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Xiao-Rong Yang
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P01 - Antibody Drug Conjugates, Novel Therapeutics and Cytotoxics (ID 227)
- Event: WCLC 2020
- Type: Posters
- Track: Antibody Drug Conjugates, Novel Therapeutics and Cytotoxics
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P01.16 - Tamoxifen Might Enhance the Effect of EGFR-TKIs on EGFR-Mutant NSCLC Cells (ID 1004)
00:00 - 00:00 | Author(s): Xiao-Rong Yang
- Abstract
Introduction
Postmenopausal females with epidermal growth factor receptor (EGFR) mutant non small cell lung cancer (NSCLC) have longer progression free survival than premenopausal females when they receive EGFR tyrosine kinase inhibitors (TKIs) treatment. The level of estrogen and estrogen receptors (ERs) in lung cancer tissue might affect the response of EGFR-TKIs. This experiment aims to study the expression of ERs in EGFR-mutant NSCLC cell lines and explore the method to improve the efficacy of EGFR-TKIs from the perspective of estrogen.
Methods
The level of ERs protein in the nucleus, cytoplasm and membrane of EGFR-mutant NSCLC cell lines was evaluated by western blot. The EGFR-mutant NSCLC cell lines were treated with anti-estrogen, EGFR-TKIs, or the combination; the effect of treatment on cells viability was determined by CCK8 arrays.
Results
Both ERα and ERβ expressed in multiple NSCLC cell lines. The ERα protein in MCF7 cell line was as much as the ERβ protein, but the ERα protein in EGFR-mutant NSCLC cell lines was much less than the ERβ protein. ERβ was detected in nucleus, cytoplasm and membrane of EGFR-mutant NSCLC cell lines. Compared with Tamoxifen or Erlotinib alone, the combination of the two drugs significantly inhibited the viability of PC9 cell line; compared with Tamoxifen or Osimertinib alone, the combination significantly inhibited the viability of H1975 cell line. But Fulvestrant showed little effect on the prohibition of both PC9 cell line and H1975 cell line.
Conclusion
Tamoxifen might improve the efficacy of EGFR-TKIs on EGFR-mutant NSCLC cell lines. Estrogen might interact with EGFR pathway through the ERβ in the cytoplasm and membrane to promote the proliferations of EGFR-mutant NSCLC cells. More information will be shown in the conference.
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P85 - Targeted Therapy - Clinically Focused - MET (ID 262)
- Event: WCLC 2020
- Type: Posters
- Track: Targeted Therapy - Clinically Focused
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P85.07 - Neutrophils Counts Deregulated by C-met TKIs and the Variation Predicts Treatment Response in NSCLC (ID 1089)
00:00 - 00:00 | Presenting Author(s): Xiao-Rong Yang
- Abstract
Introduction
C-met receptor tyrosine kinase (TKIs) which currently used in the clinic is an inhibitor of MET oncogene. Recently, researchs on mice have reported that c-met inhibitor impairs reactive neutrophil recruitment in tumor microenvironment. Mechanically, c-met signal aggravates T-cell infiltration in tumors by recruiting neutrophils. The change of circulating neutrophils can also been detected in peripheral blood on animal models which related to treatment response. However, this phenomenon and potential of predicting treatment response has not been proved in humans.
Methods
Patients had been enrolled who undertaken two off-label high selective c-met TKIs clinical trials until March, 2020. The clinical signature, treatment response, absolute neutrophil counts, absolute lymphocyte counts and neutrophil lymphocyte ratio (NLR) had been collected in baseline and one cycle treatment later.
Results
Conclusion
In total, 39 patients had been included and all of them were diagnosed as NSCLC in advanced stage. 11 of 29 evaluated as partial response according to RECIST 1.0, 18 stable disease and 10 progressive disease, respectively. The absolute neutrophil counts are downregulated after one cycle c-met TKIs treatment (p=0.006). NLR is also downregulated but not reach significance level (p=0.132). The absolute lymphocyte counts seem merely change (p=0.502). The variation of deregulated neutrophils is significant in responders (OR=0.45, [95% CI: 0.25, 0.79], p=0.006). However, neutrophils variation is not corelated with PFS by univariate cox analysis (HR=0.98, [95%CI: 0.78, 1.23], p=0.98)
C-met TKIs deregulated the absolute neutrophil counts and NLR in peripheral blood. The variation of deregulated neutrophils may predict treatment response but not PFS.
