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| Gene | TP53 |
| Variant | loss |
| Impact List | unknown |
| Protein Effect | loss of function |
| Gene Variant Descriptions | TP53 loss indicates loss of the TP53 gene, mRNA, and protein. |
| Associated Drug Resistance | |
| Category Variants Paths |
TP53 mutant TP53 inact mut TP53 loss |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| TP53 loss | chronic lymphocytic leukemia/small lymphocytic lymphoma | 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 | 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 | 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 | chronic lymphocytic leukemia/small lymphocytic lymphoma | 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 | chronic lymphocytic leukemia/small lymphocytic lymphoma | 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 | 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 | 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 | chronic lymphocytic leukemia/small lymphocytic lymphoma | 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 | chronic lymphocytic leukemia/small lymphocytic lymphoma | 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 | chronic lymphocytic leukemia/small lymphocytic lymphoma | 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 | 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 | chronic lymphocytic leukemia/small lymphocytic lymphoma | 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 | 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 | chronic lymphocytic leukemia/small lymphocytic lymphoma | 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 | chronic lymphocytic leukemia/small lymphocytic lymphoma | 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 | 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 | 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 | 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 | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Ibrutinib + Venetoclax | Guideline | Actionable | Venclexta (venetoclax) combined with Imbruvica (ibrutinib) is indicated in guidelines as first-line (category 2A), second-line, or third-line therapy (category 2B) 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 | 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 | chronic lymphocytic leukemia/small lymphocytic lymphoma | 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 | 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 | 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 | 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 | chronic lymphocytic leukemia/small lymphocytic lymphoma | 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 | 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 | 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 | chronic lymphocytic leukemia/small lymphocytic lymphoma | 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 | 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 | 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 | 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 | 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 | chronic lymphocytic leukemia/small lymphocytic lymphoma | 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 | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Pirtobrutinib | Guideline | Actionable | Jaypirca (pirtobrutinib) is included in guidelines as second-line or third-line therapy for patients with chronic lymphocytic leukemia/small lymphocytic lymphoma with TP53 loss and for patients with relapsed or refractory disease after prior BTK inhibitor and Venclexta (venetoclax)-based therapy (NCCN.org). | detail... |
| TP53 loss | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Alemtuzumab + Rituximab | Guideline | Actionable | Campath (alemtuzumab) combined with Rituxan (rituximab) is indicated in guidelines as therapy for patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with TP53 loss who received prior treatment with a BTK inhibitor or Venclexta (venetoclax)-based therapy (NCCN.org). | detail... |
| TP53 loss | chronic lymphocytic leukemia/small lymphocytic lymphoma | 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 | chronic lymphocytic leukemia/small lymphocytic lymphoma | sensitive | Methylprednisolone + Obinutuzumab | Guideline | Actionable | Artisone-Wyeth (methylprednisolone) combined with Gazyva (obinutuzumab) is indicated in guidelines as first-line therapy for chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TP53 loss and for patients with relapsed or refractory disease after prior BTK inhibitor or Venclexta (venetoclax)-based therapy (NCCN.org). | detail... |