p53 as an Effector or Inhibitor of Therapy Response

Ablain, Julien; Poirot, Brigitte; Esnault, Cécile; Lehmann-Che, Jacqueline

doi:10.1101/cshperspect.a026260

Cited by 11 publications

(9 citation statements)

References 88 publications

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“…Other cell types may be susceptible to different cellular stresses and respond in a similar manner by activating HEXIM1 to help the cell repair or induce cell death. Finding such dependencies in other cancers could lead to the development of new cancer therapies using the zebrafish model ( Figure 3 ) [ 62 , 95 ].…”

Section: Compounds and Inhibitors For Melanoma Treatmentmentioning

confidence: 99%

Zebrafish as a Model Organism for the Development of Drugs for Skin Cancer

Bootorabi

Manouchehri

Changizi

et al. 2017

IJMS

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Skin cancer, which includes melanoma and squamous cell carcinoma, represents the most common type of cutaneous malignancy worldwide, and its incidence is expected to rise in the near future. This condition derives from acquired genetic dysregulation of signaling pathways involved in the proliferation and apoptosis of skin cells. The development of animal models has allowed a better understanding of these pathomechanisms, with the possibility of carrying out toxicological screening and drug development. In particular, the zebrafish (Danio rerio) has been established as one of the most important model organisms for cancer research. This model is particularly suitable for live cell imaging and high-throughput drug screening in a large-scale fashion. Thanks to the recent advances in genome editing, such as the clustered regularly-interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) methodologies, the mechanisms associated with cancer development and progression, as well as drug resistance can be investigated and comprehended. With these unique tools, the zebrafish represents a powerful platform for skin cancer research in the development of target therapies. Here, we will review the advantages of using the zebrafish model for drug discovery and toxicological and phenotypical screening. We will focus in detail on the most recent progress in the field of zebrafish model generation for the study of melanoma and squamous cell carcinoma (SCC), including cancer cell injection and transgenic animal development. Moreover, we will report the latest compounds and small molecules under investigation in melanoma zebrafish models.

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Section: Compounds and Inhibitors For Melanoma Treatmentmentioning

confidence: 99%

Zebrafish as a Model Organism for the Development of Drugs for Skin Cancer

Bootorabi

Manouchehri

Changizi

et al. 2017

IJMS

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“…It has been demonstrated that mutations in p53 or loss of p53 function are associated with multidrug resistance in many tumors (7). Moreover, it was recently shown that p53 may act both as an effector and as an inhibitor of dose-dense chemotherapy depending on the type of tumor under treatment (8). It is clear that the reasons, not only for the specific properties of each different type of tumor population, but also regarding the changes of the factors that interfere with the downstream regulation of the activated p53 pathway should be sought.…”

mentioning

confidence: 99%

The Prognostic Value of the Immunohistochemical Expression of Phosphorylated RB and p16 Proteins in Association with Cyclin D1 and the p53 Pathway in a Large Cohort of Patients with Breast Cancer Treated with Taxane-based Adjuvant Chemotherapy

Gavressea

Kalogeras

Koliou

et al. 2017

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“…It is known that TP53 is frequently altered in the majority of human cancers . Along with TP53 alterations, breast cancers were more sensitive to DNA‐damaging therapy because of loss of p53‐dependent transcriptional control . We found that TP53 was altered in 61.2% of cases and it had higher alteration rates in HR−HER2− tumors (Table ).…”

Section: Discussionmentioning

confidence: 70%

“…25 Along with TP53 alterations, breast cancers were more sensitive to DNA-damaging therapy because of loss of p53dependent transcriptional control. 26 We found that TP53 was altered in 61.2% of cases and it had higher alteration rates in HR−HER2− tumors (Table S2). For breast cancers that harbored TP53 mutation, it was easier to reach pCR (Table 2).…”

Section: Discussionmentioning

confidence: 83%

Somatic alterations of TP53, ERBB2, PIK3CA and CCND1 are associated with chemosensitivity for breast cancers

Yang

Bao

et al. 2019

Cancer Science

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The correlation of genetic alterations with response to neoadjuvant chemotherapy (NAC) has not been fully revealed. In this study, we enrolled 247 breast cancer patients receiving anthracycline‐taxane‐based NAC treatment. A next generation sequencing (NGS) panel containing 36 hotspot breast cancer‐related genes was used in this study. Two different standards for the extent of pathologic complete response (pCR), ypT0/isypN0 and ypT0/is, were used as indicators for NAC treatment. TP53 mutation (n = 149, 60.3%), PIK3CA mutation (n = 109, 44.1%) and MYC amplification (n = 95, 38.5%) were frequently detected in enrolled cases. TP53 mutation ( P = 0.019 for ypT0/isypN0 and P = 0.003 for ypT0/is) and ERBB2 amplification ( P < 0.001 for both ypT0/isypN0 and ypT0/is) were related to higher pCR rates. PIK3CA mutation ( P = 0.040 for ypT0/isypN0) and CCND2 amplification ( P = 0.042 for ypT0/is) showed reduced sensitivity to NAC. Patients with MAPK pathway alteration had low pCR rates ( P = 0.043 for ypT0/is). Patients with TP53 mutation (−) PIK3CA mutation (−) ERBB2 amplification (+) CCND1 amplification (−), TP53 mutation (+) PIK3CA mutation (−) ERBB2 amplification (+) CCND1 amplification (−) or TP53 mutation (+) PIK3CA mutation (+) ERBB2 amplification (+) CCND1 amplification (−)had significantly higher pCR rates ( P < 0.05 for ypT0/isypN0 and ypT0/is) than wild type genotype tumors. Some cancer genetic alterations as well as pathway alterations were associated with chemosensitivity to NAC treatment. Our study may shed light on the molecular characteristics of breast cancer for prediction of NAC expectations when breast cancer is first diagnosed by biopsy.

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p53 as an Effector or Inhibitor of Therapy Response

Cited by 11 publications

References 88 publications

Zebrafish as a Model Organism for the Development of Drugs for Skin Cancer

Zebrafish as a Model Organism for the Development of Drugs for Skin Cancer

The Prognostic Value of the Immunohistochemical Expression of Phosphorylated RB and p16 Proteins in Association with Cyclin D1 and the p53 Pathway in a Large Cohort of Patients with Breast Cancer Treated with Taxane-based Adjuvant Chemotherapy

Somatic alterations of TP53, ERBB2, PIK3CA and CCND1 are associated with chemosensitivity for breast cancers

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