Mechanisms of lapatinib resistance in HER2-driven breast cancer.
Targeted therapies have been approved for various malignancies but the acquisition of resistance remains a substantial challenge in the clinical management of advanced cancers. Twenty-five per cent of breast cancers overexpress ErbB2/HER2, which confers a more aggressive phenotype and is associated with a poor prognosis. HER2-targeting therapies (trastuzumab, pertuzumab, TDM1 and lapatinib) are available, but a significant fraction of HER2-positive breast cancers eventually relapse or progress. This suggests that acquired or intrinsic resistance enables escape from HER2 inhibition. This review focuses on mechanisms of intrinsic/acquired resistance to lapatinib identified in preclinical and clinical studies. A better understanding of these mechanisms could lead to novel predictive markers of lapatinib response and to novel therapeutic strategies for breast cancer patients.
Dipartimento di Medicina Clinica e Chirurgia, Università di Napoli Federico II, 80131 Naples, Italy.
Valentina
V
D'Amato
Dipartimento di Medicina Clinica e Chirurgia, Università di Napoli Federico II, 80131 Naples, Italy.
Lucia
L
Raimondo
Dipartimento di Medicina Clinica e Chirurgia, Università di Napoli Federico II, 80131 Naples, Italy.
Luigi
L
Formisano
Dipartimento di Medicina Clinica e Chirurgia, Università di Napoli Federico II, 80131 Naples, Italy.
Mario
M
Giuliano
Dipartimento di Medicina Clinica e Chirurgia, Università di Napoli Federico II, 80131 Naples, Italy.
Sabino
S
De Placido
Dipartimento di Medicina Clinica e Chirurgia, Università di Napoli Federico II, 80131 Naples, Italy.
Roberta
R
Rosa
Dipartimento di Medicina Clinica e Chirurgia, Università di Napoli Federico II, 80131 Naples, Italy. Electronic address: robianco@unina.it.
Roberto
R
Bianco
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D005260:Female; D005784:Gene Amplification; D006801:Humans; D000077341:Lapatinib; D009154:Mutation; D010770:Phosphotransferases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011799:Quinazolines / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism
D000970:Antineoplastic Agents; D000077341:Lapatinib; D010770:Phosphotransferases; D011505:Protein-Tyrosine Kinases; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; C508053:ERBB2 protein, human
Breast cancer; ErbB2/HER2; Lapatinib; Resistance