Principal Investigator

David T
Wong
Awardee Organization

University Of California Los Angeles
United States

Fiscal Year
2021
Activity Code
UH3
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date

Advancing EFIRM-Liquid Biopsy (eLB) to a CLIA-Certified Laboratory Developed Test (eLB-LDT) for Detection of Actionable EGFR Mutations in NSCLC Patients

Malignant transformation of normal cells are driven by oncogenic mutations of key cellular genes where therapeutics are actively being developed to target these mutations for interventions that will improve morbidity and/or mortality. The current clinical practice to interrogate these “actionable mutations” is by tumor biopsy followed by genotyping which is invasive and at times access restrictive, challenging, subject to sampling errors and may simply not possible. Liquid biopsy is a rapidly emerging field to access actionable mutations in tumors minimal/non-invasively in bodily fluids based on circulating tumor DNA (ctDNA). This UH2/UH3 application is responsive to the PAR-15-095 to advance the translational and clinical development of a matured academic laboratory assay, the EFIRM-Liquid Biopsy (eLB) to a “Clinical Laboratory Improvement Amendment” (CLIA)-certified laboratory developed test (eLB-LDT), in the UCLA Molecular Diagnostic Laboratories (MDL), a CLIA-certified/ College of American Pathologists (CAP)-accredited Laboratory. The eLBLDT will be evaluated in a clinical context of use to interrogate actionable mutations in the EGFR gene of NSCLC patients at the VA Greater Los Angeles Healthcare System (VA GLA). It is important to advance academic assays for cancer detection, diagnosis and treatment to regulated clinical assays that will provide novel capabilities to physicians to impact health of their patients. Our proposal is to advance a matured academic assay, EFIRM-Liquid Biopsy (eLB) that delivers the best performance technology to detect oncogenic mutations, to become a CLIA-certified laboratory developed test (LDT), the EFIRM-Liquid Biopsy laboratory developed test (eLB-LDT). eLB detects actionable EGFR mutations in NSCLC patients with 100% concordance with biopsy-based genotyping, outperforms current technologies for liquid biopsy. The clinical validation study will be conducted at the UCLA Medical Center and VA Greater Los Angeles Healthcare System (VA GLA) where 20% of patients with adenocarcinoma subtype of non-small cell lung carcinoma (NSCLC) harbor TKI-responsive mutations in the EGFR gene. The eLB-LDT technology if validated, may replace current practice of liquid biopsy for EGFR genotyping as it has the best performance, minimal or non-invasive, rapid, inexpensive and self-contained permitting the detection of the most common EGFR gene mutations that are treatable with TKI such as Gefitinib or Erlotinib to effectively extend the progression free survival of lung cancer patients. Two Specific Aims are in place to achieve these goals. Aim 1/UH2 is to adapt the academic EFIRM-Liquid Biopsy (eLB) technology to become a CLIA-certified assay in the UCLA Diagnostics Molecular Pathology Laboratory and to determine analytical and clinical performance. Aim 2/UH3 is to analytically and clinically validate eLB-LDT at the clinical sites (UCLA and VA GLA).

Publications

  • Wei F, Strom CM, Cheng J, Lin CC, Hsu CY, Soo Hoo GW, Chia D, Kim Y, Li F, Elashoff D, Grognan T, Tu M, Liao W, Xian R, Grody WW, Su WC, Wong DTW. Electric Field-Induced Release and Measurement Liquid Biopsy for Noninvasive Early Lung Cancer Assessment. The Journal of molecular diagnostics : JMD. 2018 Nov;20(6):738-742. Epub 2018 Oct 8. PMID: 30309763
  • Salfer B, Li F, Wong DTW, Zhang L. Urinary Cell-Free DNA in Liquid Biopsy and Cancer Management. Clinical chemistry. 2022 Dec 6;68(12):1493-1501. PMID: 36213956
  • Nonaka T, Wong DTW. Saliva diagnostics: Salivaomics, saliva exosomics, and saliva liquid biopsy. Journal of the American Dental Association (1939). 2023 Aug;154(8):696-704. PMID: 37500232
  • Nonaka T, Wong DTW. Saliva Diagnostics. Annual review of analytical chemistry (Palo Alto, Calif.). 2022 Jun 13;15(1):107-121. PMID: 35696523
  • Dawes C, Wong DTW. Role of Saliva and Salivary Diagnostics in the Advancement of Oral Health. Journal of dental research. 2019 Feb;98(2):133-141. PMID: 30782091
  • Wang Z, Li F, Rufo J, Chen C, Yang S, Li L, Zhang J, Cheng J, Kim Y, Wu M, Abemayor E, Tu M, Chia D, Spruce R, Batis N, Mehanna H, Wong DTW, Huang TJ. Acoustofluidic Salivary Exosome Isolation: A Liquid Biopsy Compatible Approach for Human Papillomavirus-Associated Oropharyngeal Cancer Detection. The Journal of molecular diagnostics : JMD. 2020 Jan;22(1):50-59. PMID: 31843276
  • Nonaka T, Wong DTW. Liquid Biopsy in Head and Neck Cancer: Promises and Challenges. Journal of dental research. 2018 Jun;97(6):701-708. Epub 2018 Mar 7. PMID: 29513618
  • Li N, Guha U, Kim C, Ye L, Cheng J, Li F, Chia D, Wei F, Wong DTW. Longitudinal Monitoring of EGFR and PIK3CA Mutations by Saliva-Based EFIRM in Advanced NSCLC Patients With Local Ablative Therapy and Osimertinib Treatment: Two Case Reports. Frontiers in oncology. 2020 Jul 24;10:1240. doi: 10.3389/fonc.2020.01240. eCollection 2020. PMID: 32793495
  • Li F, Yoshizawa JM, Kim KM, Kanjanapangka J, Grogan TR, Wang X, Elashoff DE, Ishikawa S, Chia D, Liao W, Akin D, Yan X, Lee MS, Choi R, Kim SM, Kang SY, Bae JM, Sohn TS, Lee JH, Choi MG, Min BH, Lee JH, Kim JJ, Kim Y, Kim S, Wong DTW. Discovery and Validation of Salivary Extracellular RNA Biomarkers for Noninvasive Detection of Gastric Cancer. Clinical chemistry. 2018 Oct;64(10):1513-1521. Epub 2018 Aug 10. PMID: 30097497
  • Li F, Wei F, Huang WL, Lin CC, Li L, Shen MM, Yan Q, Liao W, Chia D, Tu M, Tang JH, Feng Z, Kim Y, Su WC, Wong DTW. Ultra-Short Circulating Tumor DNA (usctDNA) in Plasma and Saliva of Non-Small Cell Lung Cancer (NSCLC) Patients. Cancers. 2020 Jul 24;12. (8). PMID: 32722209
  • Li F, Wei F, Grogan TR, Elashoff DE, Vu D, Vigerust DJ, Gupta R, Wong DTW. Proficiency Testing of Epidermal Growth Factor Receptor Mutations Detection in Saliva Using Spectrum Saliva Collector (SDNA-1000) and Preservative Solution Detected by Electric Field-Induced Release and Measurement. Biopreservation and biobanking. 2022 Oct;20(5):461-464. Epub 2022 Jul 26. PMID: 35878053
  • Cheng J, Swarup N, Li F, Kordi M, Lin CC, Yang SC, Huang WL, Aziz M, Kim Y, Chia D, Yeh YM, Wei F, Zheng D, Zhang L, Pellegrini M, Su WC, Wong DTW. Distinct Features of Plasma Ultrashort Single-Stranded Cell-Free DNA as Biomarkers for Lung Cancer Detection. Clinical chemistry. 2023 Nov 2;69(11):1270-1282. PMID: 37725931
  • Tu M, Cheng J, Chen YL, Jea WC, Chen WL, Chen CJ, Ho CL, Huang WL, Lin CC, Su WC, Ye Q, Deignan J, Grody W, Li F, Chia D, Wei F, Liao W, Wong DTW, Strom CM. Electric Field-Induced Release and Measurement (EFIRM): Characterization and Technical Validation of a Novel Liquid Biopsy Platform in Plasma and Saliva. The Journal of molecular diagnostics : JMD. 2020 Aug;22(8):1050-1062. Epub 2020 Jun 1. PMID: 32497715
  • Kaczor-Urbanowicz KE, Wei F, Rao SL, Kim J, Shin H, Cheng J, Tu M, Wong DTW, Kim Y. Clinical validity of saliva and novel technology for cancer detection. Biochimica et biophysica acta. Reviews on cancer. 2019 Aug;1872(1):49-59. Epub 2019 May 30. PMID: 31152821
  • Kim C, Xi L, Cultraro CM, Wei F, Jones G, Cheng J, Shafiei A, Pham TH, Roper N, Akoth E, Ghafoor A, Misra V, Monkash N, Strom C, Tu M, Liao W, Chia D, Morris C, Steinberg SM, Bagheri H, Wong DTW, Raffeld M, Guha U. Longitudinal Circulating Tumor DNA Analysis in Blood and Saliva for Prediction of Response to Osimertinib and Disease Progression in EGFR-Mutant Lung Adenocarcinoma. Cancers. 2021 Jul 3;13. (13). PMID: 34283064
  • Swarup N, Cheng J, Choi I, Heo YJ, Kordi M, Li F, Aziz M, Chia D, Wei F, Elashoff D, Zhang L, Kim S, Kim Y, Wong DTW. Multi-Faceted Attributes of Salivary Cell-free DNA as Liquid Biopsy Biomarkers for Gastric Cancer Detection. Research square. 2023 Jul 14. PMID: 37503289
  • Nonaka T, Wong DTW. Saliva-Exosomics in Cancer: Molecular Characterization of Cancer-Derived Exosomes in Saliva. The Enzymes. 2017;42:125-151. Epub 2017 Oct 9. PMID: 29054268