HER3/ErbB3, an emerging cancer therapeutic target

Zhang, Ningyan; Chang, Yujun; Rios, Adan; An, Zhiqiang

doi:10.1093/abbs/gmv103

Cited by 70 publications

(63 citation statements)

References 94 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Anti-HER2 antibodies such as Herceptin develop acquired resistance through a variety of mechanisms, including activation of tyrosine kinase in CSCs, upregulation of HER3, activating mutations in the p110a subunit of PIKK (PIK3CA), enhanced HER-ligand autocrine signaling and alterations in apoptotic pathways [69]. HER3 has now also been proposed as potentially driving survival of HER2+ cells once they have developed resistance to HER2 inhibitors such as lapatinib and trastuzumab [69].…”

Section: Use Of Multiple Mechanismsmentioning

confidence: 99%

Molecular chess? Hallmarks of anti-cancer drug resistance

2017

View full text Add to dashboard Cite

BackgroundThe development of resistance is a problem shared by both classical chemotherapy and targeted therapy. Patients may respond well at first, but relapse is inevitable for many cancer patients, despite many improvements in drugs and their use over the last 40 years.ReviewResistance to anti-cancer drugs can be acquired by several mechanisms within neoplastic cells, defined as (1) alteration of drug targets, (2) expression of drug pumps, (3) expression of detoxification mechanisms, (4) reduced susceptibility to apoptosis, (5) increased ability to repair DNA damage, and (6) altered proliferation. It is clear, however, that changes in stroma and tumour microenvironment, and local immunity can also contribute to the development of resistance. Cancer cells can and do use several of these mechanisms at one time, and there is considerable heterogeneity between tumours, necessitating an individualised approach to cancer treatment. As tumours are heterogeneous, positive selection of a drug-resistant population could help drive resistance, although acquired resistance cannot simply be viewed as overgrowth of a resistant cancer cell population. The development of such resistance mechanisms can be predicted from pre-existing genomic and proteomic profiles, and there are increasingly sophisticated methods to measure and then tackle these mechanisms in patients.ConclusionThe oncologist is now required to be at least one step ahead of the cancer, a process that can be likened to ‘molecular chess’. Thus, as well as an increasing role for predictive biomarkers to clinically stratify patients, it is becoming clear that personalised strategies are required to obtain best results.

show abstract

Section: Use Of Multiple Mechanismsmentioning

confidence: 99%

Molecular chess? Hallmarks of anti-cancer drug resistance

2017

View full text Add to dashboard Cite

show abstract

“…Sequencing of all coding exons of ERBB3 identified specific somatic mutations in ERBB3, and expression of the ERBB3 mutants in breast epithelial cells led to oncogenic transformation in the presence of HER2 (129). Several investigational drugs at various stages of development have been described for ERBB3 (130), and whether the more recently identified ERBB3 mutations are sensitive to ERBB3 and/or HER2 targeted therapies remain to be addressed.…”

Section: 2 Her/erbb Familymentioning

confidence: 99%

The role of HER2, EGFR, and other receptor tyrosine kinases in breast cancer

Hsu

Hung

2016

Cancer Metastasis Rev

294

185

View full text Add to dashboard Cite

Breast cancer affects approximately 1 in 8 women, and it is estimated that over 246,660 women in the United States will be diagnosed with breast cancer in 2016. Breast cancer mortality has decline over the last two decades due to early detection and improved treatment. Over the last few years, there is mounting evidence to demonstrate the prominent role of receptor tyrosine kinases (RTKs) in tumor initiation and progression, and targeted therapies against the RTKs have been developed, evaluated in clinical trials, and approved for many cancer types, including breast cancer. However, not all breast cancers are the same as evidenced by the multiple subtypes of the disease, with some more aggressive than others, showing differential treatment response to different types of drugs. Moreover, in addition to canonical signaling from the cell surface, many RTKs can be trafficked to various subcellular compartments, such as the multivesicular body and nucleus, where they carry out critical cellular functions, such as cell proliferation, DNA replication and repair, and therapeutic resistance. In this review, we provide a brief summary on the role of a selected number of RTKs in breast cancer and describe some mechanisms of resistance.

show abstract

“…Among four members of the HER family (EGFR, HER2, HER3 and HER4), HER3 is indicated to play an important role in HER signaling and drug resistance (19). With dimerization with EGFR or HER2, HER3 signals through phosphatidylinositol 3-kinase pathway (20,21).…”

Section: Introductionmentioning

confidence: 99%

Prognostic relevance of FGFR2 expression in stageï¿½II/III gastric cancer with curative resection and S‑1 chemotherapy

et al. 2017

View full text Add to dashboard Cite

Abstract. Curative gastrectomy and adjuvant chemotherapy using S-1 is a standard treatment for stage II/III gastric cancer in Japan. The purpose of the present study was to evaluate the prognostic relevance of fibroblast growth factor receptor (FGFR)2 expression in patients with stage II/III gastric cancer that underwent postoperative adjuvant chemotherapy with S-1. Formalin-fixed paraffin-embedded surgical specimens were retrospectively examined in 167 patients with stage II/III gastric cancer that underwent curative gastrectomy followed by adjuvant S1 chemotherapy. FGFR2 expression was measured using immunohistochemistry (IHC) staining. The IHC results for FGFR2 were as follows: Grade 1+, 32; grade 2+, 80; grade 3+, 55 patients. The FGFR2 expression level was not significantly associated with relapse-free or overall survival rates. However, in the diffuse type, the FGFR2 expression level tended to be negatively correlated with relapse-free survival. In particular, the proportion of patients who recurred >5 years following surgery was significantly larger in the FGFR2 grade 3+ group than in the grade 1+, 2+ group (4/22 vs. 1/35; P=0.047). The recurrent sites of long-term failure were mostly peritoneum among the diffuse type. To the best of our knowledge, the present study indicated for the first time that FGFR2 could predict long-term failure of adjuvant S-1 chemotherapy in curative advanced gastric cancer. There was no interaction between FGFR2 expression and patient survival outcomes in stage II/III gastric cancer. Patients with FGFR2 3+ in stage II/III gastric cancer should carefully be followed-up for >5 years after surgery.

show abstract

HER3/ErbB3, an emerging cancer therapeutic target

Cited by 70 publications

References 94 publications

Molecular chess? Hallmarks of anti-cancer drug resistance

Molecular chess? Hallmarks of anti-cancer drug resistance

The role of HER2, EGFR, and other receptor tyrosine kinases in breast cancer

Prognostic relevance of FGFR2 expression in stageï¿½II/III gastric cancer with curative resection and S‑1 chemotherapy

Contact Info

Product

Resources

About