Article
Biochemistry & Molecular Biology
Xiao-Shun He, Wen-Long Ye, Yu-Juan Zhang, Xiao-Qin Yang, Feng Liu, Jing-Ru Wang, Xiao-Lu Ding, Yun Yang, Ruo-Nan Zhang, Yuan-Yuan Zhao, Hai-Xia Bi, Ling-Chuan Guo, Wen-Juan Gan, Hua Wu
Summary: In this study, we found that BEST4 promotes cell proliferation and metastasis in colorectal cancer. It activates the Akt signaling pathway by binding to the regulatory subunit p85 alpha of PI3K, leading to the expression of critical regulators such as MYC and CCND1. Additionally, high expression of BEST4 is associated with poor prognosis in patients.
Article
Oncology
Daniel J. Becker, Kyung M. Lee, Steve Y. Lee, Kristine E. Lynch, Danil Makarov, Scott E. Sherman, Christy D. Morrissey, Michael J. Kelley, Julie A. Lynch
Summary: This study evaluated the clinical use of KRAS testing and EGFR mAb treatment in colorectal cancer patients in the Veterans Affairs Healthcare System. The results showed underuse of KRAS testing, especially among older patients and those treated at lower-volume CRC centers, as well as high rates of potentially guideline discordant underuse of EGFR mAb in patients with KRAS-WT tumors. Efforts to understand barriers to precision oncology are needed to maximize patient benefit.
JCO PRECISION ONCOLOGY
(2021)
Article
Multidisciplinary Sciences
Motoki Ono, Tsutomu Miyamoto, Ryoichi Asaka, Junko Uchikawa, Hirofumi Ando, Yasuhiro Tanaka, Manaka Shinagawa, Yusuke Yokokawa, Shiho Asaka, Tian-Li Wang, Ie-Ming Shih, Tanri Shiozawa
Summary: This study aimed to create an EAOC mouse model by transplanting uterine pieces from donor mice, in which Arid1a and/or Pten was conditionally knocked out in endometrial cells, onto the ovarian surface or peritoneum of recipient mice. The results showed that induction of only Pten KO evoked atypical endometriosis, while induction of Arid1a; Pten double-KO evoked structures similar to EAOC. This mouse model provides a useful tool for investigating the mechanisms underlying the development of EAOC.
SCIENTIFIC REPORTS
(2023)
Article
Medicine, Research & Experimental
Nobuhiko Sugito, Kazuki Heishima, Yukihiro Akao
Summary: KRAS mutations are frequently detected in many cancers and are major driver genes. Researchers have developed a chemically modified compound called MIR143#12, which exhibits higher anticancer activity and can suppress cell growth in colorectal and pancreatic cancer by affecting the entire KRAS signaling network.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Article
Oncology
Asimina Koulouridi, Michaela Karagianni, Ippokratis Messaritakis, Maria Sfakianaki, Alexandra Voutsina, Maria Trypaki, Maria Bachlitzanaki, Evangelos Koustas, Michalis Karamouzis, Anastasios Ntavatzikos, Anna Koumarianou, Nikolaos Androulakis, Dimitrios Mavroudis, Maria Tzardi, John Souglakos
Summary: The study reveals that KRAS G12D mutation is associated with better overall survival, while KRAS G12C mutation may indicate worse prognosis in terms of progression-free and overall survival. KRAS exon 3 and exon 4 mutations also have different impacts on progression-free and overall survival.
Article
Biochemistry & Molecular Biology
Jiuna Zhang, Xiaoyu Jiang, Jie Yin, Shiying Dou, Xiaoli Xie, Ting Liu, Yijun Wang, Shuling Wang, Xue Zhou, Dongxuan Zhang, Huiqing Jiang
Summary: RNF141 plays an oncogenic role in colorectal cancer by upregulating KRAS activity, which promotes tumor growth, cell proliferation, migration, and apoptosis by interacting with KRAS to induce its activation and enrichment on the plasma membrane.
Article
Biochemistry & Molecular Biology
Ye-Lim Park, Hwang-Phill Kim, Chan-Young Ock, Dong-Wook Min, Jun Kyu Kang, Yoo Joo Lim, Sang-Hyun Song, Sae-Won Han, Tae-You Kim
Summary: The emergence of RAS/RAF mutant clone is the main feature of EGFR inhibitor resistance in KRAS wild-type colon cancer. In this study, researchers successfully isolated cetuximab-resistant (CR) clonality cells from an in vitro system and found that these cells showed a higher EMT signature and increased expression of CXCL1/5. The study also revealed that CXCL1/5 expression in CR cells was regulated by SNAI2/NFKB and transactivated EGFR through CXCR/MMPI/EGF axis via autocrine signaling.
Article
Oncology
Jeeshan Jiffry, Thongthai Thavornwatanayong, Devika Rao, Elisha J. Fogel, Durvanand Saytoo, Rishika Nahata, Hillary Guzik, Imran Chaudhary, Titto Augustine, Sanjay Goel, Radhashree Maitra
Summary: The study revealed that Pelareorep can enhance its propagation and oncolytic effect in colorectal cancer cells by regulating autophagy-related genes and proteins.
CLINICAL CANCER RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Kunyan He, Guang-Xing Wang, Li-Nan Zhao, Xiao-Fang Cui, Xian-Bin Su, Yi Shi, Tian-Pei Xie, Shang-Wei Hou, Ze-Guang Han
Summary: The compound cinobufagin extracted from Traditional Chinese Medicine showed potent inhibitory effects on the proliferation of cancer cells with EGFR amplification, leading to suppression of tumor growth in vivo. This discovery provides a new therapeutic option for treating malignant glioma and other human cancers expressing EGFR.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Oncology
Rona Yaeger, Riccardo Mezzadra, Jenna Sinopoli, Yu Bian, Michelangelo Marasco, Esther Kaplun, Yijun Gao, HuiYong Zhao, Arnaud Da Cruz Paula, Yingjie Zhu, Almudena Chaves Perez, Kalyani Chadalavada, Edison Tse, Sudhir Chowdhry, Sydney Bowker, Qing Chang, Besnik Qeriqi, Britta Weigelt, Gouri J. Nanjangud, Michael F. Berger, Hirak Der-Torossian, Kenna Anderes, Nicholas D. Socci, Jinru Shia, Yonina R. Murciano-Goroff, Bob Li, James G. Christensen, Jorge S. Reis-Filho, David B. Solit, Elisa de Stanchina, Scott W. Lowe, Neal Rosen, Sandra Misale
Summary: Combining KRASG12C and EGFR inhibitors is an effective treatment for colorectal cancer. However, secondary resistance can reduce its efficacy. Our study found that resistance alterations preventing inhibition of ERK signaling are detected at a low frequency, except for KRASG12C amplification, which increases over time. Upon drug withdrawal, resistant cells undergo senescence, but mTOR signaling remains elevated. Targeting the senescence response may be a potential therapeutic vulnerability to overcome acquired resistance.
Article
Oncology
Xiaobing Wu, Zhifa Li, Nanqi Huang, Xiaodan Li, Rong Chen
Summary: This study identified differential expression of miRNAs in CRC patients with different genotypes, particularly highlighting the significance of analyzing the KRAS genotype.
CANCER MANAGEMENT AND RESEARCH
(2022)
Article
Medicine, General & Internal
Costel Stelian Brinzan, Mariana Aschie, Georgeta Camelia Cozaru, Mariana Deacu, Eugen Dumitru, Ionut Burlacu, Anca Mitroi
Summary: In this study, the mutation frequencies of genes in Romanian colorectal cancer patients were analyzed and compared with clinicopathological variables. The results showed correlations between these mutations and distant metastasis at diagnosis, MSI-H, proximal colon location, and well/moderately differentiated tumors. The findings of this study are generally consistent with data from other populations.
Article
Biochemistry & Molecular Biology
Vlad-Adrian Afrasanie, Mihai-Vasile Marinca, Bogdan Gafton, Teodora Alexa-Stratulat, Alexandra Rusu, Eliza-Maria Froicu, Daniel Sur, Cristian Virgil Lungulescu, Larisa Popovici, Andrei-Vlad Lefter, Irina Afrasanie, Anca-Viorica Ivanov, Lucian Miron, Cristina Rusu
Summary: In this study, the frequency, distribution, coexistence, and clinicopathological and molecular correlations of RAS, BRAF, PIK3CA, and TP53 mutations were investigated in 104 patients with metastatic colorectal cancer from Northeastern Romania. TP53 was the most frequently mutated gene (73.1%), followed by KRAS (45.2%) and PIK3CA (6.7%). The study provides novel insights into genetic variations specific to the population from Northeastern Romania and enables the development of genetic profiles in a developing country with limited access to specialized genetic tests.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Leonie Gebauer, Andrea Nist, Marco Mernberger, Thorsten Stiewe, Roland Moll, Kathleen Stabla, Uwe Klinge, Elisabeth Mack, Cornelia Brendel, Andreas Neubauer
Summary: This study found that there was a significant benefit in overall survival for colorectal cancer patients with combined wild-type PIK3CA and mutated-KRAS tumors who used aspirin.
Article
Ecology
Andrew Woolston, Louise J. Barber, Beatrice Griffiths, Oriol Pich, Nuria Lopez-Bigas, Nik Matthews, Sheela Rao, David Watkins, Ian Chau, Naureen Starling, David Cunningham, Marco Gerlinger
Summary: Analysis of exome sequencing data from 42 baseline and progression biopsies from cetuximab-treated colorectal cancers reveals limited adaptive mutagenesis but shows a chemotherapy-induced mutational signature that is the main contributor of specific driver mutations that are enriched at acquired resistance.
NATURE ECOLOGY & EVOLUTION
(2021)
Article
Oncology
David K. Lau, Rebecca Y. Tay, Yvonne H. Yeung, Fiona Chionh, Jennifer Mooi, Carmel Murone, Effie Skrinos, Timothy J. Price, John M. Mariadason, Niall C. Tebbutt
BRITISH JOURNAL OF CANCER
(2018)
Article
Multidisciplinary Sciences
Lars Togel, Rebecca Nightingale, Rui Wu, Anderly C. Chueh, Sheren Al-Obaidi, Ian Luk, Mercedes Davalos-Salas, Fiona Chionh, Carmel Murone, Daniel D. Buchanan, Zac Chatterton, Oliver M. Sieber, Diego Arango, Niall C. Tebbutt, David Williams, Amardeep S. Dhillon, John M. Mariadason
SCIENTIFIC REPORTS
(2018)
Article
Oncology
Moritz F. Eissmann, Christine Dijkstra, Merridee A. Wouters, David Baloyan, Dmitri Mouradov, Paul M. Nguyen, Mercedes Davalos-Salas, Tracy L. Putoczki, Oliver M. Sieber, John M. Mariadason, Matthias Ernst, Frederick Masson
CANCER IMMUNOLOGY RESEARCH
(2018)
Article
Oncology
J. K. Mooi, P. Wirapati, R. Asher, C. K. Lee, P. Savas, T. J. Price, A. Townsend, J. Hardingham, D. Buchanan, D. Williams, S. Tejpar, J. M. Mariadason, N. C. Tebbutt
ANNALS OF ONCOLOGY
(2018)
Review
Biochemistry & Molecular Biology
Ian Y. Luk, Camilla M. Reehorst, John M. Mariadason
Article
Cell Biology
Erinna F. Lee, Tiffany J. Harris, Sharon Tran, Marco Evangelista, Surein Arulananda, Thomas John, Celeste Ramnac, Chloe Hobbs, Haoran Zhu, Gency Gunasingh, David Segal, Andreas Behren, Jonathan Cebon, Alexander Dobrovic, John M. Mariadason, Andreas Strasser, Leona Rohrbeck, Nikolas K. Haass, Marco J. Herold, W. Douglas Fairlie
CELL DEATH & DISEASE
(2019)
Article
Pathology
David S. Williams, Dmitri Mouradov, Clare Browne, Michelle Palmieri, Meg J. Elliott, Rebecca Nightingale, Catherine G. Fang, Rita Li, John M. Mariadason, Ian Faragher, Ian T. Jones, Leonid Churilov, Niall C. Tebbutt, Peter Gibbs, Oliver M. Sieber
Article
Multidisciplinary Sciences
Mercedes Davalos-Salas, Magdalene K. Montgomery, Camilla M. Reehorst, Rebecca Nightingale, Irvin Ng, Holly Anderton, Sheren Al-Obaidi, Analia Lesmana, Cameron M. Scott, Paul Ioannidis, Hina Kalra, Shivakumar Keerthikumar, Lars Togel, Angela Rigopoulos, Sylvia J. Gong, David S. Williams, Prusoth Yoganantharaja, Kim Bell-Anderson, Suresh Mathivanan, Yann Gibert, Scott Hiebert, Andrew M. Scott, Matthew J. Watt, John M. Mariadason
NATURE COMMUNICATIONS
(2019)
Article
Biochemistry & Molecular Biology
Katie L. Owen, Linden J. Gearing, Damien J. Zanker, Natasha K. Brockwell, Weng Hua Khoo, Daniel L. Roden, Marek Cmero, Stefano Mangiola, Matthew K. Hong, Alex J. Spurling, Michelle McDonald, Chia-Ling Chan, Anupama Pasam, Ruth J. Lyons, Hendrika M. Duivenvoorden, Andrew Ryan, Lisa M. Butler, John M. Mariadason, Tri Giang Phan, Vanessa M. Hayes, Shahneen Sandhu, Alexander Swarbrick, Niall M. Corcoran, Paul J. Hertzog, Peter Croucher, Chris Hovens, Belinda S. Parker
Review
Pharmacology & Pharmacy
Mercedes Davalos-Salas, John M. Mariadason, Matthew J. Watt, Magdalene K. Montgomery
BIOCHEMICAL PHARMACOLOGY
(2020)
Article
Oncology
Jennifer Mooi, Fiona Chionh, Peter Savas, Jessica Da Gama Duarte, Geoffrey Chong, Stephen Brown, Rachel Wong, Timothy J. Price, Alysson Wann, Effie Skrinos, John M. Mariadason, Niall C. Tebbutt
Summary: The study assessed the efficacy and safety of the dual antiangiogenesis agents, bevacizumab plus trebananib, in first-line treatment of metastatic colorectal cancer without chemotherapy. The combination therapy showed durable responses with manageable toxicity profile. The exploratory biomarker results suggested that the combination may enhance the antitumor immune response in immunotolerant colorectal cancer.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
David K. Lau, Ian Y. Luk, Laura J. Jenkins, Andrew Martin, David S. Williams, Kael L. Schoffer, Fiona Chionh, Michael Buchert, Katrin Sjoquist, Alex Boussioutas, Sarah A. Hayes, Matthias Ernst, Andrew J. Weickhardt, Nick Pavlakis, Niall C. Tebbutt, John M. Mariadason
Summary: Amplification or overexpression of the FGFR family is a common occurrence in gastric cancer, with the multikinase inhibitor Regorafenib showing sensitivity in FGFR-driven gastric cancer cell lines. However, the limited clinical response to Regorafenib in the INTEGRATE trial cohort suggests a potential reactivation of MAPK/ERK signaling, which can be overcome by combinatorial inhibition of FGFR and MEK for more effective treatment of FGFR-driven gastric cancers.
MOLECULAR CANCER THERAPEUTICS
(2021)
Article
Cell Biology
Surein Arulananda, Megan O'Brien, Marco Evangelista, Tiffany J. Harris, Nikita S. Steinohrt, Laura J. Jenkins, Marzena Walkiewicz, Robert J. J. O'Donoghue, Ashleigh R. Poh, Bibhusal Thapa, David S. Williams, Trishe Leong, John M. Mariadason, Xia Li, Jonathan Cebon, Erinna F. Lee, Thomas John, W. Douglas Fairlie
CELL DEATH DISCOVERY
(2020)
Article
Multidisciplinary Sciences
David K. Lau, Dmitri Mouradov, Wiphawan Wasenang, Ian Y. Luk, Cameron M. Scott, David S. Williams, Yvonne H. Yeung, Temduang Limpaiboon, George F. Iatropoulos, Laura J. Jenkins, Camilla M. Reehorst, Fiona Chionh, Mehrdad Nikfarjam, Daniel Croagh, Amardeep S. Dhillon, Andrew J. Weickhardt, Toshihide Muramatsu, Yoshimasa Saito, Niall C. Tebbutt, Oliver M. Sieber, John M. Mariadason
Article
Oncology
Higinio Dopeso, Paulo Rodrigues, Josipa Bilic, Sarah Bazzocco, Fernando Carton-Garcia, Irati Macaya, Priscila Guimaraes de Marcondes, Estefania Anguita, Marc Masanas, Lizbeth M. Jimenez-Flores, Augueda Martinez-Barriocanal, Rocio Nieto, Miguel F. Segura, Simo Schwartz, John M. Mariadason, Diego Arango
BRITISH JOURNAL OF CANCER
(2018)