Recent Advances of WEE1 Inhibitors and Statins in Cancers With p53 Mutations

Frontiers in Medicine - Tập 8
Xiangbing Meng1,2, Jason Z. Gao1, Sean Michael T. Gomendoza1, John Wing Li3,1, Shujie Yang1,2
1Department of Pathology, The University of Iowa, Iowa City, IA, United States
2Holden Comprehensive Cancer Center, Carver College of Medicine, University of Iowa, Iowa City, IA, United States
3Department of Human and Evolutionary Biology, University of Southern California, Los Angeles, CA, United States

Tóm tắt

p53 is among the most frequently mutated tumor suppressor genes given its prevalence in >50% of all human cancers. One critical tumor suppression function of p53 is to regulate transcription of downstream genes and maintain genomic stability by inducing the G1/S checkpoint in response to DNA damage. Tumor cells lacking functional p53 are defective in the G1/S checkpoint and become highly dependent on the G2/M checkpoint to maintain genomic stability and are consequently vulnerable to Wee1 inhibitors, which override the cell cycle G2/M checkpoint and induce cell death through mitotic catastrophe. In addition to the lost tumor suppression function, many mutated p53 (Mutp53) proteins acquire gain-of-function (GOF) activities as oncogenes to promote cancer progression, which manifest through aberrant expression of p53. In cancer cells with GOF Mutp53, statins can induce CHIP-mediated degradation of Mutp53 within the mevalonate pathway by blocking the interaction between mutp53 and DNAJA1. Therefore, targeting critical downstream pathways of Mutp53 provides an alternative strategy for treating cancers expressing Mutp53. In this review, we summarize recent advances with Wee1 inhibitors, statins, and mevalonate pathway inhibitors in cancers with p53 mutations.

Từ khóa


Tài liệu tham khảo

Baugh, 2018, Why are there hotspot mutations in the TP53 gene in human cancers?, Cell Death Differ., 25, 154, 10.1038/cdd.2017.180

Chu, 2019, ALOX12 is required for p53-mediated tumour suppression through a distinct ferroptosis pathway, Nat Cell Biol., 21, 579, 10.1038/s41556-019-0305-6

Zhang, 2020, Gain-of-function mutant p53 in cancer progression and therapy, J Mol Cell Biol., 12, 674, 10.1093/jmcb/mjaa040

Zhu, 2020, Mutant p53 in cancer progression and targeted therapies, Front Oncol., 10, 595187, 10.3389/fonc.2020.595187

Schulz-Heddergott, 2018, Gain-of-Function (GOF) mutant p53 as actionable therapeutic target, Cancers (Basel)., 10, 188, 10.3390/cancers10060188

Jiang, 2015, Ferroptosis as a p53-mediated activity during tumour suppression, Nature., 520, 57, 10.1038/nature14344

Li, 2012, Tumor suppression in the absence of p53-mediated cell-cycle arrest, apoptosis, and senescence, Cell., 149, 1269, 10.1016/j.cell.2012.04.026

Kang, 2017, Autophagy and Ferroptosis - What's the Connection?, Curr Pathobiol Rep., 5, 153, 10.1007/s40139-017-0139-5

Parrales, 2018, The interplay between mutant p53 and the mevalonate pathway, Cell Death Differ., 25, 460, 10.1038/s41418-017-0026-y

Omori, 2019, Statins improve survival in patients previously treated with nivolumab for advanced non-small cell lung cancer: An observational study, Mol Clin Oncol., 10, 137, 10.3892/mco.2018.1765

Parrales, 2016, DNAJA1 controls the fate of misfolded mutant p53 through the mevalonate pathway, Nat Cell Biol., 18, 1233, 10.1038/ncb3427

Viswanathan, 2017, Dependency of a therapy-resistant state of cancer cells on a lipid peroxidase pathway, Nature., 547, 453, 10.1038/nature23007

Fradejas, 2013, Mammalian Trit1 is a tRNA([Ser]Sec)-isopentenyl transferase required for full selenoprotein expression, Biochem J., 450, 427, 10.1042/BJ20121713

Shimada, 2016, Global survey of cell death mechanisms reveals metabolic regulation of ferroptosis, Nat Chem Biol., 12, 497, 10.1038/nchembio.2079

Duarte, 2021, The potential use of simvastatin for cancer treatment: A review, Biomed Pharmacother., 141, 111858, 10.1016/j.biopha.2021.111858

Jiang, 2021, Statins: a repurposed drug to fight cancer, J Exp Clin Cancer Res., 40, 241, 10.1186/s13046-021-02041-2

Chen, 2021, Broadening horizons: the role of ferroptosis in cancer, Nat Rev Clin Oncol., 18, 280, 10.1038/s41571-020-00462-0

Murtola, 2021, Statins for prostate cancer: when and how much?, Clin Cancer Res., 10.1158/1078-0432.CCR-21-1891

Sun, 2018, WEE1 kinase inhibition reverses G2/M cell cycle checkpoint activation to sensitize cancer cells to immunotherapy, Oncoimmunology., 7, e1488359, 10.1080/2162402X.2018.1488359

Xing, 2020, A novel BCMA PBD-ADC with ATM/ATR/WEE1 inhibitors or bortezomib induce synergistic lethality in multiple myeloma, Leukemia., 34, 2150, 10.1038/s41375-020-0745-9

Mueller, 2015, WEE1 kinase as a target for cancer therapy, J Clin Oncol., 33, 3485, 10.1200/JCO.2015.62.2290

el-Deiry, 1993, WAF1, a potential mediator of p53 tumor suppression, Cell, 75, 817, 10.1016/0092-8674(93)90500-P

Meng, 2018, AZD1775 Increases sensitivity to olaparib and gemcitabine in cancer cells with p53 mutations, Cancers (Basel), 10, 149, 10.3390/cancers10050149

Do, 2013, Wee1 kinase as a target for cancer therapy, Cell Cycle., 12, 3159, 10.4161/cc.26062

Heijink, 2015, A haploid genetic screen identifies the G1/S regulatory machinery as a determinant of Wee1 inhibitor sensitivity, Proc Natl Acad Sci U S A., 112, 15160, 10.1073/pnas.1505283112

Do, 2015, Phase I study of single-agent AZD1775 (MK-1775), a wee1 kinase inhibitor, in patients with refractory solid tumors, J Clin Oncol., 33, 3409, 10.1200/JCO.2014.60.4009

Leijen, 2016, Phase I study evaluating WEE1 inhibitor AZD1775 as monotherapy and in combination with gemcitabine, cisplatin, or carboplatin in patients with advanced solid tumors, J Clin Oncol., 34, 4371, 10.1200/JCO.2016.67.5991

Topatana, 2020, Advances in synthetic lethality for cancer therapy: cellular mechanism and clinical translation, J Hematol Oncol., 13, 118, 10.1186/s13045-020-00956-5

Tolcher, 2021, Clinical activity of single-agent ZN-c3, an oral WEE1 inhibitor, in a phase 1 dose-escalation trial in patients with advanced solid tumors [abstract], Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21, 81

Magnussen, 2012, High expression of Wee1 is associated with poor disease-free survival in malignant melanoma: potential for targeted therapy, PLoS ONE., 7, e38254, 10.1371/journal.pone.0038254

Patel, 2019, Enhancing direct cytotoxicity and response to immune checkpoint blockade following ionizing radiation with Wee1 kinase inhibition, Oncoimmunology., 8, e1638207, 10.1080/2162402X.2019.1638207

Friedman, 2018, Inhibition of WEE1 kinase and cell cycle checkpoint activation sensitizes head and neck cancers to natural killer cell therapies, J Immunother Cancer., 6, 59, 10.1186/s40425-018-0374-2

Marin-Acevedo, 2021, Immunotherapies targeting stimulatory pathways and beyond, J Hematol Oncol., 14, 78, 10.1186/s13045-021-01085-3

Charap, 2020, Landscape of natural killer cell activity in head and neck squamous cell carcinoma, J Immunother Cancer, 8, e001523, 10.1136/jitc-2020-001523

Ren QW Yu, 2021, Statin associated lower cancer risk and related mortality in patients with heart failure, Eur Heart J., 42, 10.2139/ssrn.3752661

Li, 2020, Ferroptosis: past, present and future, Cell Death Dis., 11, 88, 10.1038/s41419-020-2298-2

Lu, 2021, Simvastatin induces ferroptosis in breast cancer cells by inhibiting GPX4 and sensitizes chemotherapy [abstract], Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX, 81

Kobayashi, 2019, Is antidyslipidemic statin use for cancer prevention a promising drug repositioning approach?, Eur J Cancer Prev., 28, 562, 10.1097/CEJ.0000000000000497

Hopkins, 2019, Mevalonate signaling, COPD and cancer: the statins and beyond, J Investig Med., 67, 711, 10.1136/jim-2018-000829

Cantini, 2020, Statin treatment improves response to anti-PD1 agents in patients with malignant pleural mesothelioma and non-small cell lung cancer, J Clinical Oncology., 38, 3074, 10.1200/JCO.2020.38.15_suppl.3074

Nam, 2021, Statin-mediated inhibition of RAS prenylation activates ER stress to enhance the immunogenicity of KRAS mutant cancer, J Immunother Cancer., 9, e002474, 10.1136/jitc-2021-002474

Bu, 2011, Mechanisms for the anti-inflammatory effects of statins, Curr Opin Lipidol., 22, 165, 10.1097/MOL.0b013e3283453e41

Kagami, 2009, Protein geranylgeranylation regulates the balance between Th17 cells and Foxp3+ regulatory T cells, Int Immunol., 21, 679, 10.1093/intimm/dxp037

Thông tin
Thông tin xuất bản

Frontiers in Medicine

Tập 8

Thông tin tác giả