The Development of p53-Targeted Therapies for Human Cancers

Lu, Yun-Bi; Wu, Meng; Xu, Yang; Yu, Lili

doi:10.3390/cancers15143560

Cited by 13 publications

(7 citation statements)

References 115 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…After study selection, 77 studies [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 ,…”

Section: Resultsunclassified

“…Unlike some other proteins with well-defined drug binding sites, p53 lacks such druggable pockets. It has a relatively flat and featureless surface, making it challenging to design small molecules that can effectively bind and modulate p53’s activity [ 61 ].…”

Section: Resultsmentioning

confidence: 99%

“…MDM2 can negatively regulate the stability and activity of wtp53. Several MDM2 inhibitors have been studied in pre-clinical tests to act against malignant cells [ 61 ]. Nutlin-3 was the first drug to disrupt the interaction between p53 and MDM2 [ 62 ].…”

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Molecular Profile of Intrahepatic Cholangiocarcinoma

Andraus,

Tustumi,

de Meira Junior

et al. 2023

IJMS

View full text Add to dashboard Cite

Intrahepatic cholangiocarcinoma (ICC) is a relatively uncommon but highly aggressive primary liver cancer that originates within the liver. The aim of this study is to review the molecular profile of intrahepatic cholangiocarcinoma and its implications for prognostication and decision-making. This comprehensive characterization of ICC tumors sheds light on the disease’s underlying biology and offers a foundation for more personalized treatment strategies. This is a narrative review of the prognostic and therapeutic role of the molecular profile of ICC. Knowing the molecular profile of tumors helps determine prognosis and support certain target therapies. The molecular panel in ICC helps to select patients for specific therapies, predict treatment responses, and monitor treatment responses. Precision medicine in ICC can promote improvement in prognosis and reduce unnecessary toxicity and might have a significant role in the management of ICC in the following years. The main mutations in ICC are in tumor protein p53 (TP53), Kirsten rat sarcoma virus (KRAS), isocitrate dehydrogenase 1 (IDH1), and AT-rich interactive domain-containing protein 1A (ARID1A). The rate of mutations varies significantly for each population. Targeting TP53 and KRAS is challenging due to the natural characteristics of these genes. Different stages of clinical studies have shown encouraging results with inhibitors of mutated IDH1 and target therapy for ARID1A downstream effectors. Fibroblast growth factor receptor 2 (FGFR2) fusions are an important target in patients with ICC. Immune checkpoint blockade can be applied to a small percentage of ICC patients. Molecular profiling in ICC represents a groundbreaking approach to understanding and managing this complex liver cancer. As our comprehension of ICC’s molecular intricacies continues to expand, so does the potential for offering patients more precise and effective treatments. The integration of molecular profiling into clinical practice signifies the dawn of a new era in ICC care, emphasizing personalized medicine in the ongoing battle against this malignancy.

show abstract

Section: Resultsunclassified

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Molecular Profile of Intrahepatic Cholangiocarcinoma

Andraus,

Tustumi,

de Meira Junior

et al. 2023

IJMS

View full text Add to dashboard Cite

show abstract

“…Current research is thus focused on restoring the normal anti-cancer function of p53 in both wtp53 and mutp53 cells. This includes developing molecules to disrupt the wtp53-MDM2/MDM4 interaction in wtp53-expressing cancers and reinstating wtp53-like functions in mutp53-expressing cancers [165]. Unlike genetic mutations, the active regulation of protein might provide new insights for assessing MPC risk, particularly in patients with wtp53.…”

Section: Multifocal Esophageal Cancersmentioning

confidence: 99%

Susceptibility Genes Associated with Multiple Primary Cancers

Lu,

Zhang,

Chu

et al. 2023

Cancers

View full text Add to dashboard Cite

With advancements in treatment and screening techniques, we have been witnessing an era where more cancer survivors harbor multiple primary cancers (MPCs), affecting approximately one in six patients. Identifying MPCs is crucial for tumor staging and subsequent treatment choices. However, the current clinicopathological criteria for clinical application are limited and insufficient, making it challenging to differentiate them from recurrences or metastases. The emergence of next-generation sequencing (NGS) technology has provided a genetic perspective for defining multiple primary cancers. Researchers have found that, when considering multiple tumor pairs, it is crucial not only to examine well-known essential mutations like MLH1/MSH2, EGFR, PTEN, BRCA1/2, CHEK2, and TP53 mutations but also to explore certain pleiotropic loci. Moreover, specific deleterious mutations may serve as regulatory factors in second cancer development following treatment. This review aims to discuss these susceptibility genes and provide an explanation of their functions based on the signaling pathway background. Additionally, the association network between genetic signatures and different tumor pairs will be summarized.

show abstract

“…Elevated levels of structurally unstable proteins contribute to the genetic instability and continuous proliferation observed in cancer cells[ 15 ]. Additionally, cancer cells experience heightened metabolism and protein synthesis, leading to a persistent state of cellular stress that must be counterbalanced[ 16 , 17 ]. As a result, tumor cells heavily rely on the maintenance of protein homeostasis through molecular chaperones.…”

Section: Introductionmentioning

confidence: 99%

Prognostic and immunological roles of heat shock protein A4 in lung adenocarcinoma

Wu,

Yang,

Zhang

et al. 2024

World J Clin Oncol

View full text Add to dashboard Cite

BACKGROUND Heat shock protein A4 (HSPA4) belongs to molecular chaperone protein family which plays important roles within variable cellular activities, including cancer initiation and progression. However, the prognostic and immunological significance of HSPA4 in lung adenocarcinoma (LUAD) has not been revealed yet. AIM To explore the prognostic and immunological roles of HSPA4 to identify a novel prognostic biomarker and therapeutic target for LUAD. METHODS We assessed the prognostic and immunological significance of HSPA4 in LUAD using data from The Cancer Genome Atlas database. The association between HSPA4 expression and clinical-pathological features was assessed through Kruskal-Wallis and Wilcoxon signed-rank test. Univariate/multivariate Cox regression analyses and Kaplan-Meier curves were employed to evaluate prognostic factors, including HSPA4, in LUAD. Gene set enrichment analysis (GSEA) was conducted to identify the key signaling pathways associated with HSPA4. The correlation between HSPA4 expression and cancer immune infiltration was evaluated using single-sample gene set enrichment analysis (ssGSEA). RESULTS Overexpressing HSPA4 was significantly related to advanced pathologic TNM stage, advanced pathologic stage, progression disease status of primary therapy outcome and female subgroups with LUAD. In addition, increased HSPA4 expression was found to be related to worse disease-specific survival and overall survival. GSEA analysis indicated a significant correlation between HSPA4 and cell cycle regulation and immune response, particularly through diminishing the function of cytotoxicity cells and CD8 T cells. The ssGSEA algorithm showed a positive correlation between HSPA4 expression and infiltrating levels of Th2 cells, while a negative correlation was observed with cytotoxic cell infiltration levels. CONCLUSION Our findings indicate HSPA4 is related to prognosis and immune cell infiltrates and may act as a novel prognostic biomarker and therapeutic target for LUAD.

show abstract

The Development of p53-Targeted Therapies for Human Cancers

Cited by 13 publications

References 115 publications

Molecular Profile of Intrahepatic Cholangiocarcinoma

Molecular Profile of Intrahepatic Cholangiocarcinoma

Susceptibility Genes Associated with Multiple Primary Cancers

Prognostic and immunological roles of heat shock protein A4 in lung adenocarcinoma

Contact Info

Product

Resources

About