Molecular Profile Detail

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Profile Name TP53 mutant
Gene Variant Detail

TP53 mutant (unknown)

Relevant Treatment Approaches

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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
SMARCA4 mut TP53 mut adrenal gland cancer resistant Dabrafenib Preclinical Actionable In a preclinical study, human adrenal gland cancer cells harboring SMARCA4 and TP53 mutations were resistant to Tafinlar (dabrafenib) mediated growth inhibition in culture (PMID: 26343583). 26343583
SMARCA4 mut TP53 mut adrenal gland cancer resistant LY3009120 Preclinical Actionable In a preclinical study, human adrenal gland cancer cells harboring SMARCA4 and TP53 mutations were resistant to LY3009120 mediated growth inhibition in culture (PMID: 26343583). 26343583
SMARCA4 mut TP53 mut adrenal gland cancer resistant Vemurafenib Preclinical Actionable In a preclinical study, human adrenal gland cancer cells harboring SMARCA4 and TP53 mutations were resistant to Zelboraf (vemurafenib) mediated growth inhibition in culture (PMID: 26343583). 26343583
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