Article
Oncology
John R. P. Knight, Constantinos Alexandrou, George L. Skalka, Nikola Vlahov, Kathryn Pennel, Leah Officer, Ana Teodosio, Georgios Kanellos, David M. Gay, Sebastian May-Wilson, Ewan M. Smith, Arafath K. Najumudeen, Kathryn Gilroy, Rachel A. Ridgway, Dustin J. Flanagan, Rachael C. L. Smith, Laura McDonald, Craig MacKay, Anne Cheasty, Kerri McArthur, Emma Stanway, Joshua D. Leach, Rene Jackstadt, Joseph A. Waldron, Andrew D. Campbell, Georgios Vlachogiannis, Nicola Valeri, Kevin M. Haigis, Nahum Sonenberg, Christopher G. Proud, Neil P. Jones, Martin E. Swarbrick, Heather J. McKinnon, William J. Faller, John Le Quesne, Joanne Edwards, Anne E. Willis, Martin Bushell, Owen J. Sansom
Summary: KRAS-mutant colorectal cancers exhibit resistance to therapeutics, but targeting the mTORC1 and MNK pathways can sensitize them to rapalogs. This approach has shown effectiveness in mouse models and human organoids, offering a potential strategy for patients with elevated c-MYC expression.
Article
Oncology
Jin K. Kim, Michael R. Marco, Seo-Hyun Choi, Xuan Qu, Chin-Tung Chen, Moshe Elkabets, Lauren Fairchild, Oliver Chow, Francisco M. Barriga, Lukas E. Dow, Kevin O'Rourke, Bryan Szeglin, Dmitry Yarilin, Sho Fujisawa, Katia Manova-Todorova, Philip B. Paty, Jinru Shia, Christina Leslie, J. Joshua Smith, Scott Lowe, Raphael Pelossof, Francisco Sanchez-Vega, Julio Garcia-Aguilar
Summary: Somatic mutations in the KRAS oncogene are associated with differences in gene expression related to the tumor microenvironment in locally advanced rectal cancer. Studies in in vitro and in vivo models show that KRAS mutations modulate the activity of surrounding fibroblasts in the tumor microenvironment.
MOLECULAR ONCOLOGY
(2021)
Article
Oncology
Yanfei Liu, Shifeng Tian, Ben Yi, Zhiqiang Feng, Tianhao Chu, Jun Liu, Chunze Zhang, Shiwu Zhang, Yijia Wang
Summary: This study found that platycodin-D can increase the sensitivity of KRAS-mutant colorectal cancer cells to cetuximab by inhibiting the PI3K/Akt signaling pathway, thereby inhibiting tumor cell growth and migration.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Emmanuel Griessinger, Diego Pereira-Martins, Marielle Nebout, Claudie Bosc, Estelle Saland, Emiline Boet, Ambrine Sahal, Johanna Chiche, Delphine Debayle, Lucile Fleuriot, Maurien Pruis, Veronique De Mas, Francois Vergez, Christian Recher, Gerwin Huls, Jean-Emmanuel Sarry, Jan Jacob Schuringa, Jean-Francois Peyron
Summary: Dependency on mitochondrial oxidative phosphorylation (OxPhos) is a potential weakness for leukemic stem cells (LSC) that can be exploited for therapeutic purposes. Fatty acid oxidation (FAO) is a crucial OxPhos-fueling catabolic pathway for some acute myeloid leukemia (AML) cells, particularly chemotherapy-resistant AML cells. Cold sensitivity at 4℃ can selectively kill AML LSCs with active FAO supported OxPhos while sparing normal hematopoietic stem cells.
Article
Gastroenterology & Hepatology
Leiling Pan, Medhanie A. Mulaw, Johann Gout, Min Guo, Hina Zarrin, Peggy Schwarz, Bernd Baumann, Thomas Seufferlein, Martin Wagner, Franz Oswald
Summary: This study found that downregulation of RBPJ in PDAC patients promotes KRAS-mediated transformation of pancreatic acinar cells and development of fibrosis. This finding provides important clues for the development mechanism of PDAC and offers a theoretical basis for finding new treatment strategies.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Oncology
Cloud P. Paweletz, Grace A. Heavey, Yanan Kuang, Emily Durlacher, Thian Kheoh, Richard C. Chao, Alexander I. Spira, Konstantinos Leventakos, Melissa L. Johnson, Sai-Hong Ignatius Ou, Gregory J. Riely, Kenna Anderes, Wenjing Yang, James G. Christensen, Pasi A. Janne
Summary: This study reports on early ctDNA changes of KRAS G12C in lung cancer patients and suggests that ctDNA changes can be used as a potential measure for early prediction of clinical response.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Ruolan You, Bin Wang, Ping Chen, Xiaoming Zheng, Diyu Hou, Xiaoting Wang, Beiying Zhang, Ling Chen, Dongliang Li, Xinjian Lin, Huifang Huang
Summary: This study reveals that metformin can enhance the chemosensitivity of AML cells by inhibiting the mitochondrial transfer from stromal cells. This finding suggests a potential application of metformin in treating AML and provides a novel mechanism for its effect.
Article
Biochemistry & Molecular Biology
Shin Hamada, Ryotaro Matsumoto, Yu Tanaka, Keiko Taguchi, Masayuki Yamamoto, Atsushi Masamune
Summary: Research has shown that Nrf2 activation and glutaminase inhibition may have potential therapeutic effects on K-ras mutant pancreatic cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Marine Lemesle, Marine Geoffroy, Fabien Alpy, Catherine-Laure Tomasetto, Sandra Kuntz, Isabelle Grillier-Vuissoz
Summary: This study investigated the role of CLDN1 in triple-negative breast cancer (TNBC) and found that CLDN1 can increase the sensitivity of TNBC cells to chemotherapy drugs. The findings support the use of CLDN1 as a predictive marker for chemotherapy response in TNBC.
Article
Oncology
Koichi Tomoshige, William D. Stuart, Iris M. Fink-Baldauf, Masaoki Ito, Tomoshi Tsuchiya, Takeshi Nagayasu, Tomoki Yamatsuji, Morihito Okada, Takuya Fukazawa, Minzhe Guo, Yutaka Maeda
Summary: The transcription factor FOXA2 has different effects on lung tumorigenesis depending on the oncogenes present. It inhibits tumor development driven by EGFRL858R but promotes tumor growth driven by KRASG12D. Additionally, FOXA2 induces the expression of MUC5AC, leading to the development of invasive mucinous adenocarcinoma (IMA), a subtype of lung cancer.
Article
Biochemistry & Molecular Biology
Hyeon Jin Kim, Chang Woo Han, Mi Suk Jeong, Se Bok Jang
Summary: KRAS mutations are found in 25% of human cancers and play a role in diverse cellular processes. In this study, the peptide GJ101 was shown to bind directly to the KRAS mutant (G12V) and exhibited tumor-suppressive activity. The complex structure of KRAS and GJ101 was determined by X-ray crystallography, confirming the interaction between residue Q61 and GJ101. These findings suggest that GJ101 could serve as a potential inhibitor for KRAS G12V.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Review
Oncology
Yuta Adachi, Ryo Kimura, Kentaro Hirade, Hiromichi Ebi
Summary: Mutant KRAS-driven tumor cells can become independent of mutant KRAS by activating alternative pathways, leading to a mesenchymal phenotype and potential metastasis. YAP and/or RSK-mTOR pathway activation, along with mutations in LKB1, KEAP1, and/or NRF2, are linked to mutant KRAS autonomy. Understanding KRAS dependency is crucial for selecting patients for mutant-specific inhibitors, while investigating mechanisms of KRAS autonomy is important for developing optimal treatment strategies for KRAS-independent tumors.
Article
Oncology
Mingyue Xia, Shuyan Wang, Yannan Qi, Kaili Long, Enjie Li, Lingfeng He, Feiyan Pan, Zhigang Guo, Zhigang Hu
Summary: Inhibition of O-GlcNAc transferase (OGT) enhances the chemotherapeutic response in prostate cancer (PC) cells. MicroRNA-140 (miR-140) directly inhibits OGT expression and increases the drug sensitivity of PC cells to docetaxel.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Linda J. van Weele, Sabra Djomehri, Shang Cai, Jane Antony, Shaheen S. Sikandar, Dalong Qian, William H. D. Ho, Robert B. West, Ferenc A. Scheeren, Michael F. Clarke
Summary: This study reports a mouse model of breast cancer that develops tumors in the absence of certain genes. The study found that tumors initially regress and enter remission upon inactivation of a specific oncogene, but most tumors later return. The study also identified epithelial-mesenchymal transition and active signaling pathways in tumors that adapt to oncogenic gene inhibition.
MOLECULAR ONCOLOGY
(2022)
Article
Pharmacology & Pharmacy
Yu Ren, Xue Wang, Shuaishuai Huang, Yangkai Xu, Guobin Weng, Rui Yu
Summary: In this study, we found that alternol sensitized renal carcinoma cells to TRAIL-induced apoptosis by inhibiting antiapoptotic proteins, upregulating DR5 levels, ROS generation, and the CHOP pathway, thus enhancing TRAIL-mediated apoptosis.
FRONTIERS IN PHARMACOLOGY
(2021)