P63 and P73 Activation in Cancers with p53 Mutation

Cai, Bi-He; Hsu, Yun-Chien; Yeh, Fang-Yu; Lin, Yu-Rou; Lu, Rui-Yu; Yu, Si-Jie; Shaw, Jei‐Fu; Wu, Ming-Han; Tsai, Yi-Zhen; Lin, Ying-Chen; Bai, Zhi-Yu; Shih, Yu-Chen; Hsu, Yi‐Chiang; Liao, Ruo-Yu; Kuo, Wei-Hsin; Hsu, Chao‐Tien; Lien, Chia-Yi; Chen, Chia-Chi

doi:10.3390/biomedicines10071490

Cited by 12 publications

(10 citation statements)

References 162 publications

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“…ΔNp63 is the predominant p63 isoform, which is vital for tumorigenesis and progression and senescence suppression and is associated with poor OS in HNC. [120][121][122] P63 is considered a stem cell marker. 123 Moreover, ΔNp63 affects the growth factor signaling pathway and tumor metabolic microenvironment through hyaluronic acid signaling and a transcriptional program.…”

Section: Mapk Pathwaymentioning

confidence: 99%

Targeted therapy for head and neck cancer: signaling pathways and clinical studies

Tie

Alu

et al. 2023

Sig Transduct Target Ther

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Head and neck cancer (HNC) is malignant, genetically complex and difficult to treat and is the sixth most frequent cancer, with tobacco, alcohol and human papillomavirus being major risk factors. Based on epigenetic data, HNC is remarkably heterogeneous, and treatment remains challenging. There is a lack of significant improvement in survival and quality of life in patients with HNC. Over half of HNC patients experience locoregional recurrence or distal metastasis despite the current multiple traditional therapeutic strategies and immunotherapy. In addition, resistance to chemotherapy, radiotherapy and some targeted therapies is common. Therefore, it is urgent to explore more effective and tolerable targeted therapies to improve the clinical outcomes of HNC patients. Recent targeted therapy studies have focused on identifying promising biomarkers and developing more effective targeted therapies. A well understanding of the pathogenesis of HNC contributes to learning more about its inner association, which provides novel insight into the development of small molecule inhibitors. In this review, we summarized the vital signaling pathways and discussed the current potential therapeutic targets against critical molecules in HNC, as well as presenting preclinical animal models and ongoing or completed clinical studies about targeted therapy, which may contribute to a more favorable prognosis of HNC. Targeted therapy in combination with other therapies and its limitations were also discussed.

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Section: Mapk Pathwaymentioning

confidence: 99%

Targeted therapy for head and neck cancer: signaling pathways and clinical studies

Tie

Alu

et al. 2023

Sig Transduct Target Ther

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“…Either in concert with or as a substitution for p53, p63 and p73 tightly regulate proliferation, metabolic activity, cell differentiation and initiation of apoptosis and/or ferroptosis [ 51 , 53 , 54 , 55 , 56 ]. However, p63 and p73 have a lower mutational rate than p53 [ 57 ].…”

Section: Somatic Mutations In Hcc Pathogenesismentioning

confidence: 99%

Pathogenesis and Current Treatment Strategies of Hepatocellular Carcinoma

et al. 2022

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Hepatocellular carcinoma (HCC) is the most frequent liver cancer with high lethality and low five-year survival rates leading to a substantial worldwide burden for healthcare systems. HCC initiation and progression are favored by different etiological risk factors including hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, non-/and alcoholic fatty liver disease (N/AFLD), and tobacco smoking. In molecular pathogenesis, endogenous alteration in genetics (TP53, TERT, CTNNB1, etc.), epigenetics (DNA-methylation, miRNA, lncRNA, etc.), and dysregulation of key signaling pathways (Wnt/β-catenin, JAK/STAT, etc.) strongly contribute to the development of HCC. The multitude and complexity of different pathomechanisms also reflect the difficulties in tailored medical therapy of HCC. Treatment options for HCC are strictly dependent on tumor staging and liver function, which are structured by the updated Barcelona Clinic Liver Cancer classification system. Surgical resection, local ablative techniques, and liver transplantation are valid and curative therapeutic options for early tumor stages. For multifocal and metastatic diseases, systemic therapy is recommended. While Sorafenib had been the standalone HCC first-line therapy for decades, recent developments had led to the approval of new treatment options as first-line as well as second-line treatment. Anti-PD-L1 directed combination therapies either with anti-VEGF directed agents or with anti-CTLA-4 active substances have been implemented as the new treatment standard in the first-line setting. However, data from clinical trials indicate different responses on specific therapeutic regimens depending on the underlying pathogenesis of hepatocellular cancer. Therefore, histopathological examinations have been re-emphasized by current international clinical guidelines in addition to the standardized radiological diagnosis using contrast-enhanced cross-sectional imaging. In this review, we emphasize the current knowledge on molecular pathogenesis of hepatocellular carcinoma. On this occasion, the treatment sequences for early and advanced tumor stages according to the recently updated Barcelona Clinic Liver Cancer classification system and the current algorithm of systemic therapy (first-, second-, and third-line treatment) are summarized. Furthermore, we discuss novel precautional and pre-therapeutic approaches including therapeutic vaccination, adoptive cell transfer, locoregional therapy enhancement, and non-coding RNA-based therapy as promising treatment options. These novel treatments may prolong overall survival rates in regard with quality of life and liver function as mainstay of HCC therapy.

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“…Indeed, the Vousden and Muller teams demonstrated that mutants p53 can induce a loss of directionality of migration, promote invasion, and interfere with the metastatic behavior [ 30 , 31 ]. The functions of p63 and p73 in the cancer context have been deeply studied [ 8 , 27 , 32 , 33 ]. Regarding p73, several knockdown (KD) in vivo experiments were done to evaluate the role of both TAp73 and ΔNp73 isoforms.…”

Section: P53 Protein Family In Primary Tumors and Metastatic Dissemin...mentioning

confidence: 99%

The p53 Family Members p63 and p73 Roles in the Metastatic Dissemination: Interactions with microRNAs and TGFβ Pathway

Calleja

Lavaud

Tesfaye

et al. 2022

Cancers

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TP53 (TP53), p73 (TP73), and p63 (TP63) are members of the p53 transcription factor family, which has many activities spanning from embryonic development through to tumor suppression. The utilization of two promoters and alternative mRNA splicing has been shown to yield numerous isoforms in p53, p63, and p73. TAp73 is thought to mediate apoptosis as a result of nuclear accumulation following chemotherapy-induced DNA damage, according to a number of studies. Overexpression of the nuclear ΔNp63 and ΔNp73 isoforms, on the other hand, suppresses TAp73’s pro-apoptotic activity in human malignancies, potentially leading to metastatic spread or inhibition. Another well-known pathway that has been associated to metastatic spread is the TGF pathway. TGFs are a family of structurally related polypeptide growth factors that regulate a variety of cellular functions including cell proliferation, lineage determination, differentiation, motility, adhesion, and cell death, making them significant players in development, homeostasis, and wound repair. Various studies have already identified several interactions between the p53 protein family and the TGFb pathway in the context of tumor growth and metastatic spread, beginning to shed light on this enigmatic intricacy.

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P63 and P73 Activation in Cancers with p53 Mutation

Cited by 12 publications

References 162 publications

Targeted therapy for head and neck cancer: signaling pathways and clinical studies

Targeted therapy for head and neck cancer: signaling pathways and clinical studies

Pathogenesis and Current Treatment Strategies of Hepatocellular Carcinoma

The p53 Family Members p63 and p73 Roles in the Metastatic Dissemination: Interactions with microRNAs and TGFβ Pathway

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