Article
Oncology
Chun-Xia He, You Lv, Meng Guo, Huan Zhou, Wei Qin, Dong Zhao, Hui-Jin Li, Lu Xing, Xin Zhou, Peng-Quan Li, Feng Yu, Jian-Hua He, Hui-Ling Cao
Summary: The crystal structure of Hsp90(N)-NVP-AUY922 was successfully determined, confirming the strong binding capability between NVP-AUY922 and Hsp90(N). NVP-AUY922 exhibited inhibitory activity on NSCLC cell line H1299 by inhibiting cell proliferation, inducing cell cycle arrest, and promoting cell apoptosis. The newly designed NVP-AUY922 derivatives showed enhanced binding force with Hsp90(N), which contributes to the development of new anti-NSCLC drugs.
FRONTIERS IN ONCOLOGY
(2022)
Article
Cell Biology
Li Li, Dongming Wu, Shihua Deng, Jin Li, Feng Zhang, Ye Zou, Ting Zhang, Ying Xu
Summary: In this study, NVP-AUY922 was found to significantly improve radiation-induced lung injury by inhibiting the activation of ferroptosis. Mechanistically, NVP-AUY922 alleviated RILI by blocking chaperone-mediated lysosomal degradation of GPX4, providing a potential strategy for the development of novel protective agents against RILI.
CELL DEATH DISCOVERY
(2022)
Article
Oncology
Melissa Schwab, Gabriele Multhoff
Summary: This study investigated the impact of the Hsp90 inhibitor NVP-AUY922 on tumor cells. The results showed that NVP-AUY922 can enhance radiosensitivity in tumor cells, particularly in LDH-/- cells. Impaired lipid metabolism in LDH-/- cells reduces membrane Hsp70 expression, leading to increased radiosensitivity.
FRONTIERS IN ONCOLOGY
(2022)
Article
Cell Biology
Hong Zhang, Fanghui Ge, Xindong Shui, Yuling Xiang, Xinxin Wang, Chang Liao, Jiandong Wang
Summary: High levels of NIX protein contribute to poor prognosis in PCPG patients, while also enhancing antioxidant capacity and reducing stress-induced apoptosis in PC12 cells. Targeting NIX could be a supplemental therapeutic strategy for PCPG with high NIX levels.
CELL STRESS & CHAPERONES
(2021)
Article
Cell Biology
Kosuke Tsuji, Eiki Kikuchi, Yuta Takashima, Tetsuaki Shoji, Hirofumi Takahashi, Shotaro Ito, Daisuke Morinaga, Masahiro Kashima, Makie Maeda, Hidenori Kitai, Junko Kikuchi, Jun Sakakibara-Konishi, Satoshi Konno
Summary: Inhibition of non-homologous end joining (NHEJ) can enhance the cytotoxicity of paclitaxel (PTX) by impeding the repair of PTX-induced DNA double-strand breaks (DSBs) during the G1 phase after mitotic slippage. This inhibition synergistically increases the cytotoxic effects of antimitotic drugs in non-small cell lung cancer (NSCLC) cells with intrinsic or acquired PTX resistance resulting from mitotic slippage.
Article
Multidisciplinary Sciences
Ayanda M. Magwenyane, Monsurat M. Lawal, Daniel G. Amoako, Anou M. Somboro, Clement Agoni, Rene B. Khan, NdumisoN. Mhlongo, Hezekiel M. Kumalo
Summary: Heat shock protein 90 (Hsp90) is an attractive target for anticancer drug development. This study used multidimensional computational drug design to identify new compounds that can interact with the ATP pocket of Hsp90 and serve as effective anticancer drugs. Through pharmacophore-based virtual screening, molecular docking, screening, and molecular dynamics simulations, 77 compounds were identified, among which 10 showed favorable binding energy over a known inhibitor. Three compounds (ZINC20411962, ZINC13120102, and ZINC15905860) were found to have the most favored interaction with the N-terminus of Hsp90. Molecular dynamics simulations confirmed the stability of these compounds at the ATP-binding site. ZINC20411962 demonstrated the most stable complex formation, with negative entropy and binding free energy values. The identified compounds interacted with catalytic residues crucial for Hsp90 inhibition and exhibited desirable physicochemical and pharmacokinetic properties.
SCIENTIFIC AFRICAN
(2022)
Review
Oncology
Akshat Malik, John C. Hardman, Yadsan Devabalan, Christopher Nutting, Shreerang Bhide, Kevin Harrington, Clare Schilling, Vinidh Paleri
Summary: A systematic review and meta-analysis was conducted to evaluate occult contralateral nodal metastases (OCM) in patients undergoing bilateral neck dissection for surgically treated oropharyngeal squamous cell carcinoma (OPSCC). The study found that OCM were seen in 9.8% of patients, with a higher rate in cN positive necks compared to cN0 necks. This highlights the importance of considering contralateral neck involvement in the surgical treatment of OPSCC.
Article
Oncology
Kevin J. Harrington, Barbara Burtness, Richard Greil, Denis Soulieres, Makoto Tahara, Gilberto de Castro Jr, Amanda Psyrri, Irene Brana, Neus Baste, Prakash Neupane, Ase Bratland, Thorsten Fuereder, Brett G. M. Hughes, Ricard Mesia, Nuttapong Ngamphaiboon, Tamara Rordorf, Wan Zamaniah Wan Ishak, Jianxin Lin, Burak Gumuscu, Ramona F. Swaby, Danny Rischin
Summary: The study presents a post hoc analysis of the long-term efficacy and progression-free survival in recurrent/metastatic head and neck squamous cell carcinoma patients treated with pembrolizumab and pembrolizumab-chemotherapy as next-line therapy. The results demonstrate favorable clinical efficacy and progression-free survival with pembrolizumab and pembrolizumab-chemotherapy in patients with programmed death ligand 1 (PD-L1) combined positive score (CPS) >= 20, CPS >= 1, and total populations. Subsequent treatments after pembrolizumab-based therapy also showed good efficacy.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Charles M. Rudin, Hardev S. Pandha, Matthew Zibelman, Wallace L. Akerley, Kevin J. Harrington, Daphne Day, Andrew G. Hill, Steven J. O'Day, Timothy D. Clay, Gavin M. Wright, Ross R. Jennens, David E. Gerber, Jonathan E. Rosenberg, Christy Ralph, David C. Campbell, Brendan D. Curti, Jaime R. Merchan, Yixin Ren, Emmett Schmidt, Lisa Guttman, Sumati Gupta
Summary: This study evaluated the efficacy and safety of V937 combined with pembrolizumab in patients with advanced solid tumors. The results showed that the combination therapy had a manageable safety profile, but did not achieve greater efficacy than pembrolizumab monotherapy in non-small cell lung cancer and urothelial cancer.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Review
Oncology
Robert I. Haddad, Kevin Harrington, Makoto Tahara, Petr Szturz, Christophe Le Tourneau, Satu Salmio, Marcis Bajars, Nancy Y. Lee
Summary: For the last 20 years, cisplatin-based chemoradiotherapy has been the standard treatment for locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) patients at high risk of recurrence. However, many patients are ineligible for this treatment due to various reasons. The criteria for cisplatin ineligibility, including age and renal impairment, are still debated. The proportion of cisplatin ineligible patients with resected LA SCCHN remains unclear. This review discusses cisplatin ineligibility considerations, limited clinical evidence, and ongoing clinical trials for alternative treatment options.
CANCER TREATMENT REVIEWS
(2023)
Article
Oncology
Susan Lalondrelle, Jen Lee, Rosalind J. Cutts, Isaac Garcia Murillas, Nik Matthews, Nicholas Turner, Kevin Harrington, Katherine Vroobel, Emily Moretti, Shreerang A. Bhide
Summary: Human papilloma virus (HPV) is a major cause of cervical cancer, and there is currently no reliable method to predict early relapse. We have developed a blood test that can accurately detect HPV-DNA fragments in the blood, which can be used to assess treatment response and monitor relapse.
Article
Oncology
P. Martin, Z. Tsourti, J. Ribeiro, L. Castelo-Branco, E. de Azambuja, S. Gennatas, J. Rogado, M. Sekacheva, S. Susnjal, D. Vinal, R. Lee, S. Khallaf, G. Dimopoulou, S. Pradervand, J. Whisenant, T. K. Choueiri, D. Arnold, K. Harrington, K. Punie, J. Oliveira, O. Michielin, U. Dafni, S. Peters, G. Pentheroudakis, E. Romano
Summary: This paragraph summarizes the results of a study analyzing COVID-19 patients, which found that factors such as symptomatic patients, males, older age, ethnicity other than Asian/Caucasian, Eastern Cooperative Oncology Group performance status >2, body mass index <25, hematological malignancy, progressive disease versus no evident disease, and advanced cancer stage significantly affect COVID-19 outcomes.
Article
Oncology
Simon Crabb, Robin Wickens, Sarah Jane-Bibby, Denise Dunkley, Megan Lawrence, Allen Knight, Robert Jones, Alison Birtle, Robert Huddart, Mark Linch, Jonathan Martin, Adam Coleman, Konstantinos Boukas, Hannah Markham, Gareth Griffiths
Summary: This study aims to evaluate the safety and efficacy of PD-L1 directed immunotherapy atezolizumab in UTSCC patients. Preliminary translational data suggests potential therapeutic value. Through this study, we hope to provide a new treatment option for UTSCC patients.
Article
Oncology
Alexandra J. Rose, Mercedes M. Fleming, Jeffrey C. Francis, Jian Ning, Anton Patrikeev, Ritika Chauhan, Kevin J. Harrington, Amanda Swain
Summary: This study established patient-derived xenograft (PDX) lines and tumor organoid models for salivary gland adenoid cystic carcinoma (ACC), and demonstrated the inhibitory effect of dBET6 on ACC cells. Molecular studies revealed a decrease in BRD4 and MYB protein levels and target gene expression with dBET6 treatment. In vivo experiments showed that dBET6 altered the relative composition of ACC cell types and inhibited their progenitor function.
JOURNAL OF PATHOLOGY
(2023)
Review
Oncology
Nikhil Manish Patel, Georgios Geropoulos, Pranav Harshad Patel, Ricky Harminder Bhogal, Kevin Joseph Harrington, Aran Singanayagam, Sacheen Kumar
Summary: Diagnosis of oesophago-gastric cancer is challenging, but non-invasive risk stratification can identify susceptible patients with pre-malignant or benign diseases. Early oesophago-gastric cancer can be treated sooner following diagnostic confirmation through endoscopic biopsy. Mucins, transmembrane glycoproteins implicated in oesophago-gastric cancer, have the potential to be used as biomarkers for malignant transformation. This systematic review examines the role of mucins in the diagnosis of oesophago-gastric cancer.
Meeting Abstract
Oncology
Georgia M. Beasley, Ari M. VanderWalde, Tawnya L. Bowles, Joseph J. Sacco, Jiaxin Niu, Katy K. Tsai, Jason A. Chesney, Bartosz Chmielowski, Adel Samson, Terence Duane Rhodes, Gino K. In, Anna C. Pavlick, Trisha M. Wise-Draper, Miguel F. Sanmamed, Jeannie Hou, Mark R. Middleton, Kevin Harrington, Celeste Lebbe, Judith Michels, Mohammed M. Milhem
ANNALS OF SURGICAL ONCOLOGY
(2023)
Meeting Abstract
Oncology
Yohann Loriot, Nobuaki Matsubara, Se Hoon Park, Robert A. Huddart, Earle F. Burgess, Nadine Houede, Severine Banek, Brigitte Laguerre, Valentina Guadalupi, Ja Hyeon Ku, Spyros Triantos, Sydney Akapame, Kris Deprince, Sutapa Mukhopadhyay, Arlene O. Siefker-Radtke
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Urology & Nephrology
Arlene O. Siefker-Radtke, Andrea Necchi, Se Hoon Park, Jesus Garcia-Donas, Robert A. Huddart, Earle F. Burgess, Mark T. Fleming, Arash Rezazadeh Kalebasty, Begona Mellado, Sergei Varlamov, Monika Joshi, Ignacio Duran, Scott T. Tagawa, Yousef Zakharia, Keqin Qi, Sydney Akapame, Spyros Triantos, Anne O'Hagan, Yohann Loriot
Summary: This study aimed to understand and manage the treatment-emergent adverse events (TEAEs) of Erdafitinib to optimize fibroblast growth factor receptor inhibitor (FGFRi) treatment. The results showed that early identification and proactive management of select TEAEs can improve or resolve most adverse events in patients, allowing for maximum benefit from FGFRi treatment.
EUROPEAN UROLOGY OPEN SCIENCE
(2023)
Article
Dentistry, Oral Surgery & Medicine
Ashwin Algudkar, Kevin Harrington, Cyrus Kerawala, Izhar Bagwan, Derfel Ap Dafydd
Summary: This study summarizes the imaging recommendations and characteristics of head and neck mucosal melanoma (HNMM), and provides revised guidelines to guide the investigation and management of this rare and aggressive cancer.
ORAL AND MAXILLOFACIAL SURGERY-HEIDELBERG
(2023)
Article
Oncology
K. J. Harrington, E. E. W. Cohen, D. Soulieres, J. Dinis, L. Licitra, M. -j. Ahn, A. Soria, J. -p. Machiels, N. Mach, R. Mehra, B. Burtness, R. F. Swaby, J. Lin, J. Ge, N. Lerman, C. Le Tourneau
Summary: Through a study on patients with HNSCC, it was found that pembrolizumab provided longer overall survival and durable responses in all subgroups of recurrence patterns, regardless of previous treatment.
Article
Urology & Nephrology
Christian D. Fankhauser, Abolghassem Jandari, Laurence Collette, Torgrim Tandstad, Di Maria Jiang, Ugo De Giorgi, Christopher Sweeney, Angelika Terbuch, Michal Chovanec, Robert Huddart, Carsten Bokemeyer, Jorg Beyer, Silke Gillessen
Summary: Levels of serum tumor markers play a crucial role in determining chemotherapy intensity for testicular cancer patients. Using test results before removal of the cancer-bearing testicle instead of immediately before chemotherapy may result in inadequate treatment.
EUROPEAN UROLOGY OPEN SCIENCE
(2023)