PRaG 3.0 therapy for human epidermal growth factor receptor 2-positive metastatic pancreatic ductal adenocarcinoma:A case report

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.

SPAG9 promotes prostate cancer growth and metastasis

Sperm-associated antigen 9(SPAG9)expression is increased in prostate tissues of prostate cancer patients.This experimental study aimed to investigate the role of SPAG9 in bone metastasis of prostate cancer.Immunohistochemical analysis showed that SPAG9 staining was positive in 81.67%of 240 cases of prostatic carcinoma but only in 6.67%of 120 cases of benign prostate hyperplasia.Strong PAG9 staining was positively correlated with Gleason score and bone metastasis in 240 prostate cancer patients(p<0.05),but not with the age or serum prostate-specific antigen level(p>0.05).PC-3 cells were transfected with shRNA against SPAG9,and CCK-8 assay in triplicate showed that PC-3 cell viability was inhibited by SPAG9 knockdown.In addition,transwell assay in triplicate showed that PC-3 cell invasion was inhibited by SPAG9 knockdown.Furthermore,total 2×106 PC-3 cells were injected subcutaneously into the right flank of nude mice which were randomly divided into three groups(N=8)and treated by intratumoral injection of SPAG9 shRNA,control shRNA or PBS,respectively.SPAG9 shRNA inhibited the growth,invasion and angiogenesis while promoted apoptosis of xenografted PC-3 cells.SPAG9 knockdown led to the upregulation of E-cadherin and the downregulation of MMP2 and vimentin in xenografted tumors.In conclusion,this is the first study to provide evidence that SPAG9 promotes bone metastasis of prostate cancer,and SPAG9 is a promising target to prevent or treat bone metastasis of prostate cancer.