title: Imaging of HER2 may improve the outcome of external irradiation therapy for prostate cancer patients.
abstract: Prostate cancer (PCa) is the most common type of cancer among males. Human epidermal growth factor receptor type 2 (HER2) expression in PCa has been reported by several studies and its involvement in the progression towards androgen-independent PCa has been discussed. External irradiation is one of the existing therapies, which has been demonstrated to be efficient in combination with androgen deprivation therapy for the treatment of advanced PCa. However, 20-40% of patients develop recurrent and more aggressive PCa within 10 years. The current study investigates the involvement of HER2 in survival and radioresistance in PCa cells and we hypothesized that, by monitoring HER2 expression, treatment may be personalized. The PCa cell lines, LNCap, PC3 and DU-145, received a 6 Gy single dose of external irradiation. The number of PC3 cells was not affected by a single dose of radiation, whereas a 5-fold decrease in cell number was detected in LNCap (P<0.00001) and DU-145 (P<0.0001) cells. The HER2 expression in PC3 exhibited a significant increase post irradiation, however, the expression was stable in the remaining cell lines. The administration of trastuzumab post-irradiation resulted in a 2-fold decrease in the PC3 cell number, while the drug did not demonstrate additional effects in LNCap and DU-145 cells, when compared with that of irradiation treatment alone. The results of the present study demonstrated that an increase in membranous HER2 expression in response to external irradiation may indicate cell radioresistance. Furthermore, imaging of HER2 expression prior to and following external irradiation may present a step towards personalized therapy in PCa.
authors.affiliation: Department of Medicinal Chemistry, Preclinical PET Platform, Uppsala University, Uppsala 751 83, Sweden.
authors.forename: Jennie
authors.initials: J
authors.lastname: Andersson
authors.affiliation: Department of Medicinal Chemistry, Preclinical PET Platform, Uppsala University, Uppsala 751 83, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Rosestedt
authors.affiliation: Department of Medicinal Chemistry, Preclinical PET Platform, Uppsala University, Uppsala 751 83, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Orlova
keywords: external irradiation; human epidermal growth factor receptor type 2; molecular imaging; prostate cancer