Article
Cell Biology
Qianzhi Chen, Qingyi Hu, Yan Chen, Na Shen, Ning Zhang, Anshu Li, Lei Li, Junjun Li
Summary: This study highlights the crucial role of PRMT6-mediated STAT3 R729me2a in breast cancer metastasis, revealing that PRMT6 positively regulates breast cancer metastasis through its effect on STAT3. Furthermore, the study identifies STAT3 R729me2a as a robust prognostic marker for predicting overall survival time in breast cancer patients. Additionally, the PRMT6 inhibitor EPZ020411 demonstrates significant potential in curbing breast cancer metastasis.
CELL DEATH & DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Anderly C. Chueh, Gahana Advani, Momeneh Foroutan, Jai Smith, Nadia Ng, Harshal Nandurkar, Daisy S. Lio, Hong-Jian Zhu, Yuh-Ping Chong, Heather Verkade, Donald J. Fujita, Jeffrey Bjorge, Faiza Basheer, Jet Phey Lim, Ian Luk, Amardeep Dhillon, Anuratha Sakthianandeswaren, Dmitri Mouradov, Oliver Sieber, Frederic Hollande, John M. Mariadason, Heung-Chin Cheng
Summary: The study reveals that downregulation of CHK/MATK expression in CRC cells is associated with promoter hypermethylation, leading to hyperactivation of SFKs and enhanced tumorigenic activity. Restoring CHK/MATK expression reduces SFK activity, inhibiting proliferation and migration of colorectal cancer cells in vitro and in vivo.
Article
Biochemistry & Molecular Biology
Natasha S. Clayton, Millie Fox, Jose J. Vicente-Garcia, Courtney M. Schroeder, Trevor D. Littlewood, Jonathon Wilde, Kadalmani Krishnan, Murray J. B. Brown, Claire Crafter, Helen R. Mott, Darerca Owen
Summary: Activated Cdc42-associated kinase (ACK) phosphorylates PI3K regulatory subunits, promoting cell proliferation. ACK interacts with p85 alpha in nuclear-enriched cell fractions, facilitating dimerization of the regulatory subunits.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Review
Oncology
Juan Luo, Hailin Zou, Yibo Guo, Tongyu Tong, Liping Ye, Chengming Zhu, Liang Deng, Bo Wang, Yihang Pan, Peng Li
Summary: Breast cancer is the most common malignant tumor worldwide and a leading cause of cancer-related deaths among women. SRC family kinases (SFKs), a type of non-receptor tyrosine kinase, have been found to play crucial roles in breast cancer progression. This review provides an overview of SRC kinase and its relevant functions in various subtypes of breast cancer, and highlights the role of SRC-mediated substrate phosphorylation in breast cancer signaling transductions. Furthermore, the progress of SRC-based targeted therapies and potential future directions in breast cancer are discussed.
BREAST CANCER RESEARCH
(2022)
Article
Biotechnology & Applied Microbiology
Ying Wu, Zhe Wang, Lu Han, Zhihao Guo, Bohua Yan, Lili Guo, Huadong Zhao, Mengying Wei, Niuniu Hou, Jing Ye, Zhe Wang, Changhong Shi, Suling Liu, Ceshi Chen, Suning Chen, Ting Wang, Jun Yi, JianPing Zhou, Libo Yao, Wenxia Zhou, Rui Ling, Jian Zhang
Summary: Cancer cells regulate their response to the chemotherapeutic drug doxorubicin through RNA m6A modification. They do this by inhibiting RNA m6A modification through PRMT5 and enhancing the nuclear translocation of the demethylase ALKBH5. This leads to increased DNA repair ability and decreased efficacy of doxorubicin. The approved drug tadalafil was identified as a PRMT5 inhibitor that could enhance doxorubicin sensitivity in breast cancer cells by decreasing RNA m6A methylation.
Article
Chemistry, Medicinal
Michel F. Sanner, Khalid Zoghebi, Samara Hanna, Saghar Mozaffari, Simin Rahighi, Rakesh K. Tiwari, Keykavous Parang
Summary: The cyclic peptide [WR](9) has been identified as a potent tyrosine kinase inhibitor, exhibiting higher inhibitory activity than other peptides against a variety of selected protein kinases. Molecular dynamics simulations suggest that [WR](9) affects the plasticity of the protein and the volume of the ATP binding site pocket, potentially contributing to its increased affinity.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Medicine, Research & Experimental
Ipshita Nandi, Harvey W. Smith, Virginie Sanguin-Gendreau, Linjia Ji, Alain Pacis, Vasilios Papavasiliou, Dongmei Zuo, Stella Nam, Sherif S. Attalla, Sung Hoon Kim, Sierra Lusson, Hellen Kuasne, Anne -Marie Fortier, Paul Savage, Constanza Martinez Ramirez, Morag Park, John A. Katzenellenbogen, Benita S. Katzenellenbogen, William J. Muller
Summary: Activation of c-Src promotes breast cancer progression by phosphorylating FOXM1 on 2 tyrosine residues, stimulating its nuclear localization and target gene expression. The positive feedback loop formed by c-Src and FOXM1 drives proliferation in luminal B-like breast cancer. Targeting this mechanism induces cell-cycle arrest, apoptosis, and blocks tumor progression in luminal breast cancers.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Biology
Li-Ming Liu, Qiang Tang, Xin Hu, Jing-Jing Zhao, Yuan Zhang, Guo-Guang Ying, Fei Zhang
Summary: PRMT1 serves as a key regulator of p53 function in breast cancer cells, inhibiting the transcriptional activity of p53 and affecting cell growth and senescence. Inhibition of PRMT1 with specific inhibitors can significantly weaken p53 signals and impede cell growth in breast cancer cells, highlighting the important role of PRMT1 in breast tumorigenesis.
Article
Biochemistry & Molecular Biology
Qin Wu, David Y. Nie, Wail Ba-alawi, YiShuai Ji, ZiWen Zhang, Jennifer Cruickshank, Jillian Haight, Felipe E. Ciamponi, Jocelyn Chen, Shili Duan, Yudao Shen, Jing Liu, Sajid A. Marhon, Parinaz Mehdipour, Magdalena M. Szewczyk, Nergiz Dogan-Artun, WenJun Chen, Lan Xin Zhang, Genevieve Deblois, Panagiotis Prinos, Katlin B. Massirer, Dalia Barsyte-Lovejoy, Jian Jin, Daniel D. De Carvalho, Benjamin Haibe-Kains, XiaoJia Wang, David W. Cescon, Mathieu Lupien, Cheryl H. Arrowsmith
Summary: This study identified an inhibitor called MS023 that has antitumor growth activity in triple-negative breast cancer (TNBC). Activation of interferon responses was found to be a functional biomarker and determinant of response in TNBC cell lines and human-derived organoids. Inhibition of type I PRMT triggers an interferon response through the antiviral defense pathway.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Medicine, Research & Experimental
Coralie Poulard, Thuy Ha Pham, Youenn Drouet, Julien Jacquemetton, Ausra Surmielova, Loay Kassem, Benoite Mery, Christine Lasset, Jonathan Reboulet, Isabelle Treilleux, Elisabetta Marangoni, Olivier Tredan, Muriel Le Romancer
Summary: Endocrine therapies targeting estrogen signaling have improved management of estrogen receptor alpha (ERα)-positive breast cancers. However, resistance to treatment remains a challenge. This study identifies nuclear PRMT5 expression as a predictive marker of sensitivity to tamoxifen in breast cancer patients, and reveals the mechanism of tamoxifen stimulating ERα methylation by PRMT5. This biomarker could be used to enhance response to tamoxifen in ERα-positive breast tumors.
EMBO MOLECULAR MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Lingxia Liu, Xiliu Zhang, Huayi Ding, Xin Liu, Donghui Cao, Yingqi Liu, Jiwei Liu, Cong Lin, Na Zhang, Guannan Wang, Jingyao Hou, Baiqu Huang, Yu Zhang, Jun Lu
Summary: This study uncovered a unique mechanism of controlling OXPHOS through arginine and lysine methylation, and highlighted the impact of the PRMT7-SETD6-MRPS23 axis during breast cancer metastasis.
Article
Cell Biology
Lian Zhang, Yujiao He, Yi Jiang, Qi Wu, Yanchen Liu, Qingqiang Xie, Yuxiu Zou, Jiaqian Wu, Chundong Zhang, Zhongjun Zhou, Xiu-Wu Bian, Guoxiang Jin
Summary: This study reveals the dual role of PRMT1-mediated RIP3 methylation in necroptotic cancer cell death and tumor immune escape. PRMT1 methylates RIP3 and inhibits its interaction with RIP1, thereby suppressing necrosome complex formation and necroptosis activation. The protein levels of PRMT1 and RIP3(ADMA) are positively correlated in cancer tissues and both serve as valuable prognostic markers for colon cancer.
CELL DEATH & DISEASE
(2023)
Article
Medicine, Research & Experimental
Cancan Lyu, Yuanchao Ye, Maddison M. Lensing, Kay-Uwe Wagner, Ronald J. Weigel, Songhai Chen
Summary: In HER2(+) breast cancer, overactivation of HER2 leads to aberrant G(i/o)-GPCR signaling, promoting cancer progression and resistance to HER2-targeted therapy. Pharmacologically deactivating GPCR signaling can block tumor growth and enhance therapeutic efficacy.
Article
Oncology
Chien-Hui Chan, Li-Wen Chiou, Tsai-Yu Lee, Yun-Ru Liu, Tsung-Han Hsieh, Ching-Yao Yang, Yung-Ming Jeng
Summary: The activation of PAK through cell-matrix interaction mediates resistance to sotorasib through the activation of MAPK and PI3K pathways.
BRITISH JOURNAL OF CANCER
(2023)
Article
Oncology
Xuemei Wang, Wenfang Xu, Chongyang Zhu, Yu Cheng, Jiemin Qi
Summary: PRMT7 is expressed at low levels in gastric cancer tissues and is associated with clinical characteristics. Functionally, PRMT7 inhibits proliferation and migration of gastric cancer cells. Mechanistically, PRMT7 suppresses PI3K/AKT signaling pathway activation by regulating PTEN. These findings suggest that PRMT7 may be a promising therapeutic target for gastric cancer.
Review
Endocrinology & Metabolism
Lucie Malbeteau, Ha Thuy Pham, Louisane Eve, Michael R. Stallcup, Coralie Poulard, Muriel Le Romancer
Summary: Steroid receptors (SRs) are important members of the nuclear hormonal receptor family, regulating various physiological functions essential for human health. Dysregulation of SRs may contribute to a wide range of pathologies, highlighting the significance of understanding their regulatory mechanisms.
Article
Oncology
Samyuktha Suresh, Solene Huard, Amelie Brisson, Fariba Nemati, Rayan Dakroub, Coralie Poulard, Mengliang Ye, Elise Martel, Cecile Reyes, David C. Silvestre, Didier Meseure, Andre Nicolas, David Gentien, Hussein Fayyad-Kazan, Muriel Le Romancer, Didier Decaudin, Sergio Roman-Roman, Thierry Dubois
Summary: This study identified PRMT1 as a potential therapeutic target for TNBC patients, as it is highly expressed in TNBC tumor samples and essential for breast cancer cell survival. Targeting PRMT1 in combination with chemotherapies may improve the survival outcome of TNBC patients.
Article
Oncology
Elsa Caumette, Antonio Di Meglio, Ines Vaz-Luis, Cecile Charles, Julie Havas, Garazi Ruiz de Azua, Elise Martin, Laurence Vanlemmens, Suzette Delaloge, Sibille Everhard, Anne-Laure Martin, Asma Dhaini Merimeche, Olivier Rigal, Charles Coutant, Marion Fournier, Christelle Jouannaud, Patrick Soulie, Paul-Henri Cottu, Olivier Tredan, Gwenn Menvielle, Agnes Dumas
Summary: The return to work after breast cancer recovery is influenced by psychosocial factors, including a shift in life values towards more emphasis on private life. Clinical determinants, work-related factors, and psychosocial factors all play a role in this change. Depressive symptoms are negatively associated with this shift.
JOURNAL OF CANCER SURVIVORSHIP
(2023)
Article
Oncology
Florence Oberkampf, Maya Gutierrez, Olfa Trabelsi Grati, Emilie Le Rhun, Olivier Tredan, Isabelle Turbiez, Amir Kadi, Coraline Dubot, Sophie Taillibert, Sophie Vacher, Claire Bonneau
Summary: This study aimed to evaluate the efficacy of intrathecal trastuzumab in HER2 + BC patients with leptomeningeal metastasis. The results showed that weekly administration of 150 mg of intrathecal trastuzumab was effective in controlling neurological progression.
Article
Oncology
Hope S. Rugo, Aditya Bardia, Frederik Marme, Javier Cortes, Peter Schmid, Delphine Loirat, Olivier Tredan, Eva Ciruelos, Florence Dalenc, Patricia Gomez Pardo, Komal L. Jhaveri, Rosemary Delaney, Olivia Fu, Lanjia Lin, Wendy Verret, Sara M. Tolaney
Summary: The study demonstrates the potential of Sacituzumab govitecan in the treatment of breast cancer, with a longer progression-free survival compared to traditional chemotherapy regimens and a manageable safety profile.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Health Care Sciences & Services
Elise Bonnet, Veronique Haddad, Stanislas Quesada, Kim-Arthur Baffert, Audrey Lardy-Cleaud, Isabelle Treilleux, Daniel Pissaloux, Valery Attignon, Qing Wang, Adrien Buisson, Pierre-Etienne Heudel, Thomas Bachelot, Armelle Dufresne, Lauriane Eberst, Philippe Toussaint, Valerie Bonadona, Christine Lasset, Alain Viari, Emilie Sohier, Sandrine Paindavoine, Valerie Combaret, David Perol, Isabelle Ray-Coquard, Jean-Yves Blay, Olivier Tredan
Summary: This study analyzed the alterations in homologous recombination-related genes in metastatic triple-negative breast cancer (mTNBC) patients and found that mutations in HRR genes and epimutations in RAD51C were associated with platinum sensitivity. Apart from mutations in BRCA1/2 genes, a more comprehensive evaluation of HRD should be considered to select patients who could benefit from platinum-based chemotherapy.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Oncology
Olivier Tredan, Caroline Robert, Antoine Italiano, Fabrice Barlesi
Summary: Genome-wide testing plays a crucial role in advancing precision medicine in oncology; however, current recommendations lack specificity regarding its indications and utility for different types of cancer. To address this, a national consensus approach using a modified Delphi methodology was employed in France to provide expert opinions on the use of genome-wide testing in clinical practice. Consensus was reached through multiple rounds of rating, resulting in 24 statements agreed upon by the expert panel. While genome-wide testing was recommended for non-small cell lung cancer (NSCLC) and cancer of unknown primary (CUP), its routine use was not recommended for breast cancer and melanoma. The standardization of broad molecular screening in oncology may be facilitated by improved access to innovation in France.
BULLETIN DU CANCER
(2023)
Article
Oncology
Idlir Licaj, Elodie Coquan, Tienhan Sandrine Dabakuyo-Yonli, Sarah Dauchy, Ines Vaz Luis, Cecile Charles, Cedric Lemogne, Olivier Tredan, Laurence Vanlemmens, Christelle Jouannaud, Christelle Levy, Olivier Rigal, Marion Fournier, Thierry Petit, Florence Dalenc, Philippe Rouanet, Jerome Lemonnier, Sibille Everhard, Paul Cottu, Florence Joly
Summary: This study used the CANTO cohort to study the associations between baseline quality of life and chemotherapy dose-reductions (CDRs) or post-chemotherapy toxicities (PCTs). The results showed that baseline physical functioning and fatigue were associated with CDRs and PCTs.
Article
Oncology
Pauline Corbaux, Catherine Terret, Claire Cropet, Sylvie Chabaud, Chiara Russo, Christelle Faure, Olivier Tredan, Thomas Bachelot, Pierre-Etienne Heudel
Summary: This study aimed to examine the effect of additional chemotherapy on overall survival in patients aged 70 years or older with early breast cancer, as well as the impact of comorbidities on chemotherapy benefit. The results showed that additional chemotherapy was associated with improved overall survival, while chronic obstructive pulmonary disease and polypharmacy were associated with worse overall survival. These findings support the importance of chemotherapy considerations in elderly patients with early breast cancer.
INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Gisele Chvetzoff, Carole Bouleuc, Audrey Lardy-Cleaud, Pierre Saltel, Veronique Dieras, Magali Morelle, Jean-Paul Guastalla, Olivier Tredan, Paul Rebattu, Simona Pop, Isabelle Ray-Coquard, Jean-Yves Pierga, Laurent Mignot, Valerie Laurence, Valerie Bourne-Branchu, David Perol, Thomas Bachelot
Summary: This study compared the impact of early palliative care and usual oncology care on the decision for additional chemotherapy. The results showed no significant difference in the prescription rate of chemotherapy between the two groups, but the early palliative care group had less deterioration in physical functioning and improved information exchange and communication.
SUPPORTIVE CARE IN CANCER
(2023)
Article
Oncology
Houssein El Hajj, Domenico Ferraioli, Pierre Meus, Frederic Beurrier, Olivier Tredan, Isabelle Ray-Coquard, Nicolas Chopin
Summary: ObjectiveSplenectomy is performed in a significant percentage of cytoreductive surgeries for ovarian cancer. This study aimed to evaluate the impact of splenectomy on overall and disease-free survival in patients with epithelial ovarian cancer. MethodsA retrospective study was conducted on patients who underwent cytoreduction for ovarian cancer between January 2000 and December 2016. Patients were stratified into splenectomy and non-splenectomy groups, and postoperative complications and survival outcomes were analyzed. ResultsA total of 464 patients were included in the study. The splenectomy group had higher disease stages, peritoneal carcinomatosis scores, and radical surgery rates. However, there was no significant difference in complete cytoreduction rates between the two groups. Splenectomy was associated with extensive surgical procedures and increased risk of abdominopelvic lymphocele and blood transfusion. The average length of hospital stay and delay in adjuvant chemotherapy were longer in the splenectomy group. Overall and disease-free survival rates were not significantly different between the groups. ConclusionSplenectomy may be a safe procedure with no impact on overall or disease-free survival in patients with ovarian cancer. However, it is associated with longer hospital stay and delay in chemotherapy.
INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
(2023)
Article
Multidisciplinary Sciences
Andrea Alegre-Marti, Alba Jimenez-Panizo, Adrian Martinez-Tebar, Coralie Poulard, M. Nuria Peralta-Moreno, Montserrat Abella, Rosa Anton, Marcos Chinas, Ulrich Eckhard, Josep M. Piulats, Ana M. Rojas, Juan Fernandez-Recio, Jaime Rubio-Martinez, Muriel Le Romancer, Alvaro Aytes, Pablo Fuentes-Prior, Eva Estebanez-Perpina
Summary: This study reveals that mutations of the androgen receptor (AR) associated with prostate cancer and androgen insensitivity syndrome can influence its structure and function, leading to altered transcription signatures and drug responses. These mutations induce an allosteric switch in the AR ligand-binding domain (AR-LBD), increasing exposure of a key methylation target and impacting AR-dependent transcription and response to anti-androgens. These findings have implications for precision medicine and understanding disease mechanisms.
Article
Oncology
Khalil Hodroj, David Pellegrin, Cindy Menard, Thomas Bachelot, Thierry Durand, Philippe Toussaint, Armelle Dufresne, Benoite Mery, Olivier Tredan, Thibaut Goulvent, Pierre Heudel
Summary: This study describes the implementation of an MDT application prototype based on structured data for ABC MDT meetings, which improved the quality and confidence of clinical decisions, and could support sustained improvements to patient care.
Meeting Abstract
Oncology
Ouissam Al Jarroudi, Coralie Williams, Rita Santos, Armelle Dufresne, Valery Attignon, Anthony Ferrari, Sandrine Boyault, Laurie Tonon, Severine Tabone-Eglinger, Philippe Alexandre Cassier, Nadege Carradini, Armelle Vinceneux, Aurelie Swalduz, Alain Viari, Sylvie Chabaud, David Perol, Mohammad Afshar, Jean-Yves Blay, Olivier Tredan, Pierre Saintigny
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Geriatrics & Gerontology
Claire Falandry, Fanny Pommeret, Laurence Gladieff, Fabien Tinquaut, Domenico Lorusso, Marie-Ange Mouret-Reynier, Veronique D'Hondt, Delphine Mollon-Grange, Anne Floquet, Sophie Abadie-Lacourtoisie, Pierre-Emmanuel Brachet, Laetitia Stefani, Frederique Rousseau, Jean-Sebastien Frenel, Francesco Del Piano, Marja Komulainen, Thomas Warkus, Olivier Tredan, Eric Pujade-Lauraine, Gilles Freyer
Summary: This study aimed to validate the geriatric vulnerability score (GVS), developed by a group of French investigators, in predicting outcomes in ovarian cancer patients. The results showed that the GVS had a good prognostic performance for overall survival in advanced ovarian cancer patients, regardless of geographic and historic effect as well as treatment patterns. It could provide a promising approach for stratifying populations in clinical research.
LANCET HEALTHY LONGEVITY
(2022)