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The target invites a foe: antibody–drug conjugates in gynecologic oncology

Purpose of review Antibody–drug conjugates (ADCs) represent a promising new class of cancer therapeutics. Currently more than 60 ADCs are in clinical development, however, only very few trials focus on gynecologic malignancies. In this review, we summarize the most recent advances in ADC drug development with an emphasis on how this progress relates to patients diagnosed with gynecologic malignancies and breast cancer. Recent findings The cytotoxic payloads of the majority of the ADCs that are currently in clinical trials for gynecologic malignancies or breast cancer are auristatins (MMAE, MMAF), maytansinoids (DM1, DM4), calicheamicin, pyrrolobenzodiazepines and SN-38. Both cleavable and noncleavable linkers are currently being investigated in clinical trials. A number of novel target antigens are currently being validated in ongoing clinical trials including folate receptor alpha, mesothelin, CA-125, NaPi2b, NOTCH3, protein tyrosine kinase-like 7, ephrin-A4, TROP2, CEACAM5, and LAMP1. For most ADCs currently in clinical development, dose-limiting toxicities appear to be unrelated to the targeted antigen but more tightly associated with the payload. Rational drug design involving optimization of the antibody, the linker and the conjugation chemistry is aimed at improving the therapeutic index of new ADCs. Summary Antibody–drug conjugates can increase the efficacy and decrease the toxicity of their payloads in comparison with traditional cyctotoxic agents....
Source: Current Opinion in Obstetrics and Gynecology - Category: OBGYN Tags: GYNECOLOGIC ONCOLOGY: Edited by Gottfried E. Konecny Source Type: research

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Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
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Source: Cancer Epidemiology Biomarkers and Prevention - Category: Cancer & Oncology Authors: Tags: Research Articles Source Type: research
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Source: The Lancet Oncology - Category: Cancer & Oncology Authors: Tags: News Source Type: research
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Source: Journal of Gynecologic Oncology - Category: OBGYN Tags: J Gynecol Oncol Source Type: research
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Source: Cancer Epidemiology - Category: Cancer & Oncology Source Type: research
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Source: Science - The Huffington Post - Category: Science Source Type: news
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Source: Cellular and Molecular Biology - Category: Molecular Biology Tags: Cell Mol Biol (Noisy-le-grand) Source Type: research
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Source: Cancer Epidemiology Biomarkers and Prevention - Category: Cancer & Oncology Authors: Tags: General Epidemiology and Biostatistics: Poster Presentations - Proffered Abstracts Source Type: research
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Source: American Cancer Society :: News and Features - Category: Cancer & Oncology Tags: Cancer Risks/Causes Source Type: news
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Source: Molecular Medicine Reports - Category: Molecular Biology Tags: Mol Med Rep Source Type: research
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