Review
Oncology
Upendra K. Soni, Liam Jenny, Rashmi S. Hegde
Summary: The insulin-like growth factor receptor (IGF-1R) has been extensively studied as a potential target in oncology, but the initial promise has not been fulfilled due to resistance mechanisms and toxicities. Lack of patient stratification based on biomarkers in previous clinical trials has been recognized as a limitation. There is now growing interest in revisiting IGF-1R targeted therapeutics with predictive biomarker-driven patient stratification. The sub-cellular localization of IGF-1R has emerged as a potential biomarker.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2023)
Article
Cell Biology
Yu-Tzu Chan, Ruey-Jen Lin, Ya-Hui Wang, Tsai-Hsien Hung, Yenlin Huang, John Yu, Jyh-Cherng Yu, Alice L. Yu
Summary: This study reveals the crucial role of YAP in breast cancer stem cells. Knockdown of YAP reduces the viability and stemness of BCSCs in vitro and tumor formation in vivo. IGF-1R and IGF-1 regulate the expression and localization of YAP, and YAP overexpression increases the expression of IGF-1. Clinical analysis shows that high levels of YAP and IGF-1 are associated with shorter overall survival in basal-like breast cancer patients. In conclusion, the interplay between YAP and the IGF-1/IGF-1R pathway is clinically relevant for sustaining the properties of BCSCs.
CELL COMMUNICATION AND SIGNALING
(2023)
Review
Biochemistry & Molecular Biology
Panpan Wang, Victor C. Y. Mak, Lydia W. T. Cheung
Summary: The insulin-like growth factor (IGF) axis plays important roles in cancer development and metastasis. The type 1 IGF receptor (IGF-1R) is a key member in the IGF axis and has been recognized for its oncogenic role in multiple cancer lineages. This article reviews the occurrence of IGF-1R aberrations and activation mechanisms in cancers, and discusses the available therapeutic agents for IGF-1R inhibition, including antisense oligonucleotide, tyrosine kinase inhibitors, and monoclonal antibodies. Combination therapy targeting IGF-1R and other oncogenic vulnerabilities has shown promise, and new concepts such as blockage of nuclear translocation of IGF-1R are being explored to improve therapeutic efficacy.
Article
Oncology
Yinqi Zhang, Chengqi Gao, Fei Cao, Ying Wu, Shuanggang Chen, Xue Han, Jingqin Mo, Zhiyu Qiu, Weijun Fan, Penghui Zhou, Lujun Shen
Summary: IGF-1 and IGF-1R show inconsistent gene expression levels in various cancer cell lines, with high expression typically detected in most malignant tumors. High expression of IGF-1 is closely associated with unfavorable overall survival in BLCA, CHOL, and LAML patients, while high expression of IGF-1R is closely linked to poor overall survival in BLCA, LIHC, and LUAD patients.
FRONTIERS IN ONCOLOGY
(2021)
Article
Multidisciplinary Sciences
Juliann Chmielecki, Jhanelle E. Gray, Ying Cheng, Yuichiro Ohe, Fumio Imamura, Byoung Chul Cho, Meng-Chih Lin, Margarita Majem, Riyaz Shah, Yuri Rukazenkov, Alexander Todd, Aleksandra Markovets, J. Carl Barrett, Ryan J. Hartmaier, Suresh S. Ramalingam
Summary: By sequencing circulating tumor DNA in patients from the FLAURA trial, this study identifies MET amplification and EGFR C797S mutation as the most frequent acquired resistance mechanisms to first-line osimertinib.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Andrea E. Wahner Hendrickson, Daniel W. Visscher, Xiaonan Hou, Krista M. Goergen, Hunter J. Atkinson, Thomas G. Beito, Vivian Negron, Wilma L. Lingle, Amy K. Bruzek, Rachel M. Hurley, Jill M. Wagner, Karen S. Flatten, Kevin L. Peterson, Paula A. Schneider, Melissa C. Larson, Matthew J. Maurer, Kimberly R. Kalli, Ann L. Oberg, S. John Weroha, Scott H. Kaufmann
Summary: Studies have shown that CHFR levels vary among ovarian cancers but are unlikely to be an independent biomarker for poor response to taxanes. Additionally, CHFR expression is not significantly associated with overall survival or time to progression in high grade serous ovarian cancer patients treated with platinum/taxane chemotherapy. Furthermore, there is no observed association between CHFR expression and paclitaxel sensitivity in patient-derived ovarian cancer xenografts.
Article
Biochemistry & Molecular Biology
Weronika Baszanowska, Magdalena Misiura, Ilona Oscilowska, Jerzy Palka, Wojciech Miltyk
Summary: The study demonstrates that PEPD can stimulate fibroblast proliferation and migration via activation of the EGFR downstream PI3K/Akt/mTOR signaling pathway. It also enhances the expression of proteins associated with EGFR signaling and promotes collagen biosynthesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Chih-Hung Guo, Shiou-Yue Wang, Chieh-Han Chung, Min -Yi Shih, Wen-Chin Li, Pei-Chung Chen, Shih-Yu Lee, Simon Hsia
Summary: This study evaluated the effects of selenium on triple-negative breast cancer cells and found that selenium can induce apoptosis, inhibit cell cycle, stemness, tumor metastasis, and immune checkpoint molecules. Similar effects were observed in human breast cancer cells.
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Syuan-Ling Lin, Chih-Yang Lin, Wei Lee, Chiao-Fang Teng, Woei-Cherng Shyu, Long-Bin Jeng
Summary: This review focuses on the role of IGF/IGF-1R signaling in cancer initiation and proliferation, maintenance of stem cell characteristics, and enhancement of stem cell-based therapeutics. It summarizes the current progress in preclinical IGF-targeted therapies and the function of IGF/IGF-1R signaling in stem cell self-renewal and regenerative medicine.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(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
Wilhelm Flat, Sarah Borowski, Themistoklis Paraschiakos, Christine Blechner, Sabine Windhorst
Summary: High DIAPH1 levels are correlated with increased survival of ovarian cancer patients. Down-regulation of DIAPH1 expression decreases PTX sensitivity and reduces the concentration of stable microtubules. In addition, DIAPH1 enhances the effect of PTX on microtubule stability in a cell-free system. Thus, DIAPH1 increases the response of Ovca cells to PTX.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Oncology
Han Koo, Sangwon Byun, Jieun Seo, Yuri Jung, Dong Chul Lee, Jung Hee Cho, Young Soo Park, Young Il Yeom, Kyung Chan Park
Summary: IGF-1R is commonly overexpressed in solid tumors, but gene amplification is rare. Research shows that PKM2 regulates IGF-1R protein expression by stabilizing the precursor protein through HSP90 binding. Inhibiting PKM2 reduces IGF-1R levels, inhibits AKT activation, and increases apoptotic cell death, suggesting PKM2 as a potential therapeutic target in cancers with dysregulated IGF signaling.
Article
Biochemistry & Molecular Biology
Garima Kaushik, Parthasarathy Seshacharyulu, Sanchita Rauth, Palanisamy Nallasamy, Satyanarayana Rachagani, Rama Krishna Nimmakayala, Raghupathy Vengoji, Kavita Mallya, Ramakanth Chirravuri-Venkata, Amar B. Singh, Jason M. Foster, Quan P. Ly, Lynette M. Smith, Subodh M. Lele, Mokenge P. Malafa, Maneesh Jain, Moorthy P. Ponnusamy, Surinder K. Batra
Summary: Pancreatic cancer stem cells (PCSC) play a crucial role in metastasis and therapy resistance of pancreatic cancer. The combination treatment of afatinib with gemcitabine shows promising results in targeting PCSCs and reducing tumor growth and metastasis. This novel mechanism involving the EGFR/ERK/FOXA2/SOX9 axis may provide a tailored approach to enhance chemotherapy efficacy in various cancer types.
Article
Oncology
Keunchil Park, Jin-Soo Kim, Joo-Hang Kim, Young-Chul Kim, Hoon-Gu Kim, Eun Kyung Cho, Jong-Youl Jin, Miyoung Kim, Angela Marten, Jin-Hyoung Kang
Summary: The study evaluated the real-world safety and efficacy of afatinib in EGFR mutation-positive NSCLC patients in a Korean expanded access program, showing no unexpected safety signals, manageable adverse events, low treatment discontinuation rate, and encouraging efficacy in a broad patient population.
Article
Oncology
Rui Zong, Xiaoman Chen, Jingjing Feng, Shan Xu
Summary: Depletion of IGF-1R has been shown to increase radiosensitivity in colorectal cancer cells, with NVP-ADW742 enhancing cancer cell response to radiation. Furthermore, depletion or inhibition of IGF-1R affects repair pathways for double-strand breaks and cell cycle progression.
Article
Oncology
Said A. Khelwatty, Sharadah Essapen, Alan M. Seddon, Zhen Fan, Helmout Modjtahedi
BRITISH JOURNAL OF CANCER
(2015)
Article
Immunology
Samer Bazzi, Helmout Modjtahedi, Satvinder Mudan, Charles Akle, Georges M. Bahr
Article
Oncology
Nikolaos Ioanou, Alan M. Sedon, Angus Dalgleish, David Mackintosh, Flavio Solca, Helmout Modjtahedi
INTERNATIONAL JOURNAL OF ONCOLOGY
(2016)
Article
Nutrition & Dietetics
Andrius Jaksevicius, Mark Carew, Calli Mistry, Helmout Modjtahedi, Elizabeth I. Opara
Letter
Oncology
Helmout Modjtahedi, Suzanne Eccles
CLINICAL CANCER RESEARCH
(2014)
Article
Immunology
Mohsen Navari, Mehrak Zare, Masoud Javanmardi, Majid Asadi-Ghalehni, Helmout Modjtahedi, Mohammad Javed Rasaee
IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY
(2014)
Article
Food Science & Technology
Elena Polycarpou, Lisiane B. Meira, Simon Carrington, Elizabeth Tyrrell, Helmout Modjtahedi, Mark A. Carew
MOLECULAR NUTRITION & FOOD RESEARCH
(2013)
Review
Pharmacology & Pharmacy
Helmout Modjtahedi, Byoung Chul Cho, Martin C. Michel, Flavio Solca
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2014)
Article
Multidisciplinary Sciences
Said Abdullah Khelwatty, Sharadah Essapen, Izhar Bagwan, Margaret Green, Alan Michael Seddon, Helmout Modjtahedi
Article
Multidisciplinary Sciences
Aryan Stanley, G. Hossein Ashrafi, Alan M. Seddon, Helmout Modjtahedi
SCIENTIFIC REPORTS
(2017)
Article
Biotechnology & Applied Microbiology
Masoud Javanmardi, Mohammad Javad Rasaee, Helmout Modjtahedi, Majid Asadi-Ghalehni, Mohammad Ghaem Maghami
IRANIAN JOURNAL OF BIOTECHNOLOGY
(2014)
Article
Oncology
Said A. Khelwatty, Soozana Puvanenthiran, Sharadah Essapen, Izhar Bagwan, Alan M. Seddon, Helmout Modjtahedi
Summary: The study revealed that high levels of HER2 expression were found in CRC patients treated with cetuximab, which was associated with shorter progression free survival. The results support the emergence of HER2 as a therapeutic target in mCRC patients.
Review
Oncology
Gustavo A. Arias-Pinilla, Helmout Modjtahedi
Summary: Pancreatic cancer is a highly aggressive type of cancer with poor response to current treatments, leading to its high mortality rate worldwide. Monoclonal antibody technology shows promise in discovering novel therapeutic targets and developing more effective treatment options for pancreatic cancer patients, although no mAbs have been approved for this specific cancer type yet. Further research and development in this field may lead to the approval and widespread use of antibody-based agents for the treatment of pancreatic cancer in the future.
Article
Biochemistry & Molecular Biology
Samer Bazzi, Emale El-Darzi, Tina McDowell, Helmout Modjtahedi, Satvinder Mudan, Marcel Achkar, Charles Akle, Humam Kadara, Georges M. Bahr
Summary: The study analyzed the cytokine and chemokines release patterns of human macrophages exposed to different stimuli, revealing distinct differences in cytokine release patterns between macrophages in different activation states.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)