Review
Biochemistry & Molecular Biology
Belen Toledo, Manuel Picon-Ruiz, Juan Antonio Marchal, Macarena Peran
Summary: Tumours are complex systems consisting of dynamic interactions between tumour cells, non-tumour cells, and extracellular components that make up the tumour microenvironment (TME). Cancer-associated fibroblasts play a crucial role in extracellular matrix construction, tumour metabolism, immunology, adaptive chemoresistance, and tumour cell motility. The interaction between CAFs and tumour cells has shifted the focus from considering stromal cells as mere physical support to recognizing their importance in the tumour process.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Mi Joung Kim, Daun Jung, Joo Youn Park, Seung Min Lee, Hee Jung An
Summary: This study identified that CAFs in ovarian serous carcinomas support migration and metastasis of ovarian cancer cells through the overexpression of GLIS1. Knockdown of GLIS1 in CAFs significantly inhibited the migration and invasion abilities of OC cells, indicating GLIS1 in CAFs may be a potential therapeutic target to inhibit OC metastasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Xueke Shi, Jingjing Luo, Kelsey J. Weigel, Spencer C. Hall, Danfeng Du, Fanglong Wu, Michael C. Rudolph, Hongmei Zhou, Christian D. Young, Xiao-Jing Wang
Summary: The study demonstrates that TGF beta-enriched CAFs play a critical role in promoting SCC lung metastasis by facilitating tumor cell seeding and growth in the lung. Experimental results show that CAFs enhance tumor volume, inhibit apoptosis, and stimulate cell proliferation and angiogenesis in the lung. The findings suggest that CAFs could serve as a prognostic marker and therapeutic target for SCC lung metastasis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Oncology
Chang-Ik Yoon, Sung-Gwe Ahn, Yoon-Jin Cha, Dooreh Kim, Soong-June Bae, Ji-Hyung Lee, Akira Ooshima, Kyung-Min Yang, Seok-Hee Park, Seong-Jin Kim, Joon Jeong
Summary: The study found that the expression of BAG2 in cancer-associated fibroblasts (CAFs) and tumor cells is closely associated with distant metastasis-free survival in breast cancer patients, and evaluating this expression can help determine the risk of metastasis.
Article
Chemistry, Multidisciplinary
Xiaoli Yi, Yue Yan, Lian Li, Qiuyi Li, Yucheng Xiang, Yuan Huang
Summary: The study presents a sequential combination strategy targeting CAFs depletion and mitochondria disruption to combat metastatic tumors. This dual approach significantly inhibits primary tumor growth and completely eradicates distant metastasis by reducing tumor stroma, increasing intratumoral oxygen perfusion, disrupting cancer cells' aerobic respiration, and downregulating hypoxia-induced PMN-fostering factors.
ADVANCED FUNCTIONAL MATERIALS
(2021)
Article
Endocrinology & Metabolism
Vincenzo Brescia, Antonietta Fontana, Roberto Lovero, Carmela Capobianco, Stella Vita Marsico, Tiziana De Chirico, Carla Pinto, Lucia Varraso, Angela Pia Cazzolla, Francesca Di Serio
Summary: This study establishes the upper reference limit for iFGF23 using an automated immunochemiluminescent assay. This information is important for the diagnosis and monitoring of various forms of rickets in pediatric patients.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Immunology
Xiangxiang Liu, Jian Qin, Junjie Nie, Rui Gao, Shangshang Hu, Huiling Sun, Shukui Wang, Yuqin Pan
Summary: By analyzing RNA sequencing data of colorectal cancer (CRC) patients, this study identified four characteristic genes and determined that the ANGPTL2+CAFs and SPP1+macrophages subtypes are accelerators of CRC metastasis, providing potential therapeutic targets for metastatic CRC.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Xu Zhou, Ruth A. Franklin, Miri Adler, Trevor S. Carter, Emily Condiff, Taylor S. Adams, Scott D. Pope, Naomi H. Philip, Matthew L. Meizlish, Naftali Kaminski, Ruslan Medzhitov
Summary: This article reports on the mechanisms controlling the population numbers of different cell types in animal tissues. The study shows that fibroblasts are limited in proliferation due to space availability, while macrophages are constrained by growth factor availability. The transcriptional coactivator YAP1 in fibroblasts directly regulates the expression of the macrophage-specific growth factor Csf1. The findings suggest that tissue environment sensing is a general strategy for controlling tissue composition.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Gao Liu, Jian Sun, Zhang-Fu Yang, Cheng Zhou, Pei-Yun Zhou, Ruo-Yu Guan, Bao-Ye Sun, Zhu-Tao Wang, Jian Zhou, Jia Fan, Shuang-Jian Qiu, Yong Yi
Summary: CAFs-derived cytokines can enhance hepatocellular carcinoma progression and metastasis by activating the circRNA-miRNA-mRNA axis in tumor cells, with CXCL11 playing a key role in this process.
CELL DEATH & DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Mohamed Amgad, James M. Hodge, Maha A. T. Elsebaie, Clara Bodelon, Samantha Puvanesarajah, David A. Gutman, Kalliopi P. Siziopikou, Jeffery A. Goldstein, Mia M. Gaudet, Lauren R. Teras, Lee A. D. Cooper
Summary: HiPS is a robustly validated biomarker for evaluating the survival risk of breast tumor microenvironment morphology. It outperforms pathologists in predicting survival outcomes, particularly in terms of stromal and immune features.
Letter
Oncology
Xingyi Pan, Jiaojiao Zhou, Qian Xiao, Kenji Fujiwara, Mengwen Zhang, Guanglan Mo, Wei Gong, Lei Zheng
Summary: The study revealed that tumor cells from pancreatic ductal adenocarcinoma (PDAC) with liver or lung-specific metastatic potentials induce different methylation and metabolic gene expression in cancer-associated fibroblasts (CAFs), affecting CAF phenotypes. CAFs from liver metastasis showed a more homogeneous phenotype, while CAFs from lung metastasis maintained heterogeneity.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Paweena Dana, Nutthanit Thumrongsiri, Prattana Tanyapanyachon, Walailuk Chonniyom, Primana Punnakitikashem, Nattika Saengkrit
Summary: Colorectal cancer is a tumor rich in cancer-associated fibroblast (CAF). CAF promotes cancer cell proliferation, metastasis, and drug resistance through the secretion of soluble factors and extracellular matrices, resulting in a dense stroma that hinders drug delivery. Resveratrol, a polyphenolic compound with anti-inflammatory and anticancer effects, was loaded into liposomes (L-RES) to inhibit CAF functions.
Article
Gastroenterology & Hepatology
Makoto Sano, Ryota Takahashi, Hideaki Ijichi, Kazunaga Ishigaki, Tomoharu Yamada, Koji Miyabayashi, Gen Kimura, Suguru Mizuno, Hiroyuki Kato, Hiroaki Fujiwara, Takuma Nakatsuka, Yasuo Tanaka, Jinsuk Kim, Yohei Masugi, Yasuyuki Morishita, Mariko Tanaka, Tetsuo Ushiku, Yousuke Nakai, Keisuke Tateishi, Yukimoto Ishii, Hiroyuki Isayama, Harold L. Moses, Kazuhiko Koike
Summary: PDAC is the deadliest cancer and frequently associated with CAT. This study found that inhibition of VCAM-1 can effectively treat PDAC and CAT in mice, leading to extended survival time. Increase of plasma ANP and sVCAM-1 may serve as diagnostic markers for CAT in PDAC.
Article
Oncology
Zikun Ma, Xiangdong Li, Yize Mao, Chen Wei, Zhuoli Huang, Guibo Li, Jianhua Yin, Xiaoyu Liang, Zhuowei Liu
Summary: In this study, a subset of cancer-associated fibroblasts (CAFs) characterized by overexpression of the urea transporter SLC14A1 was identified in bladder cancer patients. These CAFs were induced by interferon signaling and conferred stemness to bladder cancer cells through the WNT5A paracrine pathway. Inhibiting the formation of SLC14A1(+) CAFs sensitized tumor cells to chemotherapy. Importantly, bladder cancer patients with a high proportion of intratumoral SLC14A1(+) CAFs had a poor outcome and a worse response rate to neoadjuvant chemotherapy or immunotherapy.
Article
Biochemistry & Molecular Biology
Zhongwei Li, Pengfei Wang, Wenjie Cui, Hongmei Yong, Diandian Wang, Tiesuo Zhao, Wenwen Wang, Ming Shi, Junnian Zheng, Jin Bai
Summary: The study found that DNMT1 is overexpressed in breast cancer and promotes tumorigenesis and metastasis by activating its expression through ZEB1 and P300, and increasing its expression through the IL-6-pSTAT3-ZEB1-DNMT1 axis in the tumor microenvironment.
CELL AND BIOSCIENCE
(2022)
Article
Oncology
Amanda Fitzpatrick, Marjan Iravani, Adam Mills, Lucy Childs, Thanussuyah Alaguthurai, Angela Clifford, Isaac Garcia-Murillas, Steven Van Laere, Luc Dirix, Mark Harries, Alicia Okines, Nicholas C. Turner, Syed Haider, Andrew N. J. Tutt, Clare M. Isacke
Summary: This study uses ultra-low-pass whole genome sequencing (ulpWGS) to analyze cell-free DNA in cerebrospinal fluid and plasma, aiming to evaluate its potential in the diagnosis and therapy response monitoring of breast cancer leptomeningeal metastasis (BCLM). The results show that the level of ctDNA is highly consistent with the mutant allele fraction measured by tumor mutation-specific ddPCR assays, and monitoring the changes in ctDNA can predict the survival and clinical progression of BCLM.
CLINICAL CANCER RESEARCH
(2022)
Meeting Abstract
Oncology
Arany Soosainathan, Joanna Nikitorowicz-Buniak, Sunil Pancholi, Marjan Iravani, John Alexander, Syed Haider, Stephen R. Johnston, Mitchell Dowsett, Lesley A. Martin, Clare M. Isacke
Correction
Biochemistry & Molecular Biology
Max A. K. Ratze, Thijs Koorman, Thijmen Sijnesael, Blessing Bassey-Archibong, Robert van de Ven, Lotte Enserink, Daan Visser, Sridevi Jaksani, Ignacio Viciano, Elvira R. M. Bakker, Francois Richard, Andrew Tutt, Lynda O'Leary, Amanda Fitzpatrick, Pere Roca-Cusachs, Paul J. van Diest, Christine Desmedt, Juliet M. Daniel, Clare M. Isacke, Patrick W. B. Derksen
Article
Biochemistry & Molecular Biology
Max A. K. Ratze, Thijs Koorman, Thijmen Sijnesael, Blessing Bassey-Archibong, Robert van de Ven, Lotte Enserink, Daan Visser, Sridevi Jaksani, Ignacio Viciano, Elvira R. M. Bakker, Francois Richard, Andrew Tutt, Lynda O'Leary, Amanda Fitzpatrick, Pere Roca-Cusachs, Paul J. van Diest, Christine Desmedt, Juliet M. Daniel, Clare M. Isacke, Patrick W. B. Derksen
Summary: This study identifies the role of E-cadherin and Id2 in promoting the dormancy and dissemination of invasive lobular breast carcinoma (ILC) cells under anchorage-independent conditions.
Article
Oncology
Liam Jenkins, Ute Jungwirth, Alexandra Avgustinova, Marjan Iravani, Adam Mills, Syed Haider, James Harper, Clare M. Isacke
Summary: This study reveals that cancer-associated fibroblasts (CAF) can contribute to resistance to immune-checkpoint blockade therapy in breast cancer patients. High abundance of CAF is associated with an immunologically cold tumor microenvironment and decreased infiltration of CD8+ T cells. Additionally, the deletion of the CAF receptor Endo180 increases the infiltration of CD8+ T cells and enhances the sensitivity to immune-checkpoint blockade therapy.
Article
Oncology
Marta J. Llorca-Cardenosa, Lauren I. Aronson, Dragomir B. Krastev, Jadwiga Nieminuszczy, John Alexander, Feifei Song, Malgorzata Dylewska, Ronan Broderick, Rachel Brough, Astrid Zimmermann, Frank T. Zenke, Bora Gurel, Ruth Riisnaes, Ana Ferreira, Theodoros Roumeliotis, Jyoti Choudhary, Stephen J. Pettitt, Johann de Bono, Andres Cervantes, Syed Haider, Wojciech Niedzwiedz, Christopher J. Lord, Irene Y. Chong
Summary: The study highlights the potential issue of drug resistance in using ATR inhibitors in gastric cancer, particularly with loss-of-function mutations in SMG8 and SMG9, and suggests that targeting these pathways may enhance the overall effectiveness of ATRi.
Article
Oncology
Elizabeth R. Tucker, Irene Jimenez, Lindi Chen, Angela Bellini, Chiara Gorrini, Elizabeth Calton, Qiong Gao, Harvey Che, Evon Poon, Yann Jamin, Barbara Martins Da Costa, Karen Barker, Sumana Shrestha, J. Ciaran Hutchinson, Simran Dhariwal, Angharad Goodman, Elaine Del Nery, Pierre Gestraud, Jaydutt Bhalshankar, Yasmine Iddir, Elnaz Saberi-Ansari, Alexandra Saint-Charles, Birgit Geoerger, Maria Eugenia Marques Da Costa, Cecile Pierre-Eugene, Isabelle Janoueix-Lerosey, Didier Decaudin, Fariba Nemati, Angel M. Carcaboso, Didier Surdez, Olivier Delattre, Sally L. George, Louis Chesler, Deborah A. Tweddle, Gudrun Schleiermacher
Summary: ALK-activating mutations are present in approximately 10% of neuroblastomas and ALK amplifications in a further 1%-2% of cases. Lorlatinib, a third-generation ALK inhibitor, is being considered as a treatment for children with ALK-aberrant neuroblastoma. Resistance to single-agent treatment has been reported, and combination therapies with chemotherapy or MDM2 inhibitor are being explored to improve treatment efficacy.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Rachel J. Evans, Douglas W. Perkins, Joanna Selfe, Anna Kelsey, Gavin P. Birch, Janet M. Shipley, Koen Schipper, Clare M. Isacke
MOLECULAR CANCER THERAPEUTICS
(2023)
Article
Oncology
Frances K. Turrell, Rebecca Orha, Naomi J. Guppy, Andrea Gillespie, Matthew Guelbert, Chris Starling, Syed Haider, Clare M. Isacke
Summary: Patients with estrogen receptor (ER)-positive breast cancer are at risk of metastatic relapse due to dormant disseminated tumor cells (DTCs) reawakening at secondary sites. Aging or fibrotic microenvironment promotes DTC proliferation and upregulates tumor cell Pdgfc expression, stimulating further stromal activation. This study suggests targeting PDGF-C signaling could limit metastatic relapse in ER+ breast cancer.
Review
Oncology
Carlotta Becherini, Luca Visani, Saverio Caini, Indrani S. Bhattacharya, Anna M. Kirby, Gustavo Nader Marta, Gilberto Morgan, Viola Salvestrini, Charlotte E. Coles, Javier Cortes, Giuseppe Curigliano, Evandro de Azambuja, Nadia Harbeck, Clare M. Isacke, Orit Kaidar-Person, Elisabetta Marangoni, Birgitte Offersen, Hope S. Rugo, Andrea Morandi, Matteo Lambertini, Philip Poortmans, Lorenzo Livi, Icro Meattini
Summary: CDK4/6 inhibitors have become the standard treatment for HR+ and HER2- metastatic breast cancer, improving survival outcomes. Combining CDK4/6 inhibitors with endocrine therapy has shown significant benefits for high-risk HR+/HER2- early breast cancer. Each CDK4/6 inhibitor (palbociclib, ribociclib, and abemaciclib) has distinct toxicity profiles.
CANCER TREATMENT REVIEWS
(2023)
Article
Medicine, Research & Experimental
Angela M. Araujo, Andrea Abaurrea, Peio Azcoaga, Joanna Lopez-Velazco, Sara Manzano, Javier Rodriguez, Ricardo Rezola, Leire Egia-Mendikute, Fatima Valdes-Mora, Juana M. Flores, Liam Jenkins, Laura Pulido, Inaki Osorio-Querejeta, Patricia Fernandez-Nogueira, Nicola Ferrari, Cristina Viera, Natalia Martin-Martin, Alexandar Tzankov, Serenella Eppenberger-Castori, Isabel Alvarez-Lopez, Ander Urruticoechea, Paloma Bragado, Nicholas Coleman, Asis Palazon, Arkaitz Carracedo, David Gallego-Ortega, Fernando Calvo, Clare M. Isacke, Maria M. Caffarel, Charles H. Lawrie
Summary: This study reveals the pivotal role of the cytokine oncostatin M (OSM) in regulating interactions between immune and nonimmune stromal cells and epithelial cancer cells. It demonstrates that the stromal OSM/OSMR axis reprograms the tumor microenvironment and plays a key role in breast cancer progression.
JOURNAL OF CLINICAL INVESTIGATION
(2022)