A role for the pseudokinase HER3 in the acquired resistance against EGFR- and HER2-directed targeted therapy

2014 ◽  
Vol 42 (4) ◽  
pp. 831-836 ◽  
Author(s):  
Jeroen Claus ◽  
Gargi Patel ◽  
Tony Ng ◽  
Peter J. Parker
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Therapeutic Strategy ◽  
Acquired Resistance ◽  
Growth Factor Receptor ◽  
Targeted Therapeutics ◽  
Epidermal Growth ◽  
Egfr Family ◽  
Receptor Family

Specific inhibition of members of the EGFR (epidermal growth factor receptor) family, particularly EGFR and HER2 (human epidermal growth factor receptor 2), are an important therapeutic strategy in many human cancers. Compared with classical chemotherapy, these targeted therapeutics are very specific and initially effective, but acquired resistance against these targeted therapies is a recurring threat. A growing body of recent work has highlighted a pseudokinase in the EGFR family, HER3, and its ligand, NRG (neuregulin β1), to be of importance in models of resistant cancers, as well as in patients. In the present article, we describe some of the roles in which HER3 can mediate acquired resistance and discuss the current efforts to target HER3 itself in cancer.

scholarly journals Differential effects of epidermal growth factor receptor inhibitors in a single patient with neuropathic pain

2021 ◽  
Vol 14 (3) ◽  
pp. e239385
Author(s):  
Marte Grønlie Cameron ◽  
Christian Kersten
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Neuropathic Pain ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Differential Effects ◽  
Pain Scores ◽  
Medical Need ◽  
Epidermal Growth ◽  
Egfr Family

Neuropathic pain (NP) represents an unmet medical need, where analgesic responses to different epidermal growth factor receptor inhibitors (EGFR-Is) have been described. The human EGFR family of receptors consists of four members (human epidermal growth factor receptor, HER 1–4), signalling via different homodimer and heterodimer combinations. A 52-year-old man was treated with the EGFR-I cetuximab in a trial of severe NP. Pain scores decreased dramatically after blinded cetuximab, but not after placebo. On pain recurrence after the trial, he was prescribed the oral EGFR-Is erlotinib, gefitinib, and lapatinib without relief. However, treatment with the pan-HER-inhibitor afatinib was effective. After 4 years on afatinib, pain control remains excellent with manageable side effects. This is the first reported observation of differential effects of EGFR-Is on NP in the same patient and the first report describing NP relief with afatinib. Further understanding of the underlying pathophysiology could lead to development of EGFR-Is specifically targeting NP.

Critical Update and Emerging Trends in Epidermal Growth Factor Receptor Targeting in Cancer

2005 ◽  
Vol 23 (11) ◽  
pp. 2445-2459 ◽  
Author(s):  
José Baselga ◽  
Carlos L. Arteaga
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Egfr Gene ◽  
Epidermal Growth ◽  
Egfr Tkis ◽  
Receptor Family

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase of the ErbB receptor family that is abnormally activated in many epithelial tumors. The aberrant activation of the EGFR leads to enhanced proliferation and other tumor-promoting activities, which provide a strong rationale to target this receptor family. There are two classes of anti-EGFR agents: monoclonal antibodies (MAbs) directed at the extracellular domain of the receptor and small molecule, adenosine triphosphate–competitive inhibitors of the receptor's tyrosine kinase. Anti-EGFR MAbs have shown antitumor activity in advanced colorectal carcinoma, squamous cell carcinomas of the head and neck, non–small-cell lung cancer (NSCLC) and renal cell carcinomas. The tyrosine kinase inhibitors (TKIs) have a partially different activity profile. They are active against NSCLC, and a specific EGFR inhibitor has shown improvement in survival. Recently, mutations and amplifications of the EGFR gene have been identified in NSCLC and predict for enhanced sensitivity to anti-EGFR TKIs. In addition to specific anti-EGFR TKIs, there are broader acting inhibitors such as dual EGFR HER-2 inhibitors and combined anti-pan-ErbB and antivascular endothelial growth factor receptor inhibitors. Current research efforts are directed at selecting the optimal dose and schedule and identifying predictive factors of response and resistance beyond EGFR gene mutations and/or amplifications. Finally, there is a need for improved strategies to integrate anti-EGFR agents with conventional therapies and to explore combinations with other molecular targeted approaches including other antireceptor therapies, receptor-downstream signaling transduction inhibitors, and targeted approaches interfering with other essential drivers of cancer, such as angiogenesis.

Sign in / Sign up

Export Citation Format

Share Document