fairfolio
Saved Projects

Novel Strategies for the Reversal of Cancer Cell Immortality

CSEF · 2023 Biochemistry/ Molecular Biology Honorable_mention Award

Wu Samuel · 12

Overview

Glioblastoma (GBM) is the most common malignant adult brain tumor. With minimal clinical innovation, the prognosis for GBM patients remains grim. However, there is a commonality between 83% of GBMs: Telomerase Reverse Transcriptase promoter (TERTp) mutations. TERT, the catalytic component of telomerase, is responsible for telomere elongation and maintenance. The TERTp mutation creates a de novo ETS motif, allowing the GA-binding protein (GABP) transcription factor complex to specifically bind and reactivate the mutant allele. While direct targeting of telomerase has proven broadly toxic, targeting GABP to silence mutant TERTp overexpression is a potential alternative. However, direct small-molecule inhibition of transcription factors like GABP is challenging. To overcome this therapeutic barrier, I designed, engineered, and evaluated a GABPB1L transactivation-domain-null dominant-negative (B1-DN) transgene. I hypothesize that the B1-DN will sterically displace wildtype GABPB1L from the mutant TERTp, resulting in loss of TERT expression. Indeed, the B1-DN reduced TERT expression by up to 75% in TERTp mutant GBM, melanoma, and bladder cancer cell lines, but not in TERTp wildtype cells. This inhibitory effect was sustained throughout a 60-day time course, shortening telomeres throughout. Furthermore, since I have determined that GABP is a regulator of the mutant TERTp across 16 distinct cancer types, this B1-DN could eventually treat more than a million patients diagnosed with TERT promoter mutant tumors per year. Studies investigating replicating retroviral vectors as a clinically relevant means to deliver the B1-DN are ongoing. In summary, this transgene may be able to reverse tumor cell immortality across all TERTp mutant cancers.

Source coverage

This record comes from a published award list, not a complete project archive. Its abstract comes from CSEF's public project showcase as archived by the Internet Archive before judging (https://web.archive.org/web/20230401224130/https://ca-csef.zfairs.com/showcase/ShowcaseInfo?f=838e60b7-ea75-46e8-865c-fde4864244b3); the version presented may differ.

Awards (1)

  • Category Award: HM

Competition history

  • CSEF 2023 Biochemistry/ Molecular Biology · Entry S0532

Resources

Related projects

Closest projects by meaning, across every fair and year in the corpus.

Browse more like this

Source: California Science & Engineering Fair public projects

Save projects to your library

Sign in with Google to keep track of projects you find interesting, organized into folders. An account also raises your daily allowance for “Has this been done?”, and lets you create a key for the MCP server with a much higher limit than anonymous use. Browsing stays public.

Continue with Google