Article
Oncology
Francis Amirtharaj, Goutham Hassan Venkatesh, Bartosz Wojtas, Hussam Hussein Nawafleh, Ayda Shah Mahmood, Zohra Nausheen Nizami, Munazza Samar Khan, Jerome Thiery, Salem Chouaib
Summary: Pharmacological reactivation of non-functional mutant p53 can be used as a promising strategy to treat tumors carrying this mutation. This study found that APR-246 can increase the functional activity of DNA repair and reduce mutational accumulation. Therefore, APR-246 may be a promising small molecule for controlling genomic instability in p53-mutated tumors.
Article
Environmental Sciences
Yung-Ken Hsu, Hsuan-Ying Chen, Chia-Chieh Wu, Ying-Chih Huang, Cheng-Pu Hsieh, Po-Feng Su, Yi-Fu Huang
Summary: The flavonoid butein demonstrates anti-proliferative effects in human osteosarcoma cells by activating the tumor suppressor p53 and inducing senescence. Additionally, exposure to butein increases reactive oxygen species levels in the cells, leading to enhanced p53 activation and anti-proliferative effects. This suggests that butein is a promising candidate for cancer therapy against osteosarcoma.
ENVIRONMENTAL TOXICOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Sopan Shinde, Dimple Chhabria, Jaypalsing Ingle, Mohit Kumar, Sivapriya Kirubakaran, Sudipta Basu
Summary: In this study, a new small molecule library based on 3-methoxy pyrrole was synthesized and one small molecule that can localize in mitochondria and cause damage was identified through screening in colon cancer cells. This small molecule induced mitochondrial damage by generating reactive oxygen species, inhibiting anti-apoptotic protein Bcl-2 and inducing apoptosis and necrosis, leading to significant inhibition of colon cancer cell proliferation while showing minimal toxicity to normal cells. This finding provides a new direction for mitochondria-targeted colon cancer therapy research.
NEW JOURNAL OF CHEMISTRY
(2022)
Article
Oncology
Shengliang Zhang, Lanlan Zhou, Wafik S. El-Deiry
Summary: This study identified an inducible ROS-ERK2-MDM2 axis as a vulnerability for mutant p53 degradation in cancer cells, which can be targeted by small-molecule compounds for cancer therapy.
MOLECULAR CANCER RESEARCH
(2022)
Article
Oncology
Manabu Endo, Takashi Nishioka, Kento Numazaki, Hiroshi Hasegawa, Tetsu Takahashi, Shunji Sugawara, Hiroyuki Tada
Summary: This study investigated the effect of small molecules that reactivate the tumor suppressor gene p53 on the proliferation of oral squamous cell carcinoma (OSCC) cell lines. The results showed that RITA, one of the small molecules, significantly inhibited the growth of OSCC cells by inducing apoptosis through p53 activation and increased Bax expression.
ANTICANCER RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Jingwen Zhang, Guohua Yu, Yanting Yang, Yingjie Wang, Mengqi Guo, Qikun Yin, Chunhong Yan, Jingwei Tian, Fenghua Fu, Hongbo Wang
Summary: This study revealed a novel mechanism of ubiquitin-dependent p53 degradation via the MDMX-E6AP axis in cervical carcinogenesis. The small-molecule inhibitor of MDMX, XI-011, showed robust anti-proliferation activity in cervical cancer cell lines and promoted apoptosis by stabilizing p53. XI-011 also inhibited tumor growth in mice and enhanced the cytotoxic activity of cisplatin.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Cell Biology
Alexandra E. Herzog, Kristy A. Warner, Zhaocheng Zhang, Emily Bellile, Meera A. Bhagat, Rogerio M. Castilho, Gregory T. Wolf, Peter J. Polverini, Alexander T. Pearson, Jacques E. Nor
Summary: The study highlights the significant role of cancer stem-like cells (CSCs) in the development of head and neck squamous cell carcinoma (HNSCC), and suggests that therapeutic blockade of IL-6R may be a promising strategy to overcome chemoresistance in these patients.
CELL DEATH & DISEASE
(2021)
Article
Chemistry, Multidisciplinary
Hong Yu, Hong-ying Gao, Hua Guo, Gui-zhen Wang, Yi-qing Yang, Qian Hu, Li-jun Liang, Qun Zhao, Da-wei Xie, Yu Rao, Guang-biao Zhou
Summary: RYL-687 inhibits non-small cell lung cancer cells by upregulating p53, which is achieved by inducing reactive oxygen species and upregulating NQO1 to protect p53 from degradation. Targeting NQO1 is a rational strategy to reactivate p53 and RYL-687 has therapeutic potentials in NSCLCs with wild type p53.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Biotechnology & Applied Microbiology
Yuan Feng, Jing Luo, Jintao Cheng, Aimin Xu, Dongbo Qiu, Sixiao He, Dayong Zheng, Changchang Jia, Qi Zhang, Nan Lin
Summary: In this study, a cocktail of three small-molecule compounds (ACY) was used to enhance the proliferation activity of mesenchymal stem cells (MSCs) and reduce cell senescence. ACY also preserved the differentiation potential and upregulated the expression of immunomodulatory factors of MSCs.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Cell Biology
Taichi Nyui, Hironori Yoshino, Tetsuya Nunota, Yoshiaki Sato, Eichi Tsuruga
Summary: cGAS has a role in promoting radioresistance in HNSCC cells, as its knockdown enhances radiosensitivity and increases radiation-induced cell death and senescence.
Review
Biochemistry & Molecular Biology
Yingming Sun, Zhe Wang, Sufang Qiu, Ruoyu Wang
Summary: HNSCC, the 9th most common malignant tumor worldwide, can be divided into HPV-related and HPV-unrelated subtypes based on etiology. HPV-positive HNSCC is more sensitive to treatment with better survival rates, requiring individualized therapy. EGFR amplification and PI3K/AKT/mTOR pathway aberrant activation are common in HPV-positive HNSCC.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Liangping Li, Wenqing Du, Hui Wang, Yufei Zhao, Zetian Huang, Yan Peng, Shulan Zeng, Guohai Zhang
Summary: We report two p53 activators, MX-C2 and MX-C3, with high efficiency and low toxicity, which have the potential for treating oncogene-driven tumors and exhibit broad antitumor activity in NSCLC cells.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Cell Biology
Sophia Ceder, Sofi E. Eriksson, Ying Yu Liang, Emarndeena H. Cheteh, Si Min Zhang, Kenji M. Fujihara, Julie Bianchi, Vladimir J. N. Bykov, Lars Abrahmsen, Nicholas J. Clemons, Paer Nordlund, Sean G. Rudd, Klas G. Wiman
Summary: Asparaginase is a key treatment for acute lymphoblastic leukemia due to the asparagine auxotrophy of ALL blasts, but resistance can occur. TP53 mutations are rare in ALL but associated with poor therapy response, while APR-246 is being tested as a potential treatment for ALL. Combining asparaginase with APR-246 shows synergistic growth suppression in ALL cell lines, suggesting a new treatment strategy.
CELL DEATH & DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Yanli Jin, Seung-Nam Jung, Mi Ae Lim, Chan Oh, Yudan Piao, Hae Jong Kim, QuocKhanh Nguyena, Yea Eun Kang, Jae Won Chang, Ho-Ryun Won, Bon Seok Koo
Summary: The high expression of SHMT2 in head and neck cancer is associated with tumor invasion and metastasis. Silencing SHMT2 inhibits cell proliferation and invasion in HNC, while also affecting the expression of stemness markers and tumor spheroid formation. The study suggests that targeting SHMT2 may play an important role in inhibiting HNC progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Young Yeon Kim, Jee-Hyun Um, Dong Jin Shin, Dae Jin Jeong, Young Bin Hong, Jeanho Yun
Summary: The tumor suppressor p53 regulates mitochondrial dynamics through the PKA-Drp1 pathway, inducing cellular senescence in various cancer and normal cells. It plays an essential role in H-Ras-induced cellular senescence and replicative senescence in normal human cells. Inhibition of PKA activity reduces mitochondrial elongation and cellular senescence in late-passage normal cells, highlighting the importance of the p53-PKA pathway in maintaining the senescence phenotype.
Article
Biology
Jessica M. Molkentine, David P. Molkentine, Kathleen A. Bridges, Tongxin Xie, Liangpeng Yang, Aakash Sheth, Timothy P. Heffernan, David A. Clump, Alma Z. Faust, Robert L. Ferris, Jeffrey N. Myers, Mitchell J. Frederick, Kathryn A. Mason, Raymond E. Meyn, Curtis R. Pickering, Heath D. Skinner
Summary: This study aimed to evaluate the radiosensitizing effects of the PARP inhibitor niraparib and cell cycle checkpoint abrogating drugs in head and neck cancers, finding that HPV status influences radiosensitivity and DNA repair mechanisms.
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
(2021)
Article
Oncology
Carlos E. Cardenas, Beth M. Beadle, Adam S. Garden, Heath D. Skinner, Jinzhong Yang, Dong Joo Rhee, Rachel E. McCarroll, Tucker J. Netherton, Skylar S. Gay, Lifei Zhang, Laurence E. Court
Summary: The study aims to develop a deep learning model to generate high-quality lymph node clinical target volumes for head and neck cancer patients, with VOIs identified using computer vision techniques. The final model achieved high accuracy, with 99% of autosegmented results rated as clinically acceptable.
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2021)
Article
Medicine, Research & Experimental
Paolo A. Ascierto, Lisa H. Butterfield, Katie Campbell, Bruno Daniele, Michael Dougan, Leisha A. Emens, Silvia Formenti, Filip Janku, Samir N. Khleif, Tomas Kirchhoff, Alessandro Morabito, Yana Najjar, Paul Nathan, Kunle Odunsi, Akash Patnaik, Chrystal M. Paulos, Bradley I. Reinfeld, Heath D. Skinner, John Timmerman, Igor Puzanov
Summary: Clinical trials and real-world experience have shown the potential for long-term survival with immunotherapy agents in various malignancies. The success of immune checkpoint blockade has led to the development of other immunotherapies, with over 3000 trials ongoing. The focus of recent discussions has been on evolving topics in cancer immunotherapy and the state of the art across different malignancies.
JOURNAL OF TRANSLATIONAL MEDICINE
(2021)
Article
Oncology
David P. Molkentine, Jessica M. Molkentine, Kathleen A. Bridges, David R. Valdecanas, Annika Dhawan, Reshub Bahri, Andrew J. Hefner, Manish Kumar, Liangpeng Yang, Mohamed Abdelhakiem, Phillip M. Pifer, Vlad Sandulache, Aakash Sheth, Beth M. Beadle, Howard D. Thames, Kathryn A. Mason, Curtis R. Pickering, Raymond E. Meyn, Heath D. Skinner
Summary: Squamous cell carcinoma driven by HPV is more sensitive to radiotherapy, and the p16 protein increases this sensitivity by activating a signaling pathway that affects various proteins involved in transcription and degradation, ultimately reducing homologous recombination and improving the response to radiotherapy.
Article
Pathology
David C. Wilde, Patricia D. Castro, Kaustav Bera, Syeling Lai, Anant Madabhushi, German Corredor, Can Koyuncu, James S. Lewis, Cheng Lu, Mitchell J. Frederick, Allan M. Frederick, Avery E. Haugen, Jose P. Zevallos, Erich M. Sturgis, Justin Shi, Andrew T. Huang, David J. Hernandez, Heath D. Skinner, Jan O. Kemnade, Wendong Yu, Andrew G. Sikora, Vlad C. Sandulache
Summary: This study analyzed the cases of HPV-related OPSCC patients and found that p16, tumor-infiltrating lymphocytes (TILs) and multinucleated tumor cells (MuNI) play a role in predicting patients' prognosis. The results showed a strong relationship between tumor immunity and oncologic outcomes in OPSCC regardless of HPV status, which may provide opportunities for the development of biomarkers and the application of precision oncology approaches.
Article
Multidisciplinary Sciences
Manish Kumar, David Molkentine, Jessica Molkentine, Kathleen Bridges, Tongxin Xie, Liangpeng Yang, Andrew Hefner, Meng Gao, Reshub Bahri, Annika Dhawan, Mitchell J. Frederick, Sahil Seth, Mohamed Abdelhakiem, Beth M. Beadle, Faye Johnson, Jing Wang, Li Shen, Timothy Heffernan, Aakash Sheth, Robert L. Ferris, Jeffrey N. Myers, Curtis R. Pickering, Heath D. Skinner
Summary: The study uncovers that mutations in histone acetyltransferases CREBBP/EP300 can increase homologous recombination, making tumors more sensitive to radiation, and have a synergistic effect with HAT inhibitors. These findings not only provide a resistance mechanism but also offer potential for genomically-driven treatment.
NATURE COMMUNICATIONS
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Wenhua Cao, Mary Gronberg, Adenike Olanrewaju, Thomas Whitaker, Karen Hoffman, Carlos Cardenas, Adam Garden, Heath Skinner, Beth Beadle, Laurence Court
Summary: This study investigates the feasibility of using a knowledge-based planning technique to detect poor quality VMAT plans for patients with head and neck cancer. The results show that the prediction models can accurately assess plan quality, identify suboptimal plans, and assist in the clinical workflow for individual patients.
JOURNAL OF APPLIED CLINICAL MEDICAL PHYSICS
(2022)
Article
Otorhinolaryngology
Steven Borson, Yongli Shuai, Barton F. Branstetter, Marci Lee Nilsen, Marion A. Hughes, Moon Fenton, Mark Kubik, Shaum Sridharan, David A. Clump, Heath D. Skinner, Jonas T. Johnson, Simion Chiosea, James Ohr, Umamaheswar Duvvuri, Seungwon Kim, Katie S. Traylor, Robert Ferris, Dan P. Zandberg
Summary: Definitive local therapy to the primary site in head and neck squamous cell carcinoma (HNSCC) patients, in conjunction with induction and/or immunotherapy, can lead to impressive survival outcomes.
LARYNGOSCOPE INVESTIGATIVE OTOLARYNGOLOGY
(2022)
Article
Cell Biology
S. Carson Callahan, Veena Kochat, Zhiyi Liu, Ayush T. Raman, Margarita Divenko, Jonathan Schulz, Christopher J. Terranova, Archit K. Ghosh, Ming Tang, Faye M. Johnson, Jing Wang, Heath D. Skinner, Curtis R. Pickering, Jeffrey N. Myers, Kunal Rai
Summary: The AT subtype of HNSCC is associated with increased enhancer activity, resistance to enhancer blockade, and increased signaling through certain pathways.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Oncology
Cristina P. Rodriguez, Hyunseok Kang, Jessica L. Geiger, Barbara Burtness, Christine H. Chung, Curtis R. Pickering, Carole Fakhry, Quynh Thu Le, Sue S. Yom, Thomas J. Galloway, Erica Golemis, Alice Li, Jeffrey Shoop Stuart Wong, Ranee Mehra, Heath Skinner, Nabil F. Saba, Elsa R. Flores, Jeffrey N. Myers, James M. Ford, Rachel Karchin, Robert L. Ferris, Charles Kunos, Jean M. Lynn, Shakun Malik
Summary: TP53 mutation is a common genetic event in head and neck squamous cell carcinoma (HNSCC), and efforts are being made to develop novel therapeutic approaches for patients with TP53-mutated tumors through clinical trial planning meetings. The prioritization of concepts for further development was a key outcome of the meeting.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2022)
Meeting Abstract
Oncology
P. Pifer, A. Hefner, J. Molkentine, D. Molkentine, A. Dhawan, L. Yang, C. Pickering, R. Bao, R. L. Ferris, R. B. Patel, J. J. Luke, H. D. Skinner
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2022)
Meeting Abstract
Oncology
A. Dhawan, D. Molkentine, A. Hefner, P. Pifer, R. Bahri, J. Molkentine, C. Pickering, V. C. Sandulache, H. D. Skinner
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2022)
Meeting Abstract
Oncology
David Anthony Clump, Dan Paul Zandberg, Heath Devin Skinner, James Ohr, Moon Jung Fenton, Daniel Paul Normolle, Jonathan Jay Beitler, Julie E. Bauman, Robert L. Ferris
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Meeting Abstract
Oncology
M. K. Abdelhakiem, R. Bao, R. L. Ferris, J. Heymach, C. Pickering, J. J. Luke, H. D. Skinner
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2022)
Meeting Abstract
Oncology
P. Pifer, M. Kumar, L. Yang, T. Xie, M. Frederick, A. Hefner, B. M. Beadle, A. Dhawan, D. Molkentine, J. Molkentine, J. N. Myers, C. Pickering, J. Heymach, H. D. Skinner
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2022)