Article
Oncology
Eytan M. Stein, Daniel J. DeAngelo, Joerg Chromik, Manik Chatterjee, Sebastian Bauer, Chia-Chi Lin, Cristina Suarez, Filip de Vos, Neeltje Steeghs, Philippe A. Cassier, David Tai, Jean-Jacques Kiladjian, Noboru Yamamoto, Rogier Mous, Jordi Esteve, Hironobu Minami, Stephane Ferretti, Nelson Guerreiro, Christophe Meille, Rajkumar Radhakrishnan, Bernard Pereira, Luisa Mariconti, Ensar Halilovic, Claire Fabre, Cecilia Carpio
Summary: This phase I study investigated the recommended dose for expansion of siremadlin, a p53-MDM2 inhibitor, in patients with wild-type TP53 advanced solid or hematologic cancers. The study found recommended doses/regimens for future combination studies. Patients with solid tumors and hematologic malignancies differed in terms of treatment-related adverse events.
CLINICAL CANCER RESEARCH
(2022)
Article
Medicine, General & Internal
Agne Bartnykaite, Aiste Savukaityte, Rasa Ugenskiene, Monika Dauksaite, Erika Korobeinikova, Jurgita Gudaitiene, Elona Juozaityte
Summary: The study found specific SNPs in MDM2 and MDM4 are closely associated with estrogen receptor status, HER2 status, and estrogen/progesterone receptor status in breast cancer, providing potential genetic markers for disease assessment.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Mehregan Babamohamadi, Esmaeil Babaei, Burhan Ahmed Salih, Mahshid Babamohammadi, Hewa Jalal Azeez, Goran Othman
Summary: The p53 protein is a tumor suppressor that regulates various cellular processes and is closely related to cancer development. It can be used as a biomarker for tumor progression and a target for cancer treatment. This review discusses the contribution of wild-type p53 loss of function, its role in ferroptosis and targeted therapy, and challenges and solutions in p53-related drug delivery systems.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Oncology
Junhao Lu, Lihong Chen, Zheng Song, Mousumi Das, Jiandong Chen
Summary: The study showed that lowering core body temperature to 32 degrees Celsius can activate temperature-sensitive p53 mutant in tumors and inhibit tumor growth in a p53-dependent manner. Combining hypothermia with chemotherapy achieved tumor regression and durable remission in a temperature-sensitive p53 lymphoma model, suggesting the potential of using hypothermia to target tumors expressing temperature-sensitive p53 mutations. Pharmacologic inhibition of brain-regulated thermogenesis and induction of whole-body hypothermia at 32 degrees Celsius specifically rescues p53 transcriptional activity and induces tumor regression in the presence of temperature-sensitive p53 mutations.
Review
Oncology
Chiao-En Wu, Chiao-Ping Chen, Wen-Kuan Huang, Yi-Ru Pan, Erhan Aptullahoglu, Chun-Nan Yeh, John Lunec
Summary: This article reviews the role of p53 in GIST and proposes targeting the p53 pathway as a novel treatment strategy for GIST.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Min Deng, Long Zhang, Wenying Zheng, Jiale Chen, Nan Du, Meiqi Li, Weiqing Chen, Yonghong Huang, Ning Zeng, Yuanbin Song, Yongming Chen
Summary: In this study, the increased ac4C mRNA modification and NAT10 expression in gastric cancer (GC) were identified, and NAT10 was found to promote GC development by mediating ac4C acetylation of MDM2 transcript, leading to MDM2 upregulation and p53 downregulation. Furthermore, Helicobacter pylori infection was shown to induce NAT10 expression and contribute to GC development.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Renier C. Heijkants, Amina F. A. S. Teunisse, Danielle de Jong, Kseniya Glinkina, Hailiang Mei, Szymon M. Kielbasa, Karoly Szuhai, Aart G. Jochemsen
Summary: The tumor suppressor protein p53 is frequently repressed in cancer cells by high levels of MDMX and/or MDM2. This study suggests that the oncogenic functions of MDMX can be partially explained by its regulation of FOXO transcription factors, independent of p53.
Article
Oncology
Abhilasha Sinha, Yong Zou, Ayushi S. Patel, Seungyeul Yoo, Feng Jiang, Takashi Sato, Ranran Kong, Hideo Watanabe, Jun Zhu, Pierre P. Massion, Alain C. Borczuk, Charles A. Powell
Summary: This study found that MDM2 amplification and overexpression are associated with invasiveness and poor survival in lung adenocarcinoma. MDM2-targeted therapy effectively suppresses cell proliferation, migration, and invasion in cells with MDM2 amplification/overexpression, but not in cells without MDM2 amplification. Additionally, RNA sequencing identified different signaling pathways affected by MDM2-targeted therapy based on the p53 status of lung adenocarcinoma cells.
Article
Oncology
Immacolata Maietta, Francesca Del Peschio, Preziosa Buonocore, Eleonora Viscusi, Stefano Laudati, Giuseppe Iannaci, Michele Minopoli, Maria Letizia Motti, Valentina De Falco
Summary: This study aimed to verify whether p90RSK can phosphorylate MDM2 at serine 166 and investigate its role in regulating the p53 pathway, especially in thyroid tumors. It has been demonstrated that p90RSK can bind and phosphorylate MDM2 at serine 166, increasing the stability of MDM2 and promoting its degradation of p53. A pharmacological inhibitor of p90RSK, BI-D1870, can decrease MDM2 phosphorylation, restore p53 function, and inhibit cell proliferation while promoting apoptosis.
Article
Multidisciplinary Sciences
Anna Thulin, Carola Andersson, Elisabeth Werner Ronnerman, Shahin De Lara, Chaido Chamalidou, Arnd Schoenfeld, Aniko Kovacs, Henrik Fagman, Fredrik Enlund, Barbro K. Linderholm
Summary: This study aimed to investigate mutations in breast cancer brain metastasis, with TP53 and PIK3CA mutations being the most common, and mutations in other genes also identified. Discordant mutation patterns were found in some matched cases, indicating the need to develop methods for assessing mutational status in brain metastasis.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Ullas Valiya Chembazhi, Wesley S. Tung, Hyojeong Hwang, Yuexi Wang, Aryan Lalwani, Ka Lam Nguyen, Sushant Bangru, Danielle Yee, Kristy Chin, Jing Yang, Auinash Kalsotra, Wenyan Mei
Summary: Intestinal epithelial regeneration is driven by intestinal stem cells. Upon the loss of intestinal stem cells, differentiated intestinal epithelial cells, such as Paneth cells, are capable of acquiring multipotency and contributing to regeneration. Depletion of an RNA-binding protein named PTBP1 in mouse intestinal epithelial cells leads to intestinal stem cell death and epithelial regeneration failure.
NUCLEIC ACIDS RESEARCH
(2023)
Review
Genetics & Heredity
S. K. Janani, S. P. Dhanabal, R. Sureshkumar, Nikitha Upadhyayula Sai Surya, Karthika Chenmala
Summary: This article focuses on the importance of wild-type p53 in breast cancer and the factors that inhibit its function, as well as methods to release p53 by inhibiting the complex and allowing it to act for cancer rehabilitation.
Article
Cell Biology
Maria Manou, Theodoros Loupis, Dimitrios M. Vrachnos, Nikolaos Katsoulas, Stamatios Theocharis, Dimitrios S. Kanakoglou, Efthimia K. Basdra, Christina Piperi, Athanasios G. Papavassiliou
Summary: This study investigated epigenetic regulators and histone-modifying factors in salivary gland tumors (SGTs) and found a network of interacting proteins that affect chromatin structure and histone modifications. These findings provide mechanistic insights into the molecular profile of SGTs.
Review
Genetics & Heredity
Sivakumar Vadivel Gnanasundram, Ondrej Bonczek, Lixiao Wang, Sa Chen, Robin Fahraeus
Summary: Continuous genotoxic stress attacks challenge human cells, leading to DNA damage and potentially cancer development. Cells activate the DNA damage response (DDR) to regulate the cell cycle and repair DNA, with the tumor suppressor p53 playing a key role in this process.
Article
Oncology
Seyed Pairawan, Ming Zhao, Erkan Yuca, Allen Annis, Kurt Evans, David Sutton, Luis Carvajal, Jian-Guo Ren, Solimar Santiago, Vincent Guerlavais, Argun Akcakanat, Coya Tapia, Fei Yang, Priya Subash Chandra Bose, Xiaofeng Zheng, Ecaterina Ileana Dumbrava, Manuel Aivado, Funda Meric-Bernstam
Summary: MDM2/MDMX proteins are often elevated in ER+ breast cancer. ALRN-6924 showed significant activity in WT-TP53 cancer cell lines, particularly in combination with chemotherapeutic agents such as paclitaxel. The combination of ALRN-6924 with chemotherapy demonstrated enhanced antitumor efficacy and increased p21 expression in ER+ breast cancer models.
BREAST CANCER RESEARCH
(2021)