Side-stepping the guardian of the genome: current cancer therapeutics targeting mutant p53
Cancer therapies have attempted to target the transcription factor p53, a gene also described as the “guardian of the genome,” for decades. However, the approach has faced numerous barriers to clinical efficacy due to several factors: mutations in p53 occur in almost half of all human cancers, mutat...
Saved in:
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-01-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1529483/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832582964636024832 |
|---|---|
| author | Iulianna C. Taritsa Eric T. Fossel |
| author_facet | Iulianna C. Taritsa Eric T. Fossel |
| author_sort | Iulianna C. Taritsa |
| collection | DOAJ |
| description | Cancer therapies have attempted to target the transcription factor p53, a gene also described as the “guardian of the genome,” for decades. However, the approach has faced numerous barriers to clinical efficacy due to several factors: mutations in p53 occur in almost half of all human cancers, mutations are cancer-specific, and the associated genomic changes grant mutant p53 with oncogenic potential unique from that of wild-type p53. A host of new therapeutic agents have emerged that work to target mutant p53. These agents can broadly be classified into six categories: the viral approach, direct modifiers of the p53 pathway, epigenetic modifiers of the p53 pathway, synthetic lethal agents, structural reactivators, and immune activating vaccines. Even these strategies have been met with limited success. Bypassing p53 entirely may be the next avenue in cancer therapeutics to kill tumor cells regardless of p53’s mutation pattern. |
| format | Article |
| id | doaj-art-9b0b7597e82749eea039de731f3534dc |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-9b0b7597e82749eea039de731f3534dc2025-01-29T06:45:32ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-01-011610.3389/fphar.2025.15294831529483Side-stepping the guardian of the genome: current cancer therapeutics targeting mutant p53Iulianna C. TaritsaEric T. FosselCancer therapies have attempted to target the transcription factor p53, a gene also described as the “guardian of the genome,” for decades. However, the approach has faced numerous barriers to clinical efficacy due to several factors: mutations in p53 occur in almost half of all human cancers, mutations are cancer-specific, and the associated genomic changes grant mutant p53 with oncogenic potential unique from that of wild-type p53. A host of new therapeutic agents have emerged that work to target mutant p53. These agents can broadly be classified into six categories: the viral approach, direct modifiers of the p53 pathway, epigenetic modifiers of the p53 pathway, synthetic lethal agents, structural reactivators, and immune activating vaccines. Even these strategies have been met with limited success. Bypassing p53 entirely may be the next avenue in cancer therapeutics to kill tumor cells regardless of p53’s mutation pattern.https://www.frontiersin.org/articles/10.3389/fphar.2025.1529483/fulloncologyp53immuno oncologytherapeuticscancerimmunogenic cell death |
| spellingShingle | Iulianna C. Taritsa Eric T. Fossel Side-stepping the guardian of the genome: current cancer therapeutics targeting mutant p53 Frontiers in Pharmacology oncology p53 immuno oncology therapeutics cancer immunogenic cell death |
| title | Side-stepping the guardian of the genome: current cancer therapeutics targeting mutant p53 |
| title_full | Side-stepping the guardian of the genome: current cancer therapeutics targeting mutant p53 |
| title_fullStr | Side-stepping the guardian of the genome: current cancer therapeutics targeting mutant p53 |
| title_full_unstemmed | Side-stepping the guardian of the genome: current cancer therapeutics targeting mutant p53 |
| title_short | Side-stepping the guardian of the genome: current cancer therapeutics targeting mutant p53 |
| title_sort | side stepping the guardian of the genome current cancer therapeutics targeting mutant p53 |
| topic | oncology p53 immuno oncology therapeutics cancer immunogenic cell death |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1529483/full |
| work_keys_str_mv | AT iuliannactaritsa sidesteppingtheguardianofthegenomecurrentcancertherapeuticstargetingmutantp53 AT erictfossel sidesteppingtheguardianofthegenomecurrentcancertherapeuticstargetingmutantp53 |