Missing content? – Request curation!
Request curation for specific Genes, Variants, or PubMed publications.
Have questions, comments, or suggestions? - Let us know!
Email us at : ckbsupport@jax.org
Profile Name | TP53 mutant |
Gene Variant Detail | |
Relevant Treatment Approaches |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
PTEN mut TP53 mut | skin cancer | sensitive | Sapanisertib | Preclinical | Actionable | In a preclinical study, a skin cancer cell line harboring mutations in PTEN and TP53 demonstrated sensitivity to Sapanisertib (MLN0128) in culture (PMID: 25261369). | 25261369 |
RB1 mut TP53 mut | breast carcinoma | sensitive | R547 | Preclinical | Actionable | In a preclinical study, R547 inhibited proliferation of breast carcinoma cell lines harboring TP53 and RB1 mutations in culture (PMID: 17121911). | 17121911 |
RB1 wild-type TP53 mut | breast carcinoma | sensitive | R547 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, R547 inhibited proliferation of breast carcinoma cell lines harboring mutant Tp53 and wild-type Rb1 in culture and reduced tumor growth in xenograft models (PMID: 17121911). | 17121911 |
RB1 wild-type TP53 mut | colon carcinoma | sensitive | R547 | Preclinical | Actionable | In a preclinical study, R547 inhibited proliferation of colon carcinoma cell lines harboring mutant Tp53 and wild-type Rb1 (PMID: 17121911). | 17121911 |
RB1 mut TP53 mut | cervical cancer | sensitive | R547 | Preclinical | Actionable | In a preclinical study, R547 inhibited proliferation of cervical carcinoma cell lines harboring Tp53 and Rb1 mutations (PMID: 17121911). | 17121911 |
RB1 mut TP53 mut | prostate carcinoma | sensitive | R547 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, R547 inhibited proliferation of prostate carcinoma cell lines harboring Tp53 and Rb1 mutations in culture and reduced tumor growth in xenograft models (PMID: 17121911). | 17121911 |
RB1 wild-type TP53 mut | osteosarcoma | sensitive | R547 | Preclinical | Actionable | In a preclinical study, R547 inhibited proliferation of osteosarcoma cell lines harboring mutant Tp53 and wild-type Rb1 (PMID: 17121911). | 17121911 |
RB1 wild-type TP53 mut | mantle cell lymphoma | sensitive | R547 | Preclinical | Actionable | In a preclinical study, R547 inhibited proliferation of mantle cell lymphoma cell lines harboring mutant Tp53 and wild-type Rb1 (PMID: 17121911). | 17121911 |
ALK wild-type TP53 mut | neuroblastoma | no benefit | Crizotinib + Cyclophosphamide + Topotecan | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) did not demonstrate synergy with the combination of Topotecan and Cytoxan (cyclophosphamide) on growth inhibition in neuroblastoma cell lines harboring wild-tpye Alk and TP53 mutations in culture (PMID: 26438783). | 26438783 |
PTEN mut TP53 mut | glioblastoma | sensitive | Navitoclax + ONC201 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of ONC201 (TIC10) and Navitoclax (ABT-263) increased apoptosis and worked synergistically to inhibit proliferation of a glioblastoma cell line harboring mutations in PTEN and TP53 in culture (PMID: 26474387). | 26474387 |
BRAF mut TP53 mut | colorectal cancer | sensitive | Alpelisib + Dabrafenib + Erlotinib + Navitoclax | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Navitoclax (ABT-263), Alpelisib (BYL719), Tafinlar (dabrafenib), and Tarceva (erlotinib) resulted in the greatest synergistic effect and inhibition of cell growth in colorectal cancer cells harboring a BRAF mutation and TP53 mutation in culture compared to the double or triple combinations of the therapies (PMID: 27659046). | 27659046 |
ALK rearrange TP53 mut | lung non-small cell carcinoma | decreased response | Crizotinib | Clinical Study - Cohort | Actionable | In a clinical study, TP53 mutant ALK-rearranged non-small cell lung cancer patients demonstrated a lower median progression-free survival following treatment with Xalkori (crizotinib) as a first line therapy or after chemotherapy vs. patients with wild-type TP53 (5.0 mo., n=22 vs. 14.0 mo., n=71; p<0.001), and a lower median overall survival (17.0 mo., n=13 vs. not reached n=50; p=0.049) (PMID: 30165392). | 30165392 |
ALK rearrange TP53 mut | lung non-small cell carcinoma | decreased response | Ceritinib | Clinical Study - Cohort | Actionable | In a clinical study, TP53 mutant ALK-rearranged non-small cell lung cancer patients demonstrated a lower median progression-free survival following treatment with Zykadia (ceritinib), Alecensa (alectinib), or Alunbrig (brigatinib) after Xalkori (crizotinib) vs. patients with wild-type TP53 (5.4 mo. vs. 9.9 mo.; p=0.039), and a lower median overall survival with treatment with Zykadia (ceritinib) after Xalkori (crizotinib) of 7.0 mo. vs. 50.0 mo. in patients with wild-type TP53 (p=0.001) (PMID: 30165392). | 30165392 |
ALK rearrange TP53 mut | lung non-small cell carcinoma | decreased response | Alectinib | Clinical Study - Cohort | Actionable | In a clinical study, TP53 mutant ALK-rearranged non-small cell lung cancer patients demonstrated a lower median progression-free survival following treatment with Zykadia (ceritinib), Alecensa (alectinib), or Alunbrig (brigatinib) after Xalkori (crizotinib) vs. patients with wild-type TP53 (5.4 mo. vs. 9.9 mo.; p=0.039) (PMID: 30165392). | 30165392 |
ALK rearrange TP53 mut | lung non-small cell carcinoma | decreased response | Brigatinib | Clinical Study - Cohort | Actionable | In a clinical study, TP53 mutant ALK-rearranged non-small cell lung cancer patients demonstrated a lower median progression-free survival following treatment with Zykadia (ceritinib), Alecensa (alectinib), or Alunbrig (brigatinib) after Xalkori (crizotinib) vs. patients with wild-type TP53 (5.4 mo. vs. 9.9 mo.; p=0.039) (PMID: 30165392). | 30165392 |
ROS1 rearrange TP53 mut | lung non-small cell carcinoma | predicted - sensitive | Crizotinib | Clinical Study - Cohort | Actionable | In a Phase II clinical trial, treatment with Xalkori (crizotinib) demonstrated a shorter median progression-free survival in patients with non-small cell lung cancer co-harboring a ROS1 rearrangement and TP53 mutation compared to patients with a ROS1 rearrangement and wild-type TP53 (7 vs. 24.1 months; p=0.022) (PMID: 30978502; NCT02183870). | 30978502 |
NRAS mut TP53 mut | colorectal cancer | no benefit | Adavosertib | Phase II | Actionable | In a Phase II trial (FOCUS4-C), Adavosertib (AZD1775) treatment was well-tolerated and resulted in an advantage in progression-free survival (PFS, HR 0.40, p=0.0051) but not overall survival (0.92, p=0.93) compared to active monitoring in patients with metastatic colorectal cancer harboring both RAS and TP53 mutations, however, patients with NRAS mutations or KRAS non-G12/G13 mutations did not benefit from Adavosertib (AZD1775) treatment in subgroup PFS analysis (PMID: 34538072). | 34538072 |