Biomarkers of drugs targeting HER‐family signalling in cancer

Abstract

The epidermal growth factor receptor family (EGFR/HER) is frequently deregulated in human cancers. Several aberrations at various levels have been successfully exploited as targets for anti-cancer therapies. However, with very few exceptions, drugs targeting HER signalling have shown only modest activity when used alone in cancers where a HER-related target can be identified. Optimization of the use of these drugs either alone or in combination with other anti-cancer agents would require a more precise definition of alterations that could predict for activity or resistance. Clinical validation of the several potential biomarkers emerging from clinical and translational studies is a challenging process. Thanks to combined efforts, collection of tumour tissues and other potentially relevant patients' materials has become more and more frequently mandatory in prospective studies with biologically targeted therapies. As a consequence, information on the value of promising biomarkers of drugs targeting HER-family receptor targeting is becoming available. This review will focus on breast cancer, where the HER2 subset has been the subject of a major research effort in the last two decades, and on gastric cancer, where HER2 targeting has emerged recently as a successful strategy.

Overcoming resistance to HER2-targeted therapy with a novel HER2/CD3 bispecific antibody

“…However, HER2 expression does not guarantee a clinical response to trastuzumab or other HER2-targeted therapies 2,3 . HER2-positive breast cancer patients with metastatic disease initially respond to trastuzumab and/or other HER2-targeted therapies, but almost all eventually will develop resistance and relapse 4 . In osteosarcoma and Ewing's sarcoma, where high levels of HER2 expression was associated with decreased survival, 5 trastuzumab has not shown any benefit even when used in conjunction with cytotoxic chemotherapy 6 .…”

A Meta-Analysis on the Relations between EGFR R521K Polymorphism and Risk of Cancer

“…Abnormal expression or activity of EGFR observed in many types of cancer, like breast cancer, colorectal cancer, non-small-cell lung cancer, head and neck squamous cell carcinoma, has been considered as an important marker in tumorigenesis, which resulted in more aggressive tumor phenotype, higher recurrence rate, and poorer prognosis [1–4]. …”

Biomarkers in Lung Adenocarcinoma: A Decade of Progress

“…Therapeutic targeting of this event in breast carcinoma, in particular, has had a significant positive impact on clinical outcomes. 127 The best-defined mechanism of ERBB2 activation in lung ACA is in the form of small exon 20 in-frame insertion mutations occurring at or around codon 775 and leading to duplications of some or all of the YVMA amino acid sequence. 128 Copy number changes have not been a component of regular mutation screening in lung ACA; however, selected studies suggest that ERBB2 amplification is a relatively infrequent event in this tumor type but appears to correlate with the presence of an ERBB2-activating mutation.…”