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.

Trastuzumab cotreatment improves survival of mice with PC‐3 prostate cancer xenografts treated with the GRPR antagonist 177Lu‐DOTAGA‐PEG2‐RM26

“…In a recent in vitro study, Andersson et al . showed that HER2 expression in PC‐3 cells increased significantly after external irradiation leading to resistance to therapy …”

“…In agreement with clinical data, antiHER2 treatment did not induce any measurable therapeutic effect, however, IHC HER2 staining demonstrated that even short treatment with trastuzumab eliminated HER2 expression. Interestingly, in agreement with our in vitro data, HER2 expression increased shortly after radiotherapy in the group treated with the radiopeptide but was not detected in the group treated with the combination of radiopeptide and trastuzumab. The absence of HER2 expression shortly after therapy could be attributed to continued saturation of HER2 with trastuzumab.…”

Combinatorial Microenvironments Impose a Continuum of Cellular Responses to a Single Pathway-Targeted Anti-cancer Compound

“…A549 non-small cell lung cancer (NSCLC) cell line, which has genomic amplification of EGFR and HER2 and was used to show that NSCLC could benefit from lapatinib treatment (Diaz et al, 2010). PC3 prostate cancer cell line that was used to show that radiation resistant prostate cancers express HER2, and may benefit from HER2 targeted therapy (Andersson et al, 2015). 60 replicate spots were printed for each microenvironment composed of pairwise combinations of four ECM and seven ligands on either 2500 Pa or 40 kPa elastic modulus substrata.…”

Molecularly targeted radiosensitization chances towards gene aberration-due organ confined/regionally advanced prostate cancer radioresistance

“…Among further developments of customized radiosensitizers, just those molecularly targeting the identified PCa cell radioresistance-linked individual gene aberrations will enhance the PCa radiation therapy lasting effectiveness (1)(2)(3)(4)(5)(6)(7)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19).…”

“…Despite external beam radiation therapy (EBRT) delivery technological advances -from intensity modulated therapy to tomotherapy and image-guided robot 6D radiotherapy, allowing high energy radiation delivery meanwhile minimising side-effects -the prostate cancer (PCa) biochemical/clinical relapse percentage remains nowadays high (post-EBRT PCa recurrence at 20-40 %) (1)(2)(3).…”