Introduction Triple-negative breast cancer (TNBC) is a heterogeneous disease characterized by the lack of estrogen receptor (ER), progesterone receptor (PR), and epidermal growth factor receptor 2 (HER2) and often associated with poor survival outcomes. The backbone of current treatments for TNBC relies on chemotherapy; however, resistance to cytotoxic agents is a commonly encountered hurdle to overcome. Areas covered Current understanding on the mechanisms involved in TNBC chemoresistance is evaluated and novel potential actionable targets and recently explored modalities for carrying and delivering chemotherapeutics are highlighted. Expert opinion A comprehensive identification of both genomic and functional TNBC signatures is required for a more definite categorization of the patients in order to prevent insensitivity to chemotherapy and therefore realize the full potential of precision-medicine approaches. In this scenario, cell-line-derived xenografts (CDX), patient-derived xenografts (PDX), patient-derived orthotopic xenografts (PDOX), and patient-derived organoids (PDO) are indispensable experimental models for evaluating the efficacy of drug candidates and predicting the therapeutic response. The combination of increasingly sensitive 'omics' technologies, computational algorithms, and innovative drug modalities may accelerate the successful translation of novel candidate TNBC targets from basic research to clinical settings, thus contributing to reach optimal clinical output, with lower side effects and reduced resistance.

Triple-negative breast cancer drug resistance, durable efficacy, and cure: how advanced biological insights and emerging drug modalities could transform progress

De Francesco, Ernestina Marianna;Vella, Veronica;Belfiore, Antonino;
2022

Abstract

Introduction Triple-negative breast cancer (TNBC) is a heterogeneous disease characterized by the lack of estrogen receptor (ER), progesterone receptor (PR), and epidermal growth factor receptor 2 (HER2) and often associated with poor survival outcomes. The backbone of current treatments for TNBC relies on chemotherapy; however, resistance to cytotoxic agents is a commonly encountered hurdle to overcome. Areas covered Current understanding on the mechanisms involved in TNBC chemoresistance is evaluated and novel potential actionable targets and recently explored modalities for carrying and delivering chemotherapeutics are highlighted. Expert opinion A comprehensive identification of both genomic and functional TNBC signatures is required for a more definite categorization of the patients in order to prevent insensitivity to chemotherapy and therefore realize the full potential of precision-medicine approaches. In this scenario, cell-line-derived xenografts (CDX), patient-derived xenografts (PDX), patient-derived orthotopic xenografts (PDOX), and patient-derived organoids (PDO) are indispensable experimental models for evaluating the efficacy of drug candidates and predicting the therapeutic response. The combination of increasingly sensitive 'omics' technologies, computational algorithms, and innovative drug modalities may accelerate the successful translation of novel candidate TNBC targets from basic research to clinical settings, thus contributing to reach optimal clinical output, with lower side effects and reduced resistance.
Triple-negative breast cancer (TNBC)
antibody-drug conjugates (ADCs)
chemoresistance
drug delivery strategies
nanoparticles
Drug Resistance
Humans
Precision Medicine
Receptors, Estrogen
Triple Negative Breast Neoplasms
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11769/541369
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