancer. However, over 80 novel ADCs are actively being investigated in preclinical studies and early-phase clinical trials. In this review, we will provide a comprehensive overview of the biological rational, efficacy and safety of ADCs as therapeutic agents against non-small cell lung cancer and small cell lung cancer.