Article
Multidisciplinary Sciences
Anna Gogleva, Dimitris Polychronopoulos, Matthias Pfeifer, Vladimir Poroshin, Michael Ughetto, Matthew J. Martin, Hannah Thorpe, Aurelie Bornot, Paul D. Smith, Ben Sidders, Jonathan R. Dry, Miika Ahdesmaki, Ultan McDermott, Eliseo Papa, Krishna C. Bulusu
Summary: Resistance to EGFR inhibitors is a major challenge in the treatment of non-small cell lung cancer. The authors developed a recommender system that ranks genes based on diverse types of evidence, identifying potential mechanisms of EGFR inhibitor resistance.
NATURE COMMUNICATIONS
(2022)
Review
Oncology
Juan Bautista Blaquier, Sandra Ortiz-Cuaran, Biagio Ricciuti, Laura Mezquita, Andres Felipe Cardona, Gonzalo Recondo
Summary: The landscape of targeted therapies for EGFR-mutant NSCLC is expanding, but resistance to treatment is a challenge. Understanding and using DNA sequencing has led to the development of innovative strategies to overcome or prevent resistance in the clinical setting.
CLINICAL CANCER RESEARCH
(2023)
Article
Multidisciplinary Sciences
Tereza Vaclova, Ursula Grazini, Lewis Ward, Daniel O'Neill, Aleksandra Markovets, Xiangning Huang, Juliann Chmielecki, Ryan Hartmaier, Kenneth S. Thress, Paul D. Smith, J. Carl Barrett, Julian Downward, Elza C. de Bruin
Summary: T790M subclonality is associated with poorer response to osimertinib and shorter progression-free survival, likely due to co-occurring PIK3CA alterations which can be targeted by PI3K pathway inhibitors.
NATURE COMMUNICATIONS
(2021)
Article
Medicine, Research & Experimental
Dan Yan, Justus M. Huelse, Dmitri Kireev, Zikang Tan, Luxiao Chen, Subir Goyal, Xiaodong Wang, Stephen Frye, Madhusmita Behera, Frank Schneider, Suresh S. Ramalingam, Taofeek Owonikoko, H. Shelton Earp, Deborah DeRyckere, Douglas K. Graham
Summary: Acquired resistance is inevitable in non-small cell lung cancers (NSCLCs) treated with osimertinib (OSI). Activation of MERTK is associated with OSI resistance and inhibition of MERTK kinase can resensitize resistant cells to OSI.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Cell Biology
Carolien Eggermont, Philippe Giron, Maxim Noeparast, Hugo Vandenplas, Pedro Aza-Blanc, Gustavo J. Gutierrez, Jacques De Greve
Summary: In this study, a high-throughput siRNA kinome screen was performed to identify targets involved in functional drug tolerance against EGFR TKI in NSCLC. STYK1 was identified as a potential target that, when downregulated, enhances the effects of EGFR inhibition. The study also found that STYK1 selectively interacts with mutant EGFR and that its downregulation counteracts the upregulation of FGF1 induced by EGFR TKI. Co-targeting EGFR and STYK1 could lead to a better overall outcome for NSCLC patients.
CELL DEATH & DISEASE
(2022)
Review
Oncology
Nathan T. T. Bain, Yang Wang, Surein Arulananda
Summary: This mini-review discusses the issue of relapse in EGFR-mutant NSCLC patients after targeted therapy and explores the mechanistic pathways of tumor dormancy, cellular senescence, and epigenetic changes. Various approaches of utilizing combination therapy to enhance the initial depth of response, increase apoptosis, and target senescence-like dormancy are described. Furthermore, potential novel therapies targeting MRD are highlighted in order to improve outcomes for patients with EGFR-mutant NSCLC.
FRONTIERS IN ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Dongliang Bian, Liangdong Sun, Junjie Hu, Liang Duan, Haoran Xia, Xinsheng Zhu, Fenghuan Sun, Lele Zhang, Huansha Yu, Yicheng Xiong, Zhida Huang, Deping Zhao, Nan Song, Jie Yang, Xiao Bao, Wei Wu, Jie Huang, Wenxin He, Yuming Zhu, Gening Jiang, Peng Zhang
Summary: This study aimed to assess the feasibility of neoadjuvant Afatinib treatment for stage III NSCLC patients. The results showed that Afatinib improved the objective response rate (ORR) in NSCLC patients and caused dynamic changes in the tumor microenvironment.
NATURE COMMUNICATIONS
(2023)
Article
Pharmacology & Pharmacy
Xueting Cai, Jing Miao, Rongwei Sun, Sainan Wang, Miguel Angel Molina-Vila, Imane Chaib, Rafael Rosell, Peng Cao
Summary: Osimertinib-resistant EGFR-mutant NSCLC cell lines showed increased heme levels, while plasma heme levels were also elevated in patients treated with osimertinib. The antimalarial drug DHA was found to reverse osimertinib resistance by enhancing ROS levels and impairing heme metabolism. Combination treatment of osimertinib and DHA inhibited tumor growth and downregulated RTKs in a xenograft mouse model.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Chang Jiang, Nathan P. Ward, Nicolas Prieto-Farigua, Yun Pyo Kang, Anish Thalakola, Mingxiang Teng, Gina M. DeNicola
Summary: The redox regulator NRF2 is hyperactivated in a large percentage of non-small cell lung cancer (NSCLC) cases, which is associated with chemotherapy and radiation resistance. In this study, the researchers identified that the loss of mitochondrial superoxide dismutase 2 (SOD2) enhanced the effectiveness of a superoxide-generating drug, beta-Lapachone. They also found that inhibiting mitochondrial electron transport activity sensitized cells to beta-Lapachone. These findings suggest potential therapeutic strategies to increase ROS sensitivity in NSCLC.
Review
Oncology
Dan Yan, H. Shelton Earp, Deborah DeRyckere, Douglas K. Graham
Summary: MERTK and AXL are abnormally expressed in the majority of NSCLCs, providing a survival advantage for cells and correlating with metastasis, drug resistance, and disease progression. Host tumor infiltrating cells' TAM receptors also play crucial roles in the immunosuppressive tumor microenvironment. These factors make MERTK and AXL attractive targets for NSCLC treatment.
Review
Cell Biology
Dylan A. Farnsworth, Yankuan T. Chen, Georgia de Rappard Yuswack, William W. Lockwood
Summary: Mutant EGFR is a molecular driver of non-small cell lung cancer, and tumors with these mutations often rely on sustained oncogene signaling. While inhibiting EGFR with tyrosine kinase inhibitors has shown clinical benefits, resistance remains a challenge. The genetic mechanisms underlying EGFR dependency and factors allowing tumor cells to escape this dependency are still not fully understood.
Article
Biochemistry & Molecular Biology
Byoung Chul Cho, Dong-Wan Kim, Alexander I. Spira, Jorge E. Gomez, Eric B. Haura, Sang-We Kim, Rachel E. Sanborn, Eun Kyung Cho, Ki Hyeong Lee, Anna Minchom, Jong-Seok Lee, Ji-Youn Han, Misako Nagasaka, Joshua K. Sabari, Sai-Hong Ignatius Ou, Patricia Lorenzini, Joshua M. Bauml, Joshua C. Curtin, Amy Roshak, Grace Gao, John Xie, Meena Thayu, Roland E. Knoblauch, Keunchil Park
Summary: This study evaluated the potential of combining amivantamab and lazertinib in patients with EGFR-mutated NSCLC. The results showed that this combination therapy had improved anti-tumor activity in some patients, with a safety profile similar to monotherapy.
Review
Biochemistry & Molecular Biology
Zhenfang Du, Jinghan Sun, Yunkai Zhang, Nigaerayi Hesilaiti, Qi Xia, Heqing Cui, Na Fan, Xiaofang Xu
Summary: Oncogenic mutations in the EGFR kinase domain are well-established driver mutations in NSCLC. Targeted TKIs specifically designed for these mutations have improved treatment outcomes for patients. Structural analysis has influenced TKI development and understanding of structure will further improve patient outcomes. This review summarizes recent progress on targeted therapy strategies for EGFR-mutant NSCLC based on structure and function analysis.
Review
Immunology
Chunyan Shi, Yan Wang, Jianxin Xue, Xiaojuan Zhou
Summary: ICIs are effective in NSCLC patients regardless of PD-L1 expression, and combination with chemotherapy can improve efficacy. Patients with rare mutations show better response to ICIs in terms of progression-free survival.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Pharmacology & Pharmacy
Frank Aboubakar Nana, Sebahat Ocak
Summary: Osimertinib is now a standard first-line treatment for NSCLC with specific EGFR mutations, however, resistance mechanisms are inevitable. This study discusses acquired resistance mechanisms, specifically the BRAF V600 mutation, in EGFR-mutant NSCLC patients treated with Osimertinib in combination with dabrafenib and trametinib.
Article
Oncology
Xiaofan Pu, Chaolei Zhang, Guoping Ding, Hongpeng Gu, Yang Lv, Tao Shen, Tianshu Pang, Liping Cao, Shengnan Jia
Summary: This study demonstrated the potential utility of the sEV-miRNA d-signature in the diagnosis of PDAC via machine learning methods. A novel sEV biomarker, miR-664a-3p, was identified for the diagnosis of PDAC. It can also potentially promote angiogenesis and metastasis, provide insight into PDAC pathogenesis, and reveal novel regulators of this disease.
TRANSLATIONAL ONCOLOGY
(2024)
Article
Oncology
Jiaping Wang, Zhijuan Xu, Yanli Lai, Yanli Zhang, Ping Zhang, Qitian Mu, Shujun Yang, Yongcheng Sun, Lixia Sheng, Guifang Ouyang
Summary: This study demonstrates the significance of PD-1 in EBV-infected lymphoma cells. Silencing PD-1 enhances the tumor targeting effect of EBV-specific killer T cells on B lymphocytes and attenuates the immune escape effect.
TRANSLATIONAL ONCOLOGY
(2024)
Article
Oncology
Qiliang Peng, Jialong Tao, Yingjie Xu, Yi Shen, Yong Wang, Yang Jiao, Yiheng Mao, Yaqun Zhu, Yulong Liu, Ye Tian
Summary: This study investigates the potential role of lipid metabolism-associated genes (LMAGs) in neoadjuvant chemoradiotherapy (nCRT) and immunotherapy for rectal cancer. The results suggest that the SREBF2 gene is a highly predictive factor for nCRT in rectal cancer and is associated with favorable prognosis. SREBF2 is also closely associated with immune cell infiltration and immunotherapy-related genes.
TRANSLATIONAL ONCOLOGY
(2024)
Article
Oncology
Shiquan Li, Nan Zhang, Yongping Yang, Tongjun Liu
Summary: This study investigated the potential molecular mechanism of SPDEF in immune evasion of colorectal cancer (CRC) and found that it suppresses immune evasion by activating CCL28 through the modulation of M2 polarization of macrophages. These findings provide a new research direction and potential therapeutic target for immunotherapy in CRC.
TRANSLATIONAL ONCOLOGY
(2024)
Article
Oncology
Manas Sehgal, Soundharya Ramu, Joel Markus Vaz, Yogheshwer Raja Ganapathy, Srinath Muralidharan, Sankalpa Venkatraghavan, Mohit Kumar Jolly
Summary: This study investigates the relationship between gene expression patterns and phenotypic plasticity and heterogeneity in colorectal cancer (CRC). The results demonstrate the interconnectedness between different Consensus Molecular Subtypes (CMS) of CRC and specific phenotypes such as epithelial and mesenchymal characteristics. Additionally, the study reveals correlations between metabolic pathways and phenotypic scores, as well as between PD-L1 activity and mesenchymal phenotype. Single-cell RNA sequencing analysis further confirms the heterogeneity of different CMS subtypes. These findings have important implications for understanding CRC heterogeneity and developing targeted therapies.
TRANSLATIONAL ONCOLOGY
(2024)
Article
Oncology
Yutong Zou, Siyao Guo, Yan Liao, Weidong Chen, Ziyun Chen, Junkai Chen, Lili Wen, Xianbiao Xie
Summary: This study found that ceramide metabolism is associated with the progression and clinical outcome of osteosarcoma by analyzing data from osteosarcoma patients. The gene ST3GAL1 plays an important role in osteosarcoma, regulating the tumor immune microenvironment and affecting T cell function. It may become a new target for the treatment of osteosarcoma.
TRANSLATIONAL ONCOLOGY
(2024)
Article
Oncology
Chuanhui Chen, Mengzhi Wan, Xiong Peng, Qing Zhang, Yu Liu
Summary: This study examines the function and mechanism of the ceRNA network centered around GPR37 in LUAD. The findings show that high expression of GPR37 in LUAD tissue samples is associated with poor prognosis, and it may regulate the expression of downstream target genes by competitively binding to lncRNA DLEU1 and miR-4458.
TRANSLATIONAL ONCOLOGY
(2024)
Article
Oncology
Junping Li, Hong Hu, Jinping He, Yuling Hu, Manting Liu, Bihui Cao, Dongni Chen, Xiaodie Ye, Jian Zhang, Zhiru Zhang, Wen Long, Hui Lian, Deji Chen, Likun Chen, Lili Yang, Zhenfeng Zhang
Summary: Sequential administration of CDC7 inhibitor XL413 after carboplatin enhances the chemotherapeutic effect of carboplatin on ovarian cancer cells, possibly by inhibiting homologous recombination repair activity and increasing the accumulation of chemotherapy-induced DNA damage.
TRANSLATIONAL ONCOLOGY
(2024)
Article
Oncology
Madison Catalanotto, Joel Markus Vaz, Camille Abshire, Reneau Youngblood, Min Chu, Herbert Levine, Mohit Kumar Jolly, Ana -Maria Dragoi
Summary: The study demonstrates that loss of FLASH in cancer cells leads to a hybrid E/M phenotype with high epithelial scores, suggesting FLASH acts as a repressor of the epithelial phenotype. Additionally, FLASH expression is inversely correlated with the epithelial score and subsets of mesenchymal markers are distinctly up-regulated in FLASH, NPAT, or SLBP-depleted cells.
TRANSLATIONAL ONCOLOGY
(2024)
Article
Oncology
Xiaorui Wang, Na Li, Minying Zheng, Yongjun Yu, Shiwu Zhang
Summary: Adipocytes are derived from pluripotent mesenchymal stem cells and histone modifications play a key role in their differentiation. Recent studies have shown that cancer stem cells can differentiate into adipocytes, reducing the malignancy of cancer cells.
TRANSLATIONAL ONCOLOGY
(2024)
Article
Oncology
Hana Q. Sadida, Alanoud Abdulla, Sara Al Marzooqi, Sheema Hashem, Muzafar A. Macha, Ammira S. Al-Shabeeb Akil, Ajaz A. Bhat
Summary: Cancer heterogeneity and drug resistance are major obstacles to effective cancer treatment, and epigenetic modifications play a pivotal role in these processes. This review explores essential epigenetic modifications, including DNA methylation, histone modifications, and chromatin remodeling, and discusses their complex contributions to cancer biology. However, the interplay of epigenetic and genetic changes in cancer cells presents unique challenges that must be addressed to fully exploit the potential of epigenetic modifications.
TRANSLATIONAL ONCOLOGY
(2024)
Article
Oncology
Pedro De Marchi, Leticia Ferro Leal, Luciane Sussuchi da Silva, Rodrigo de Oliveira Cavagna, Flavio Augusto Ferreira da Silva, Vinicius Duval da Silva, Eduardo C. A. da Silva, Augusto O. Saito, Vladmir C. Cordeiro de Lima, Rui Manuel Reis
Summary: The TIS and IFN-gamma signatures are predictive biomarkers for identifying NSCLC patients who could potentially benefit from immune checkpoint inhibitor therapies.
TRANSLATIONAL ONCOLOGY
(2024)
Article
Oncology
Giovanni Marchi, Anna Rajavuori, Mai T. N. Nguyen, Kaisa Huhtinen, Sinikka Oksa, Sakari Hietanen, Sampsa Hautaniemi, Johanna Hynninen, Jaana Oikkonen
Summary: The study shows that ctDNA can adequately represent high-grade serous ovarian carcinoma (HGSC), and the mutations observed at relapse suggest personalized therapy options.
TRANSLATIONAL ONCOLOGY
(2024)
Article
Oncology
Yuncang Yuan, Jiawei Fan, Dandan Liang, Shijie Wang, Xu Luo, Yongjie Zhu, Nan Liu, Tingxiu Xiang, Xudong Zhao
Summary: This study demonstrates that csGRP78-directed CAR-T cells can selectively kill pancreatic cancer cells, and the combination with chemotherapy enhances cytotoxicity.
TRANSLATIONAL ONCOLOGY
(2024)
Article
Oncology
Niyati Piplani, Tanusri Roy, Neha Saxena, Shamik Sen
Summary: The glycocalyx, a protective barrier surrounding cells, has been found to play a role in cancer cell proliferation, survival, and metastasis. However, its function in maintaining DNA/nuclear integrity during migration through dense matrices has not been explored. This study shows that the bulkiness of the glycocalyx is inversely associated with nuclear stresses, and highlights its mechanical role in shielding migration-associated stresses.
TRANSLATIONAL ONCOLOGY
(2024)