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Felix Lasitschka
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EP1.03 - Biology (ID 193)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Biology
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.03-30 - FAM83A and FAM83B as Prognostic Biomarkers and Potential New Therapeutic Targets in NSCLC (Now Available) (ID 587)
08:00 - 18:00 | Author(s): Felix Lasitschka
- Abstract
Background
Although targeted therapy improved survival rates in the last decade, non-small cell lung cancer (NSCLC) is still the most common cause of cancer related death. As most precision medicines lead to resistance, the challenge of identifying new targets for further effective therapies still remains. The FAMily with sequence similarity 83 (FAM83) members have recently been described as novel oncogenes in numerous human cancer specimens and shown to be involved in EGFR signaling. However, their function in cancer cells is largely unknown and especially their role in lung cancer remains unclear.
Method
Here, we investigated the expression and function of FAM83A and B in NSCLC. First, gene expression of the two FAM83 members was analyzed in a set of 362 NSCLC patients using qPCR. We further investigated relations in expression and their prognostic value using correlation and multivariate COX regression analyses. Functional assays in NSCLC cell lines were performed to analyze their involvement in proliferation, anchorage-independent growth, migration and the epidermal growth factor receptor (EGFR) pathway.
Result
We observed a highly increased gene expression level of FAM83A (ø = 68-fold) and FAM83B (ø = 20-fold) which resulted in poor survival prognosis (p < 0.0001 and p = 0.002). Correlation analysis showed poor relation between FAM83A and B in the two sub-histologies adenocarcinoma (ADC) and squamous cell carcinoma (SQCC) but confirmed correlation between FAM83A and B and EGFR expression levels in patients and cell lines. Their expression was further influenced by EGFR pathway signaling and mutation status. Both genes affected cell proliferation and FAM83A depletion resulted in reduced migration and AIG.
Conclusion
The results support the hypothesis that FAM83A and B have different specific functions in the histological subtypes of NSCLC and might be new therapeutic targets.
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P1.01 - Advanced NSCLC (ID 158)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.01-34 - Early Assessment of Therapy Response in Non-Small Cell Lung Cancer (NSCLC) via Longitudinal ctDNA Analysis (ID 2795)
09:45 - 18:00 | Author(s): Felix Lasitschka
- Abstract
Background
Quantifying circulating tumor DNA (ctDNA) is an emerging method to non-invasively assess treatment effect for solid tumors. Despite disease heterogeneity in NSCLC, we set out to identify a broadly applicable ctDNA-based method for disease monitoring. By employing plasma taken during early treatment cycles, we tested whether early response assessed by ctDNA level could predict treatment effect.
Method
Using a 197-gene NGS assay, the AVENIO ctDNA Surveillance Kit (For Research Use Only, not for use in diagnostic procedures), we measured ctDNA levels in post-treatment plasma samples based on variants identified at baseline.
We used samples from an observational German Lung Cancer Multi-Marker Study. In a cohort of 83 stage IV lung adenocarcinoma treated with first-line chemo or chemoradiation therapies, we evaluated the association between survival and ctDNA levels in the first available post-treatment plasma sample (median number of days after start of treatment = 23). We used a ctDNA-based monitoring algorithm, and applied it to an independent set of 22 late stage lung squamous cell carcinoma that also underwent chemo or chemoradiation therapies to further evaluate the algorithm in different histology subtypes.
Result
We divided the 83 adenocarcinoma cohort into training (n=53) and test (n=30) sets. We found that subjects with longer progression free survival (PFS) had mean allele fraction (AF) < 1% in the training set. We applied the classifier to our adenocarcinoma test set and found that subjects with mean AF < 1% had longer PFS (HR 0.35; 95% CI 0.12 - 0.93; log-rank P = 0.028) and overall survival (OS) (HR 0.29; 95% CI 0.09 - 0.89; log-rank P= 0.021).
Using cutoffs identified in adenocarcinoma, we applied the same algorithms to the squamous cell carcinoma cohort. Subjects with mean AF < 1% had longer PFS (HR 0.26; 95% CI 0.10 - 0.71; log-rank P = 0.005) and OS (HR 0.12; 95% CI 0.05 - 0.51; log-rank P= 0.001).
Conclusion
Even in heterogeneous diseases such as NSCLC, changes in ctDNA levels in response to treatment may prove to be a valuable way of identifying subjects who may not benefit, before current standard of care methods like computed tomography (CT) scan. Future prospective studies to confirm these results are warranted.
