Review
Oncology
Kainan Wu, Fen Chang, Wenming Li, Tongdong Su, Dapeng Lei
Summary: IGF2BPs are RNA-bound proteins that play a crucial part in various cell functions and act as members of the m6A reader family. They are particularly important in tumor metabolism, specifically in head and neck squamous cell carcinoma.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Neha Khera, Asvika Soodhalaagunta Rajkumar, Khlood Abdulkader M. Alkurdi, Zhiao Liu, Hong Ma, Ahmad Waseem, Muy-Teck Teh
Summary: Through transcriptome datamining, 10 multidrug chemoresistance genes were identified in head and neck squamous cell carcinoma. Among them, NEK2 and INHBA showed significant prognostic values in multiple cancer types. Drug library screens discovered two compounds targeting INHBA and NEK2, which resensitized cisplatin-resistant cells.
Review
Oncology
Huimin Lei, Ading He, Yingying Jiang, Min Ruan, Nannan Han
Summary: Cells experience DNA damage daily and have evolved DNA damage response (DDR) pathways to repair DNA damage. Defects in DDR pathways are closely related to the occurrence, development, and treatment of head and neck squamous cell carcinoma (HNSCC). Therefore, targeting DNA repair pathways may be a promising treatment for HNSCC.
FRONTIERS IN ONCOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Sindhu Nair, James A. Bonner, Markus Bredel
Summary: EGFR is overexpressed in head and neck squamous cell carcinoma and anti-EGFR strategies have shown some clinical benefit but often lead to resistance. Mutations in various domains of the EGFR gene can impact drug binding, radiation response, and overall survival in HNSCC patients. Understanding the EGFR mutational landscape and its effects on treatment resistance can help stratify patients for targeted therapies and maximize therapeutic benefits.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Xin Zhou, Xiaoshen Wang
Summary: This review provides a detailed illustration of the biology, genomic features, and immune landscapes of HPV-associated HNSCC, supporting the synergistic effect of radioimmunotherapy. Current evidence and ongoing clinical trials suggest the potential of radioimmunotherapy in recurrent/metastatic or definitive settings. Future challenges include optimization of radiotherapy and the incorporation of novel therapeutic options.
Review
Medicine, General & Internal
Kamila Romanowska, Agnieszka Sobecka, Agnieszka A. Rawluszko-Wieczorek, Wiktoria M. Suchorska, Wojciech Golusinski
Summary: Head and neck squamous carcinoma (HNSCC) is the sixth most prevalent cancer worldwide, with molecular pathogenesis involving cell cycle disorders, intercellular signaling, proliferation, squamous cell differentiation, and apoptosis. In addition to genetic mutations, epigenetic alterations such as DNA methylation and histone modifications play a key role in promoting cancer formation and progression, making them potential biomarkers and therapeutic targets for HNSCC.
Article
Cell Biology
Nils Ludwig, Saigopalakrishna S. Yerneni, Juliana H. Azambuja, Monika Pietrowska, Piotr Widlak, Cynthia S. Hinck, Alicja Gluszko, Miroslaw J. Szczepanski, Teresa Karmer, Isabella Kallinger, Daniela Schulz, Richard J. Bauer, Gerrit Spanier, Steffen Spoerl, Johannes K. Meier, Tobias Ettl, Beatrice M. Razzo, Torsten E. Reichert, Andrew P. Hinck, Theresa L. Whiteside
Summary: Transforming growth factor beta (TGF beta) is a major component of tumor-derived small extracellular vesicles (TEX) that can promote tumor growth and pro-tumor activities in the tumor microenvironment (TME). TGF beta(+) TEX can stimulate macrophage chemotaxis and reprogram primary human macrophages to promote angiogenesis and tumor progression. Inhibition of TGF beta signaling in TEX can suppress these pro-tumor activities in head and neck squamous cell carcinoma (HNSCC).
JOURNAL OF EXTRACELLULAR VESICLES
(2022)
Article
Cell Biology
Peng Zhou, Caiyun Zhang, Xianmin Song, Dadong Zhang, Minhui Zhu, Hongliang Zheng
Summary: We found that Delta Np63 alpha may be a key factor in the resistance of HNSCC cells to Bortezomib, and CYGB plays a crucial role in this process. Delta Np63 alpha regulates the expression of CYGB, which is involved in clearing excessive ROS induced by Bortezomib, thus affecting apoptosis and drug resistance in HNSCC cells.
CELL DEATH & DISEASE
(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.
Article
Oncology
Xing Wang, Natasha Raman, Ghali Lemtiri-Chlieh, Jinhee Chang, Shreya Jagtap, Dipanwita Dutta Chowdhury, Matthew Ballew, Francesca Anna Carrieri, Triet Nguyen, Katriana Nugent, Travis Peck, Michelle S. Levine, Aaron Chan, Christine Lam, Reem Malek, Tung Hoang, Ryan Phillips, ZhuoAn Cheng, Kekoa Taparra, Nick Connis, Christine L. Hann, Andrew Holland, Phuoc T. Tran, Audrey Lafargue, Hailun Wang
Summary: Extra copies of centrosomes are frequently observed in cancer cells and cancer cells have developed strategies to cluster extra-centrosomes. This study investigated the effects of centrosome approved treatment (CCi) and radiotherapy on lung cancer cells, and found that the combination therapy significantly increased the number of NSCLC cells with multipolar spindles, decreased cell viability and colony formation ability in vitro, and delayed tumor growth in vivo. Furthermore, the combination therapy induced the generation of micronuclei and activated cGAS and cGAS-STING pathway in NSCLC cells. These findings suggest that the combination therapy of CCi, radiotherapy, and immunotherapy could be a promising strategy to treat NSCLC.
MOLECULAR CANCER THERAPEUTICS
(2023)
Article
Biology
Danni Cheng, Ke Qiu, Yufang Rao, Minzi Mao, Li Li, Yan Wang, Yao Song, Junren Chen, Xiaowei Yi, Xiuli Shao, Shao Hui Huang, Yi Zhang, Xuemei Chen, Sisi Wu, Shuaishuai Yu, Jun Liu, Haiyang Wang, Xingchen Peng, Daibo Li, Lin Yang, Li Chen, Zhiye Ying, Yongbo Zheng, Meijun Zheng, Binwu Ying, Xiaoxi Zeng, Wei Zhang, Wei Xu, Geoffrey Liu, Fei Chen, Haopeng Yu, Yu Zhao, Jianjun Ren
Summary: By using multi-omics sequencing, a proliferative exhausted CD8(+) T cells cluster (P-Tex) that is beneficial to the survival outcomes of patients with HPV-positive HNSCC was identified. P-Tex cells aggregate in the antigen-presenting cell niches and activate certain signaling pathways, providing modest but persistent anti-tumor effects.
Article
Biochemistry & Molecular Biology
Cristina Stefania Dumitru, Amalia Raluca Ceausu, Nela Pusa Gaje, Cristian Silviu Suciu, Marius Raica
Summary: This study demonstrates the importance of double immunolabeling in assessing lymphangiogenesis and tumor proliferation in correlation with histopathological grades in HNSCC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Vaishali Chandel, Saurabh Maru, Arun Kumar, Ashok Kumar, Ashok Sharma, Brijesh Rathi, Dhruv Kumar
Summary: Head and Neck tumors exhibit highly altered metabolism, with cancer cells utilizing different pathways for energy production. Monocarboxylate transporters play a crucial role in regulating lactate and maintaining pH balance, essential for cancer cell survival and growth control.
Article
Oncology
Alan L. Ho, Irene Brana, Robert Haddad, Jessica Bauman, Keith Bible, Sjoukje Oosting, Deborah J. Wong, Myung-Ju Ahn, Valentina Boni, Caroline Even, Jerome Fayette, Maria Jose Flor, Kevin Harrington, David S. Hong, Sung-Bae Kim, Lisa Licitra, Ioanna Nixon, Nabil F. Saba, Stephan Hackenberg, Pol Specenier, Francis Worden, Binaifer Balsara, Mollie Leoni, Bridget Martell, Catherine Scholz, Antonio Gualberto
Summary: This study evaluated the efficacy of Tipifarnib in patients with HRAS mutations in R/M HNSCC, showing an objective response rate of 55% in high-VAF HNSCC patients. Tipifarnib demonstrated longer progression-free survival and overall survival compared to previous therapies, with the most frequent treatment-emergent adverse events being anemia and lymphopenia.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Article
Oncology
Zongtai Qi, Yating Liu, Michael Mints, Riley Mullins, Reilly Sample, Travis Law, Thomas Barrett, Angela L. Mazul, Ryan S. Jackson, Stephen Y. Kang, Patrik Pipkorn, Anuraag S. Parikh, Itay Tirosh, Joseph Dougherty, Sidharth V. Puram
Summary: Tumors are composed of diverse cells rather than a uniform ball of cells. Recent studies have shown that deconvolution algorithms can be used to computationally estimate cell-type proportions from gene expression data, although their performance in tumor tissues remains unclear.
Review
Oncology
C. Norman Coleman, Iris Eke, Adeola Y. Makinde, Sunita Chopra, Sandra Demaria, Silvia C. Formenti, Shannon Martello, Michelle Bylicky, James B. Mitchell, Molykutty J. Aryankalayil
CLINICAL CANCER RESEARCH
(2020)
Article
Cell Biology
Sara Sofia Deville, Susanne Luft, Maria Kaufmann, Nils Cordes
CELL DEATH & DISEASE
(2020)
Article
Oncology
Annina Meerz, Sara Sofia Deville, Johannes Mueller, Nils Cordes
Summary: Treatment resistance is a major obstacle for HNSCC patients, and proton beam therapy may offer benefits due to optimized dose distribution. However, molecular data on tumor cell responses to proton irradiation are limited. Despite differences in kinome profiles upon photon and proton irradiation, they were not therapeutically exploitable. Pharmacological inhibition of selected targets showed sensitization independent of radiation type. High-precision proton beam therapy is intensively discussed as a potential approach for better tumor control.
Article
Oncology
Iris Eke, Molykutty J. Aryankalayil, Michelle A. Bylicky, Veit Sandfort, Claire Vanpouille-Box, Saravanan Nandagopal, Edward E. Graves, Amato J. Giaccia, C. Norman Coleman
Summary: The expression of immune-related genes in cancer cells can be altered by radiotherapy, depending on the fractionation regimen used. Long-term changes in gene expression were observed in PC3 and LNCaP prostate cancer cells after irradiation, with implications for immune response. T-cell-mediated cytotoxicity was significantly increased in PC3 cells after a single 10 Gy dose of radiation, and this effect could be further enhanced by treatment with immune checkpoint inhibitors. Understanding and targeting the impact of irradiation on immune-related genes may be a promising strategy for treating primary prostate cancer and recurrent tumors.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2022)
Article
Medicine, Research & Experimental
Molykutty J. Aryankalayil, Shannon Martello, Michelle A. Bylicky, Sunita Chopra, Jared M. May, Aman Shankardass, Laurel MacMillan, Landy Sun, Jaleal Sanjak, Claire Vanpouille-Box, Iris Eke, C. Norman Coleman
Summary: Radiation-induced changes in RNA expression, including mRNAs, miRNAs, and lncRNAs, could serve as predictive markers for normal tissue toxicities and potential targets for developing radiation countermeasures and improving radiotherapy treatment plans.
JOURNAL OF TRANSLATIONAL MEDICINE
(2021)
Article
Medicine, Research & Experimental
Iris Eke, Michelle A. Bylicky, Veit Sandfort, Sunita Chopra, Shannon Martello, Edward E. Graves, C. Norman Coleman, Molykutty J. Aryankalayil
Summary: The study revealed that the upregulation of LINC00261 and LINC00665 long non-coding RNAs in tumors after radiotherapy may have a negative impact on the overall survival of prostate cancer patients. Knockdown of these lncRNAs affected DNA repair protein expression and microRNA levels, leading to reduced survival after reirradiation. Understanding long-term tumor adaptation mechanisms could facilitate the discovery of new molecular targets for improved multimodal radiation oncologic treatments.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2021)
Article
Oncology
Bin Lan, Siyuan Zeng, Shuman Zhang, Xiaofan Ren, Yuming Xing, Isabella Kutschick, Susanne Pfeffer, Benjamin Frey, Nathalie Britzen-Laurent, Robert Gruetzmann, Nils Cordes, Christian Pilarsky
Summary: Pancreatic cancer is the fourth leading cause of cancer-related deaths in Western countries. Radiation therapy has not yielded satisfactory results in treating pancreatic cancer, and understanding radioresistance mechanisms and developing new therapeutic targets have become major challenges. In this study, the researchers used CRISPR-Cas9 screening and 3D cell culture to identify DYRK1A as a sensitive target for radiotherapy in pancreatic cancer. Furthermore, they showed that DYRK1A-targeted inhibitors could enhance the efficacy of radiotherapy. These findings support the use of CRISPR-Cas9 screening to identify novel therapeutic targets and develop strategies to improve radiotherapy efficacy in pancreatic cancer.
Correction
Oncology
Annina Meerz, Sara Sofia Deville, Johannes Mueller, Nils Cordes
Article
Oncology
Stefanie Moritz, Matthias Krause, Jessica Schlatter, Nils Cordes, Anne Vehlow
Summary: Glioblastoma patients face poor prognosis due to aggressive invasion and therapy resistance, with Lamellipodin playing a key role in mediating these processes. The study highlights a novel Lamellipodin-RICTOR-EGFR signaling axis contributing to glioblastoma radiation survival, adding a critical facet to the complex resistance network in glioblastoma.
Article
Cell Biology
Anne Vehlow, Nils Cordes
Summary: This study investigates the crosstalk between β1 integrins and growth factor receptor signaling and its impact on cellular radiation response in fibroblasts. The results show that the cooperation between β1 integrins and growth factor receptors is essential for enhancing radiation-induced cell cycle arrest and improving clonogenic survival.
IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL
(2022)
Article
Multidisciplinary Sciences
Iris Eke, Molykutty J. Aryankalayil, Michelle A. Bylicky, Adeola Y. Makinde, Lance Liotta, Valerie Calvert, Emanuel F. Petricoin, Edward E. Graves, C. Norman Coleman
Summary: This study analyzed the long-term effects of radiation on the efficacy of molecular targeted drugs, finding that irradiation led to changes in gene expression and protein phosphorylation in cells, along with increased activation of several pathways regulating important cell functions. Cells that survived irradiation showed long-term upregulation and increased activity of multiple molecular targets, and exhibited different sensitivity to various molecular targeted drugs.
SCIENTIFIC REPORTS
(2022)
Article
Cell Biology
Leon J. Blankenstein, Nils Cordes, Leoni A. Kunz-Schughart, Anne Vehlow
Summary: In this study, PAK4 was identified as the main regulator of invasion and radio-chemotherapy resistance in glioblastoma cells. By enhancing the number of DNA double-strand breaks and reducing the expression of DNA repair proteins, PAK4 inhibition could improve the radiosensitivity and impair DNA repair in glioblastoma.
Article
Biochemistry & Molecular Biology
Sandra Classen, Elena Rahlf, Johannes Jungwirth, Nina Albers, Luca Philipp Hebestreit, Alexandra Zielinski, Lena Poole, Marco Groth, Philipp Koch, Thomas Liehr, Stefanie Kankel, Nils Cordes, Cordula Petersen, Kai Rothkamm, Helmut Pospiech, Kerstin Borgmann
Summary: By introducing BRCA1 mutations using CRISPR/Cas9, this study found that these mutations increased both sensitivity and resistance to exogenous DNA damage in breast cancer cells. Resistance was associated with improved DNA double-strand break repair and reduction in replication stress.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Irina Korovina, Anne Vehlow, Achim Temme, Nils Cordes
Summary: Integrin alpha 2 is overexpressed in GBM compared to normal brain, and its deletion causes radiochemosensitization and reduces invasion and adhesion in GBM cells post TMZ-irradiation. Knockdown of integrin alpha 2 impairs cell proliferation without affecting DNA damage repair, and it affects ATF1 activity and modulates ERK1 expression regulated by external signals. Integrin alpha 2-deficiency inhibits tumor growth and extends survival in mice with orthotopically growing GBM xenografts.
Article
Oncology
Iris Eke, H. Henry Guo, Billy W. Loo Jr, Arthur W. Sung, Maximilian Diehn, Lucas Vitzthum, Alexander L. Chin, Michael F. Gensheimer
Summary: This article presents a case of a woman with metastatic adenoid cystic carcinoma who developed symptomatic left phrenic nerve injury 2 years after receiving stereotactic ablative radiation therapy. The article discusses the planning considerations by radiation oncologists and medical physicists, as well as the multidisciplinary medical management of the patient.
PRACTICAL RADIATION ONCOLOGY
(2023)