Program Official
Principal Investigator
Bob S
Carter
Awardee Organization
Massachusetts General Hospital
United States
Fiscal Year
2022
Activity Code
U01
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date
NIH RePORTER
For more information, see NIH RePORTER Project 5U01CA230697-05
Liquid Biopsy for treatment stratification of IDH1.R132H and EGFRvIII mutant gliomas
Summary Extracellular vesicles (EVs) and cell free DNA have emerged as a promising surrogate for the tissue biopsy, potentially enabling non-invasive, real-time cancer monitoring. Most cancer cells release high levels of EVs and cell-free DNA into circulation that carry molecular constituents of the parent tumor. Gliomas are among the most lethal of cancers and despite improved survival associated with surgery, utilizing intraoperative MR imaging guidance, as well as the postoperative use of the alkylating agent temozolomide, in combination with conformal radiation therapy and the angiogenesis inhibitor bevacizumab, glial tumors remain uniquely morbid, costly, and incurable. Brain tumor biopsy, necessary for clinical information, is itself associated with substantial morbidity and mortality. Consequently, there is a crucial need for more effective ways to determine the mutational landscape of early-stage tumors, via minimally invasive platforms, allowing for effective follow-up and biomarker-based care. The main goal of this proposal is to optimize liquid biopsy assays for the IDH1.R132H and EGFRvIII mutations in partnership with industry. This alliance includes Exosome Diagnostics, an industry leader in EV-based cancer diagnostics, offering ready capacity to develop and manufacture in-vitro diagnostic assays, and the Department of Neurosurgery at Massachusetts General Hospital, a pioneer in developing liquid biopsy signatures for brain cancer. These teams bring in their multidisciplinary expertise, innovative technologies and complementary resources to carry out the proposed work.
Publications
- Batool SM, Yekula A, Khanna P, Hsia T, Gamblin AS, Ekanayake E, Escobedo AK, You DG, Castro CM, Im H, Kilic T, Garlin MA, Skog J, Dinulescu DM, Dudley J, Agrawal N, Cheng J, Abtin F, Aberle DR, Chia D, Elashoff D, Grognan T, Krysan K, Oh SS, Strom C, Tu M, Wei F, Xian RR, Skates SJ, Zhang DY, Trinh T, Watson M, Aft R, Rawal S, Agarwal A, Kesmodel SB, Yang C, Shen C, Hochberg FH, Wong DTW, Patel AA, Papadopoulos N, Bettegowda C, Cote RJ, Srivastava S, Lee H, Carter BS, Balaj L. The Liquid Biopsy Consortium: Challenges and opportunities for early cancer detection and monitoring. Cell reports. Medicine. 2023 Oct 17;4(10):101198. Epub 2023 Sep 15. PMID: 37716353
- Song J, Cho MH, Cho H, Song Y, Lee SW, Nam HC, Yoon TH, Shin JC, Hong JS, Kim Y, Ekanayake E, Jeon J, You DG, Im SG, Choi GS, Park JS, Carter BC, Balaj L, Seo AN, Miller MA, Park SY, Kang T, Castro CM, Lee H. Amplifying mutational profiling of extracellular vesicle mRNA with SCOPE. Nature biotechnology. 2024 Oct 7. Epub 2024 Oct 7. PMID: 39375445