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
5520 - Patient’s Usability Test results of a CINV Diary Application For Smartphones
Presenter: Paz Fernandez
Session: Poster Display session 3
Resources:
Abstract
2323 - Colorectal Telephone Assessment Pathway (CTAP) - A viable means of shortening time to a definitive diagnosis of Colorectal Cancer (CRC)
Presenter: Harriet Watson
Session: Poster Display session 3
Resources:
Abstract
6119 - Cancer Nursing and Social Media: Capturing the Zeitgeist
Presenter: Mark Foulkes
Session: Poster Display session 3
Resources:
Abstract
1776 - Examination of mobile applications on breast cancer
Presenter: AYDANUR AYDIN
Session: Poster Display session 3
Resources:
Abstract
4128 - E-health effectiveness to increase patient adherence for immunotherapy; a cost-benefit study.
Presenter: Maria José Dias
Session: Poster Display session 3
Resources:
Abstract
3219 - Experiences of internet-based stepped care among individuals with recently diagnosed cancer and symptoms of anxiety and/or depression
Presenter: Anna Hauffman
Session: Poster Display session 3
Resources:
Abstract
5010 - What do cancer patients know about their immunotherapy treatment?
Presenter: Mónica Arellano
Session: Poster Display session 3
Resources:
Abstract
4503 - Prospective Comparison of Travel Burden, Cost and Time to Obtain Tumor Board Treatment Plan Through In-Person Visits vs. an AI Enabled Health Technology (N=1803)
Presenter: Rajendra Badwe
Session: Poster Display session 3
Resources:
Abstract
4123 - Cancer care through the fire and flames: 3-year experience in the utilisation of electronic consultation and referral system at the Red Zone in Southern Thailand
Presenter: Nanthiya Rattanakhot
Session: Poster Display session 3
Resources:
Abstract
2087 - The effect of e-mobile education on the quality of life in women with breast cancer
Presenter: Derya ÇInar
Session: Poster Display session 3
Resources:
Abstract