Page 9 - I. Chemical biology and drug discovery

Elucidation of resistance and its mechanism of
RTKi by identifying new target protein
Tae Young Kim 1 , Eunsun Ji 2 , Jinyoung Kim 2 , Jongshin Yoo 2 , Marcell Szasz 3 , György Marko-Varga 4 , and Ho Jeong Kwon 1,*
1 Chemical Genomics Global Research Laboratory, Department of Biotechnology, College of Life Science & Biotechnology, Yonsei University, Seoul 120-749, Korea,
2 Korea Basic Science Institute, Cheongwon-Gun, Chungbuk 28119, Korea,
3 MTA-TTK Lendület Cancer Biomarker Research Group, Hungarian Academy of Sciences, 1117 Budapest, Hungary,
4 Clinical Protein Science & Imaging, Biomedical Center, Department of Measurement Technology and Industrial Electrical Engineering, Lund University, BMC C13, SE-221 84 Lund, Sweden,
BACKGROUND AIM
▶ RTKi resistance acquires 8 ~14 months after the - To reveal the resistance for receptor tyrosine kinase inhibitor
primary treatment (RTKi), treating in NSCLC (Non small cell lung cancer) patients
▶ Patients rapidly develop drug resistance - To elucidate its mechanism by identifying a new target protein
▶ Needs for a new drug resistant machanism with label- free DARTS LC-MS/MS SWATH analysis.
with another target proteins besides EGFR
METHODS

RESULTS

REFERENCES
Graham McMahon., et al, NEJM (2011)
Brett Lomenick., et al, PNAS (2009)
ACKNOWLEDGEMENTS
Supported by NRF (MSIP;2015K1A1A2028365,
2016K2A9A1A03904900) and BK21 PLUS.
Contact information
*Presenter: kty1273@yonsei.ac.kr
*Correspondence: kwonhj@yonsei.ac.kr
CONCLUSION

▶ We performed DARTS LC-MS/MS with SWATH of data independant analysis (DIA) ▶ Both methods (DARTS and CETSA) also revealed erlotinib has the same
and identified a novel binding protein of erlotinib that may underlie NSCLC resistance binding affinity for Protein P and EGFR (0.1 μM).
▶ This method takes advantage of an un-modified compound to rapidly sort out ▶ Knock-down Protein P suppressed proliferation in H1299 (High exp).
target candidates with the auto-quantify program of SWATH analysis Over-expression of Protein P in HCC827 cells (Low exp) ameliorated
the anti-proliferative effect of erlotinib and led to drug resistance.
In conclusion, this study demonstrates that Protein P could be a potential biomarker
of RTKi resistance to promote proliferative effect of RTKi’s resistant cancer cells.