The target invites a foe: antibody-drug conjugates in gynecologic oncology.
Curr Opin Obstet Gynecol
; 30(1): 44-50, 2018 Feb.
Article
em En
| MEDLINE
| ID: mdl-29227302
ABSTRACT
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. A better and quicker translation of recent scientific advances in the field of ADCs into rational clinical trials for patients diagnosed with ovarian, endometrial or cervical cancer could create real improvements in tumor response, survival and quality of life for our patients.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Imunoconjugados
/
Terapia de Alvo Molecular
/
Antineoplásicos Imunológicos
/
Neoplasias dos Genitais Femininos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Female
/
Humans
País/Região como assunto:
America do norte
Idioma:
En
Revista:
Curr Opin Obstet Gynecol
Assunto da revista:
GINECOLOGIA
/
OBSTETRICIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos