Expression of the epidermal growth factor receptor family in prostate carcinoma before and during androgen-independence

Abstract

Novel palliative strategies for patients with androgen-independent prostate cancer (AIPC) include targeting the epidermal growth factor receptor (EGFR) family. The aim of the present study was to investigate intrapatient changes of EGFRs during the development of AIPC. In total, 106 symptomatic AIPC patients were identified in whom prostatic biopsies (adenocarcinoma) were available both before the start of androgen deprivation (PRTR biopsy) and after the development of AIPC (AIPC biopsy). All four known subgroups of the EGFR family were determined by immunohistochemistry (IHC): c-erbB-1 (EGFR), c-erbB-2 (HER2/neu), c-erbB-3 (HER3) and c-erbB-4 (HER4). Moderate to strong membrane-specific staining was recorded semiquantitatively (o10% vs X10% ¼ IHC stained tumour cells: 'negative' vs 'positive' staining). The medical records were reviewed for clinical variables. During the development of AIPC, intrapatient changes occurred in two opposite directions for each of the four EGFRs: negativity changed to positivity, and vice versa, statistically significant only for the increase of c-erbB-1 expression (P ¼ 0.001). The c-erbB-2 expression in the AIPC biopsy was associated with a significantly shorter survival from the time of the AIPC biopsy (P ¼ 0.029). Our results support ongoing therapeutic attempts of EGFR inhibition in subgroups of patients with prostate cancer. Further research is needed to understand the function of EGFRs in this malignancy.

Lentiviruses with trastuzumab bound to their envelopes can target and kill prostate cancer cells

“…Furthermore, in prostate cancer cell lines, we found that androgen-sensitive LNCaP cells and castration-resistant C4-2 cells also overexpressed this protein (Figure 3). Our findings are consistent with the majority of patient-related reports in literature, [5][6][7][8]10,11 as well as some in vitro and animal model studies. 13,48,49 Furthermore, it has been recently reported that in men with long-term follow-up after HER-2 targeting of prostate cancer K-x Zhang et al radical prostatectomy, HER-2 expression when combined with percentage DNA index can be used clinically for prediction of progression, metastasis and prostate cancerspecific death.…”

“…In prostate cancers, overexpression of HER-2 has been reported to be associated with progression to androgen independence, [5][6][7][8]10,11 although some contradictory results have also been reported. 39,40 To normalize variables such as fixation and staining procedures, which could account for the reported differences, we used a TMA approach where 105 unique prostate tissue cores from 35 patients were immunostained for HER-2 simultaneously.…”

“…[5][6][7][8][9][10][11] Overexpression of HER-2, which causes activation of the PI3k/AKT pathways and promotion of cell proliferation, has been proposed to be a survival factor for prostate cancer cells in the absence of androgens. 10,12 Moreover, this can lead to the activation of the androgen receptor and enhancement of binding of this nuclear receptor to the promoters of androgenregulated genes.…”

“…13 Overall, overexpression of HER-2 in prostate cancer samples has been associated with lower survival. 7 Although trastuzumab (Herceptin), a humanized monoclonal antibody, which neutralizes the HER-2 receptor, has been shown to be very effective in treating breast cancers, treatment of patients with prostate cancer showed poor efficacy. 14 Furthermore, systematic administration of trastuzumab, especially in combination with other chemotherapeutic drugs, caused serious side effects, such as cardiotoxicity.…”

Engineering and characterization of a bispecific HER2 × EGFR‐binding affibody molecule

“…The bs affibody molecule should also have the potential to target two tumourassociated target proteins on the same cell. For certain tumour types, variable expression levels, but rather frequent expression, of both HER2 and EGFR have been reported [14][15][16][17][18][19], and bs targeting could thus be a valuable strategy to increase the efficiency in cancer imaging or therapy.…”