p53 as a potential target for treatment of cancer: A perspective on recent advancements in small molecules with structural insights and SAR studies

Chahat, None; Bhatia, Rohit; Kumar, Bhupinder

doi:10.1016/j.ejmech.2022.115020

Cited by 20 publications

(7 citation statements)

References 95 publications

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“…Attractively, the acquired expression of p53 protein in the atypical spindle cells possibly indicated the p53 genetic alteration may trigger and/or contribute to their oncogenesis. In fact, p53 gene mutation has been demonstrared to play pivotal roles in the tumorigenesis of a variety of neoplasms ( 18 , 19 ). A clonality analysis on the two cellular components might be helpful to fully unravel their internal relationship.…”

Section: Discussionmentioning

confidence: 99%

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Case report: The stroma-rich variant of Castleman’s disease of hyaline-vascular type with atypical stromal cell proliferation and malignant potential: An exceptional rare case occurred in mediastinal lymph node

et al. 2023

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The stroma-rich variant of Castleman disease of hyaline-vascular type (SR-HVCD) is characterized by interfollicular proliferation of the fibroblastic, myofibroblastic, and/or histiocytic-derived stromal cells, occurred in a background of Castleman disease of hyaline-vascular type (HVCD). It has been considered as a hyperplastic disorder by far. Herein, we presented a case of a 40-year-old male suffering from an occupation in the right middle mediastinum. Microscopically, the lesion was characterized by atretic lymphoid follicles and overgrowth of the interfollicular spindle-shaped cells. Those spindle cells were histologically bland in some areas, while exhibited notable cellular atypia and focal necrosis in other areas. SMA and CD68 were immunostained with a subset of the spindle cells in both areas, whereas p53 staining was only perceived in areas with markedly cellular atypia. In addition, indolent T-lymphoblastic proliferation (iT-LBP) was present inside the lesion. The patient developed multiple sites metastases 4 months after surgery, and succumbed to the disease at 7 months. Our case demonstrates for the first time that SR-HVCD have a tumorigenesis potential rather than a simple hyperplastic process. Such disorder should be carefully evaluated to avoid underdiagnosis.

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Section: Discussionmentioning

confidence: 99%

“…their oncogenesis. In fact, p53 gene mutation has been demonstrared to play pivotal roles in the tumorigenesis of a variety of neoplasms (18,19). A clonality analysis on the two cellular components might be helpful to fully unravel their internal relationship.…”

Section: Discussionmentioning

confidence: 99%

Case report: The stroma-rich variant of Castleman’s disease of hyaline-vascular type with atypical stromal cell proliferation and malignant potential: An exceptional rare case occurred in mediastinal lymph node

et al. 2023

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“…153 Recent studies have found that TIP60 and MOF have the same ability to acetylate lysine residues on p53, which can promote the transcriptional activation ability of p53 and avoid its ubiquitination. 154,155 Multiple p53 negative regulators, including MDM2 and ArfBP1, are inactivated by alternate reading frame (ARF) targeting, which is common during nucleolar stress. 156 The nucleolus is a large organelle without a nuclear membrane and is primarily responsible for the biogenesis of ribosomes.…”

Section: P53 Activation-related Factorsmentioning

confidence: 99%

“…Both TIP60 and MOF are members of the MYST family and were found earlier to have the function of acetylating histone lysine residues 153 . Recent studies have found that TIP60 and MOF have the same ability to acetylate lysine residues on p53, which can promote the transcriptional activation ability of p53 and avoid its ubiquitination 154,155 …”

Section: Activation and Inactivation Of P53mentioning

confidence: 99%

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Targeting the p53 signaling pathway in cancers: Molecular mechanisms and clinical studies

Shen¹,

Wang²,

Mao³

et al. 2023

MedComm

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Tumor suppressor p53 can transcriptionally activate downstream genes in response to stress, and then regulate the cell cycle, DNA repair, metabolism, angiogenesis, apoptosis, and other biological responses. p53 has seven functional domains and 12 splice isoforms, and different domains and subtypes play different roles. The activation and inactivation of p53 are finely regulated and are associated with phosphorylation/acetylation modification and ubiquitination modification, respectively. Abnormal activation of p53 is closely related to the occurrence and development of cancer. While targeted therapy of the p53 signaling pathway is still in its early stages and only a few drugs or treatments have entered clinical trials, the development of new drugs and ongoing clinical trials are expected to lead to the widespread use of p53 signaling‐targeted therapy in cancer treatment in the future. TRIAP1 is a novel p53 downstream inhibitor of apoptosis. TRIAP1 is the homolog of yeast mitochondrial intermembrane protein MDM35, which can play a tumor‐promoting role by blocking the mitochondria‐dependent apoptosis pathway. This work provides a systematic overview of recent basic research and clinical progress in the p53 signaling pathway and proposes that TRIAP1 is an important therapeutic target downstream of p53 signaling.

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Investigating Therapies Targeting Druggable Targets of Mitochondria: Exploring the Efficacy for the Treatment of Cancer

Kumar Goel,

Rawat,

Murti

et al. 2024

ChemistrySelect

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Cancer is a growing problem that has not yet been fully harnessed. Frequent mutations make this a highly variable and challenging pathology. Interestingly, mitochondria have currently emerged as a new target for cancer therapy. A group of agents with anticancer activity, termed mitocans that encourage apoptosis through mitochondrial disruption is currently important in research. From conventional glycolytic inhibitors to recent radiolabeled compounds, mitochondrial‐targeted therapies have marked their presence in cancer. Several TCA cycle and OXPHOS inhibitors are being established for their possible anticancer properties. There are so many distinctive differences in mitochondrial structure and function between normal and cancer cells that offer the potential for the clinical use of mitochondria as targets for novel and site‐specific anticancer agents. Mitochondrial targeting can be made possible if the bioactive molecule is specifically and selectively delivered to the mitochondria of the correct cell type using cell‐specific ligands and mitochondriotropic molecules.

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p53 as a potential target for treatment of cancer: A perspective on recent advancements in small molecules with structural insights and SAR studies

Cited by 20 publications

References 95 publications

Case report: The stroma-rich variant of Castleman’s disease of hyaline-vascular type with atypical stromal cell proliferation and malignant potential: An exceptional rare case occurred in mediastinal lymph node

Case report: The stroma-rich variant of Castleman’s disease of hyaline-vascular type with atypical stromal cell proliferation and malignant potential: An exceptional rare case occurred in mediastinal lymph node

Targeting the p53 signaling pathway in cancers: Molecular mechanisms and clinical studies

Investigating Therapies Targeting Druggable Targets of Mitochondria: Exploring the Efficacy for the Treatment of Cancer

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