Abstract 2426
Background
Suppression of cancer metastasis is an urgent therapeutic need because metastasis is a major cause of high mortality in different types of cancers including lung cancer. Overexpression of a disintegrin and metalloprotease 9 (ADAM9), a member of the ADAM family of type I transmembrane proteins, is observed in many cancers and correlates with lung cancer brain metastasis. Since it contributes to tumorigenesis due to its ability in cleaving and releasing a number of molecules that involves cancer progression, it would be a potential target for lung cancer treatment.
Methods
We have performed the genome-wide approach to explore ADAM9-regulated genes. Moreover, we have developed small compounds as ADAM9 inhibitors to target ADAM9’s catalytic domain using virtual screening and evaluated them by inhibiting ADAM9-mediated downstream pathways.
Results
Overexpression of ADAM9 in lung cancer cells promotes tumor metastasis. Several ADAM9-mediated pathways are investigated from RNA-seq analysis. In the other hand, we have validated the potency of developed small compounds in reducing ADAM9 protease activity, cancer cell growth, and cell migration. In tumor animal models, ADAM9 inhibitors exhibited high efficacy to reduce cancer progression in animals bearing lung tumors. Notably, no liver and kidney toxicity were detected, suggesting no severe toxicity after drug treatment.
Conclusions
We demonstrate inhibition of ADAM9 activity by potential ADAM9 inhibitor provide anti-lung tumor benefits in vitro and in vivo. Notably, ADAM9 inhibitor treatment has no systemically acute toxicity in mice. Thus, targeting ADAM9 provides a potential strategy for lung cancer treatment.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
The National Health Research Institutes, Taiwan.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
1122 - Platelets from metastatic cancer patients have increased aggregation and activation
Presenter: Meera Chauhan
Session: Poster Display session 3
Resources:
Abstract
2671 - Luminal B breast cancer prognosis prediction by comprehensive analysis of Homeobox genes
Presenter: Ayako Nakashoji
Session: Poster Display session 3
Resources:
Abstract
2650 - Long non-coding RNA E2F4as promotes tumor progression and predicts patient prognosis in human ovarian cancer
Presenter: Sun-Ae Park
Session: Poster Display session 3
Resources:
Abstract
1462 - FGF19 promotes esophageal squamous cell carcinoma progression by inhibiting autophagy
Presenter: Lisha Ying
Session: Poster Display session 3
Resources:
Abstract
5787 - Proof of concept on the role of ex vivo lung cancer spheroids, cytokines expression and PBMCs profiling in monitoring disease history and response to treatments.
Presenter: Raimondo Di Liello
Session: Poster Display session 3
Resources:
Abstract
5253 - Circulating microRNAs related to DNA damage response as predictors of survival in metastatic non- small cell lung cancer patients treated with platinum-based chemotherapy
Presenter: Dimitris Mavroudis
Session: Poster Display session 3
Resources:
Abstract
5286 - Prognostic value of CTCs in advanced NSCLC patients treated with platinum-based chemotherapy
Presenter: Silvia Calabuig-Fariñas
Session: Poster Display session 3
Resources:
Abstract
5781 - Exosomes in NSCLC as a source of biomarkers
Presenter: Elena Duréndez
Session: Poster Display session 3
Resources:
Abstract
1447 - The role of Pim-1 in the development and progression of papillary thyroid carcinoma
Presenter: Xin Zhu
Session: Poster Display session 3
Resources:
Abstract
1323 - Development and Validation of a RNA-Seq Based Prognostic Signature in Neuroblastoma
Presenter: Jian-Guo Zhou
Session: Poster Display session 3
Resources:
Abstract