Molecular Profile Detail

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Profile Name TP53 loss
Gene Variant Detail

TP53 loss (loss of function)

Relevant Treatment Approaches

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
TP53 loss CLL/SLL sensitive Obinutuzumab + Venetoclax Guideline Actionable The combination of Venclexta (venetoclax) and Gazyva (obinutuzumab) is indicated in the guidelines as first line therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org). detail...
TP53 loss colon carcinoma sensitive SP600125 Preclinical Actionable In a preclinical study, SP600125 induced cell death in colon carcinoma cells deficient for p53 (PMID: 22438244). 22438244
TP53 loss colorectal cancer predicted - sensitive Ad5CMV-p53 gene Preclinical Actionable In a preclinical study, Ad5CMV-p53 gene therapy suppressed growth of allograft colorectal cancer in rat models (PMID: 15608394). 15608394
TP53 loss colon carcinoma sensitive MPI-0479605 Preclinical Actionable In a preclinical study the TTK (MPS1) inhibitor, MPI-0479605, inhibited cell cycle progression of colon carcinoma cells deficient for Tp53 with equivalent efficacy to cells with wild-type Tp53 (PMID: 21980130). 21980130
TP53 loss CLL/SLL sensitive Acalabrutinib + Obinutuzumab Guideline Actionable Calquence (acalabrutinib) combined with Gazyva (obinutuzumab) is indicated in the guidelines as first-line therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org). detail...
TP53 loss mantle cell lymphoma predicted - sensitive Ibrutinib + Rituximab Case Reports/Case Series Actionable In a clinical case study, a patient with non-nodal leukemic mantle cell lymphoma with TP53 loss, as well as a CCND1 translocation, had a rapid response to combined Rituxan (rituximab) and Imbruvica (ibrutinib) therapy, achieved a complete remission (CR) within 6 months, underwent autologous stem-cell transplantation, and remained in CR 18 months thereafter (PMID: 30559058). 30559058
TP53 loss colorectal cancer sensitive PHA-680632 + Radiotherapy Preclinical - Pdx Actionable In a preclinical study, PHA-680632 synergized with radiotherapy to decrease tumor growth in Pdx models deficient in Tp53 (PMID: 18026198). 18026198
TP53 loss ovarian cancer sensitive Cisplatin + LB-100 Preclinical Actionable In a preclinical study, LB100 treatment decreased PP2A activity and increased sensitivity to Platinol (cisplatin) in cisplatin-resistant ovarian cancer cells with TP53 loss in culture and in xenograft models (PMID: 25376608). 25376608
TP53 loss thymoma predicted - resistant Selinexor Preclinical - Cell culture Actionable In a preclinical study, a thymoma cell line with TP53 loss demonstrated primary resistance to Selinexor (KPT-330) in culture, and reconstitution of TP53 expression resulted in increased Selinexor sensitivity (PMID: 28819023). 28819023
TP53 loss osteosarcoma decreased response CPUY201112 Preclinical Actionable In a preclinical study, an osteosarcoma cell line lacking TP53 demonstrated a decreased response to CPUY201112 in culture, when compared to osteosarcoma cells with wild-type TP53 (PMID: 26743233). 26743233
TP53 loss CLL/SLL sensitive Venetoclax Guideline Actionable Venclexta (venetoclax) is indicated in the guidelines as second line and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org). detail...
TP53 loss CLL/SLL sensitive Lenalidomide + Rituximab Guideline Actionable Revlimid (lenalidomide) combined with Rituxan (rituximab) is indicated in the guidelines as second line and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org). detail...
TP53 loss lung cancer resistant KRT-232 Preclinical - Cell culture Actionable In a preclinical study, TP53-null lung cancer cells were resistant to KRT-232 (AMG 232) induced growth inhibition in culture (PMID: 26162687). 26162687
TP53 loss colon cancer sensitive CHIR-124 + SN-38 Preclinical - Cell culture Actionable In a preclinical study, a colon cancer cell line deficient in TP53 demonstrated increased sensitivity to sequential treatment with SN-38 and CHIR-124 compared to cells with wild-type TP53, resulting in increased apoptosis and micronucleation in culture (PMID: 17255282). 17255282
TP53 loss CLL/SLL sensitive Ofatumumab Guideline Actionable Arzerra (ofatumumab) is indicated in the guidelines as second line and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org). detail...
TP53 loss colon cancer decreased response CPUY201112 Preclinical Actionable In a preclinical study, colon cancer cells lacking TP53 had a decreased response to CPUY201112 in culture, when compared to colon cancer cells with wild-type TP53 (PMID: 26743233). 26743233
TP53 loss pancreatic cancer sensitive Adavosertib + Gemcitabine Preclinical - Pdx Actionable In a preclinical study, the combination of Adavosertib (MK-1775) and Gemzar (gemcitabine) inhibited Wee1 expression, Cdc2 phosphorylation, and tumor growth in several patient-derived xenograft models of pancreatic cancer harboring TP53 mutations (PMID: 21389100). 21389100
TP53 loss CLL/SLL sensitive Idelalisib + Rituximab Guideline Actionable Zydelig (idelalisib) combined with Rituxan (rituximab) is indicated in the guidelines as second line and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org). detail...
TP53 loss glioblastoma sensitive BLZ945 Preclinical Actionable In a preclinical study, treatment with BLZ945 demonstrated some efficacy, specifically a 56% tumor reduction, in transgenic mouse models of glioblastoma with a loss of TP53 (PMID: 27199435). 27199435
TP53 loss CLL/SLL sensitive Obinutuzumab Guideline Actionable Gazyva (obinutuzumab) is indicated in the guidelines as first line therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org). detail...
TP53 loss CLL/SLL sensitive Duvelisib Guideline Actionable Copiktra (duvelisib) is indicated in the guidelines as second line and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org). detail...
TP53 loss CLL/SLL sensitive Zanubrutinib Guideline Actionable Brukinsa (zanubrutinib) is included in guidelines as first line therapy and second line therapy and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org). detail...
TP53 loss mantle cell lymphoma no benefit Bendamustine + Rituximab Case Reports/Case Series Actionable In a clinical case study, a patient with non-nodal leukemic mantle cell lymphoma with TP53 loss, as well as a CCND1 translocation, had no response to combined Rituxan (rituximab) and Treanda (bendamustine) therapy, and had a doubling of white blood cells during two cycles of treatment (PMID: 30559058). 30559058
TP53 loss lung cancer resistant KRT-232 + Radiotherapy Preclinical - Cell line xenograft Actionable In a preclinical study, KRT-232 (AMG 232) did not enhance radiation-induced cytotoxicity in TP53-null lung cancer cells in culture and in cell line xenograft models (PMID: 26162687). 26162687
TP53 loss Advanced Solid Tumor sensitive Adavosertib Preclinical Actionable In a preclinical study, tumor cell lines carrying deficient TP53 were sensitized to DNA-damaging agents upon Adavosertib (MK-1775) administration (PMID: 19887545). 19887545
TP53 loss CLL/SLL not applicable N/A Guideline Prognostic Loss of TP53 is associated with a poor prognosis in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (NCCN.org). detail...
TP53 loss acute myeloid leukemia resistant ALRN-6924 Preclinical - Cell culture Actionable In a preclinical study, ALRN-6924 did not inhibit the growth of TP53-null acute myeloid leukemia cells in culture (PMID: 29643228). 29643228
TP53 loss colorectal cancer sensitive Ceralasertib + Radiotherapy Preclinical - Cell line xenograft Actionable In a preclinical study, AZD6738 increased sensitivity to radiotherapy in colorectal cancer xenograft models harboring a loss of TP53, resulting in a greater delay of tumor growth compared to radiation alone and an improved survival compared to control or either agent alone (PMID: 28062704). 28062704
TP53 loss colorectal cancer sensitive Prodigiosin Preclinical Actionable In a preclinical study, Prodigiosin inhibited self-renewal of colorectal cancer cell lines harboring TP53 loss in culture (PMID: 26759239). 26759239
TP53 loss CLL/SLL sensitive Acalabrutinib Guideline Actionable Calquence (acalabrutinib) is indicated in the guidelines as second line and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org). detail...
TP53 loss Advanced Solid Tumor decreased response CTX-1 Preclinical Actionable In a preclinical study, CTX-1 induced cell death in TP53-deficient human tumor cell lines in culture, but had a greater effect on cell lines with wild-type TP53 compared to isogenic cell lines with TP53 loss (PMID: 26883273). 26883273
TP53 loss CLL/SLL sensitive Rituximab + Venetoclax Guideline Actionable Venclexta (venetoclax) combined with Rituxan (rituximab) is indicated in the guidelines as second line and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org). detail...
TP53 loss CLL/SLL sensitive Methylprednisolone + Rituximab Guideline Actionable Artisone-Wyeth (methylprednisolone) combined with Rituxan (rituximab) is indicated in the guidelines as first-line therapy and second line and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org). detail...
TP53 loss CLL/SLL sensitive Ibrutinib Guideline Actionable Imbruvica (ibrutinib) is indicated in the guidelines as first line therapy and second line and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org). detail...
TP53 loss ovarian cancer no benefit ReACp53 Preclinical Actionable In a preclincial study, ReACp53 did not induce cell death in ovarian cancer cells with loss of TP53 in culture (PMID: 26748848). 26748848
TP53 loss CLL/SLL sensitive Idelalisib Guideline Actionable Zydelig (idelalisib) is indicated in the guidelines as second line and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org). detail...
TP53 loss CLL/SLL sensitive Alemtuzumab + Rituximab Guideline Actionable Campath (alemtuzumab) combined with Rituxan (rituximab) is indicated in the guidelines as first-line therapy and second line and subsequent therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss (NCCN.org). detail...
Clinical Trial Phase Therapies Title Recruitment Status Covered Countries Other Countries
NCT02612285 Phase II SNX-5422 Study of SNX-5422 in TP53 Null Cancers Terminated USA 0
NCT04388852 Phase I DS-3201b + Ipilimumab DS3201 and Ipilimumab for the Treatment of Metastatic Prostate, Urothelial and Renal Cell Cancers Recruiting USA 0
NCT04592237 Phase II Niraparib Cabazitaxel + Carboplatin + JNJ-63723283 JNJ-63723283 + Niraparib Cabazitaxel, Carboplatin, and Cetrelimab Followed by Niraparib With or Without Cetrelimab for the Treatment of Aggressive Variant Metastatic Prostate Cancer Recruiting USA 0