Abstract 1462
Background
Esophageal squamous cell carcinoma (ESCC) with high mortality is particularly prevalent in China and the prognosis is poor. Although genetic amplification and overexpression of the fibroblast growth factor 19 (FGF19) gene are found in ESCC, mechanisms that contribute to such functional alterations remain elusive.
Methods
Gene-Panel Sequencing was used to detect genetic variants that may be associated with a risk of ESCC. The effect of proliferation inhibition of LY2874455, which is inhibitor of fibroblast growth factor receptors (FGFR), was assessed in ESCC patient-derived cell (PDC) and xenograft (PDX) models. Autophagic activity was evaluated by immunoblotting for microtubule-associated protein 1 light chain 3 (LC3) and p62.
Results
Using Gene-Panel Sequencing of 161 FFPE tissues, we found that FGF19 copy number amplified in almost 30% ESCC. Pharmacological of FGF19/FGFR by LY2874455 significantly induces repression of FGF19 amplificated ESCC progression in either PDC or PDX models. Mechanistic study revealed that treatment with LY2874455 induced activity of autophagy by inhibiting the ERK/MAPK pathway not by AKT pathway.
Conclusions
Our findings reveal that FGF19 amplification inhibits autophagic activity by increasing the phosphorylation level of ERK, which may play an essential role in the pathogenesis of ESCC. Using FGFR inhibitor may represent an effective strategy to suppress FGF19 amplificated ESCC development and progression.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
The Major Project of Health Commission of Zhejiang Province of China (No. WKJ-ZJ-1902), the Public Welfare Technology Foundation of Zhejiang Province of China (No. 2017C34001), Zhejiang high-level innovative talent program, and the 1022 program of Zhejiang Cancer Hospital.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
4600 - Patterns and outcomes related to rapid progressive disease in a cohort of advanced solid tumors treated with immune checkpoint inhibitors (ICIs).
Presenter: Lucio Ghiglione
Session: Poster Display session 3
Resources:
Abstract
3547 - Real World Outcomes of Immune-Related Adverse Events (irAEs) among Patients Receiving Immune Checkpoint Inhibitors (ICIs) in Hospital Settings
Presenter: Saby George
Session: Poster Display session 3
Resources:
Abstract
1124 - Sex-based heterogeneity of efficacy of anticancer immunotherapy
Presenter: Fabio Conforti
Session: Poster Display session 3
Resources:
Abstract
4133 - Comparative efficacy and safety of PD-1/PD-L1 inhibitors for patients with solid tumors: a systematic review and Bayesian network meta-analysis
Presenter: Qingyuan Huang
Session: Poster Display session 3
Resources:
Abstract
2548 - Excess weight and efficacy of anti-PD-1 antibodies in advanced cancer patients
Presenter: Jacobo Rogado
Session: Poster Display session 3
Resources:
Abstract
2228 - Safety and efficacy of anti-PD-1 inhibitor ABBV-181 in lung and head and neck carcinoma
Presenter: Antoine Italiano
Session: Poster Display session 3
Resources:
Abstract
2333 - Efficacy and safety of immune checkpoint inhibitors (ICIs) for treatment of advanced solid tumours in octogenarian patients
Presenter: Soraya Mebarki
Session: Poster Display session 3
Resources:
Abstract
4847 - Association of programmed cell death 1 (PD-1) inhibitor therapy with overall survival (OS) in stage IV melanoma treated with targeted therapies
Presenter: Aracelis Torres
Session: Poster Display session 3
Resources:
Abstract
2215 - Clinical outcomes of immune checkpoint inhibitors in older and younger patients with advanced solid tumours in a real-life setting
Presenter: Pauline Corbaux
Session: Poster Display session 3
Resources:
Abstract
2881 - Impact of corticosteroids and antibiotics on efficacy of immune-checkpoint inhibitors in advanced non-small cell lung cancer
Presenter: Joaquin Mosquera Martinez
Session: Poster Display session 3
Resources:
Abstract