Abstract 3062
Background
Anthracycline/taxane-based chemotherapy is frequently used to treat breast cancer. However, not all patients respond to chemotherapy due to naturalor acquired chemo-resistance. Glutathione S-transferase P1(GSTP1), which belongs to the family of phase II metabolic enzymes, has been reported to function in detoxifying several anti-cancer drugs by conjugating them with glutathione.
Methods
We identified GSTP1 as a drug-resistance-related factor by microarray. Then, we used cell apoptosis and immunofluorescence staining to confirm the ability of GSTP1-containing exosomes in conferring drug resistance. And the knockdown of GSTP1 gene was performed to found the influence of drug-resistance. Furthermore, the role of GSTP1 and its relationship with exosomes was proved by analysed 40 pairs of breast cancer tissues by IHC. Then, the levels of GSTP1 in serum exosomes were detected in 28 patients treated with neoadjuvant chemotherapy(NAC).
Results
By microarray data, we found that GSTP1, which located in extracellular exosome, is higher in Adriamycin(ADR)-resistant cell line compared with its parental cell line. Then, we also confirmed a higher expression of GSTP1 protein in ADR-resistant cells by immunofluorescence staining and western blot. Moreover, the addition of GSTP1-containing exosomes can increase the resistance to ADR in sensitive cells. Also, we found that a higher expression GSTP1 in the PD/SD group than in the PR/CR group in 40 paired samples collected before and after chemotherapy. Similar results were obtained for the exosomal marker tumor susceptibility gene 101 protein (TSG101), which also increased in the cytoplasm after chemotherapy. We further explored the levels of GSTP1 in serum exosomes of 28 patients treated with anthracycline/taxane-based NAC, and discovered that the levels of GSTP1 in exosomes from patients in the PD/SD group were higher than those in the PR/CR group.
Conclusions
GSTP1-containing exosomes appeared to be essential in conferring resistance to anti-cancer drugs. We explored the predictive role of GSTP1 in circulating exosomes as a biomarker for chemo-sensitivity in patients treated with anthracycline/taxane-based chemotherapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Jinhai Tang.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
5063 - Does Nutritional Status Affect Treatment Tolarability, Response and Survival in Metastatic Gastric Cancer Patients? Results of Prospective Multicenter Study
Presenter: Senem Karabulut
Session: Poster Display session 2
Resources:
Abstract
2717 - Ramucirumab use in patients with Advanced Gastric Cancer (AGC) or gastro-oesophageal junction (GEJ) adenocarcinoma in Spain: RAMIS observational study
Presenter: Federico Longo Munoz
Session: Poster Display session 2
Resources:
Abstract
3187 - Gastrectomy plus chemotherapy versus chemotherapy alone for advanced gastric cancer with a single non-curable factor: Exploratory analysis in the patients who were enrolled in JCOG0705/KGCA01 phase III trial (REGATTA) and could continue chemotherapy
Presenter: Takaki Yoshikawa
Session: Poster Display session 2
Resources:
Abstract
4765 - A prospective observational study on the optimal maintenance strategy in HER2-positive advanced gastric cancer treated with trastuzumab based therapy
Presenter: Qian Li
Session: Poster Display session 2
Resources:
Abstract
3500 - Randomised phase 2 trial of first-line docetaxel, carboplatin, capecitabine (CTX) and epirubicin, oxaliplatin, capecitabine (EOX) in advanced esophagogastric adenocarcinoma (SEED)
Presenter: Peter Petersen
Session: Poster Display session 2
Resources:
Abstract
5197 - Ramucirumab in the treatment of refractory metastatic gastric cancer: results from the RamSelGa trial.
Presenter: Alexey Tryakin
Session: Poster Display session 2
Resources:
Abstract
2011 - Regorafenib in combination with Paclitaxel for beyond first-line treatment of advanced esophagogastric cancer (REPEAT): a phase Ib trial with expansion cohort
Presenter: Mohammed Khurshed
Session: Poster Display session 2
Resources:
Abstract
2117 - The relationship between the survival and fixed dosing of S-1 in advanced gastric cancer patients by pooled analysis using individual data from four Japanese randomized phase III trials
Presenter: Wataru Ichikawa
Session: Poster Display session 2
Resources:
Abstract
2669 - A Phase 1b Study of Oraxol in Combination with Ramucirumab in Patients with Gastric or Esophageal Cancers who failed previous chemotherapy
Presenter: Ming Huang Chen
Session: Poster Display session 2
Resources:
Abstract
3240 - Efficacy and safety of trifluridine/tipiracil (FTD/TPI) in European patients with heavily pretreated metastatic gastric cancer (mGC): an analysis of the TAGS study
Presenter: Maria Alsina
Session: Poster Display session 2
Resources:
Abstract