Review
Biochemistry & Molecular Biology
Farah Raheem, Suganya Arunachalam Karikalan, Felipe Batalini, Aya El Masry, Lida Mina
Summary: Endocrine therapy is the primary treatment for hormone receptor-positive breast cancer. However, advanced tumors often develop resistance to this therapy, which can be caused by alterations in the estrogen receptor pathway or upstream growth factor signaling pathways. Despite progress in this field, resistance remains a major limitation and challenge.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Aditya Bardia, Sarat Chandarlapaty, Hannah M. Linden, Gary A. Ulaner, Alice Gosselin, Sylvaine Cartot-Cotton, Patrick Cohen, Severine Doroumian, Gautier Paux, Marina Celanovic, Vasiliki Pelekanou, Jeffrey E. Ming, Nils Ternes, Monsif Bouaboula, Joon Sang Lee, Anne-Laure Bauchet, Mario Campone
Summary: The study evaluates the safety and antitumor activity of amcenestrant as monotherapy in postmenopausal women with ER+/HER2- advanced breast cancer. The results show that amcenestrant is well-tolerated and demonstrates preliminary antitumor activity, suggesting its potential clinical utility.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Lixuan Wei, Huanyao Gao, Jia Yu, Huan Zhang, Thanh Thanh L. Nguyen, Yayun Gu, Marie R. Passow, Jodi M. Carter, Bo Qin, Judy C. Boughey, Matthew P. Goetz, Richard M. Weinshilboum, James N. Ingle, Liewei Wang
Summary: Androgen receptor (AR) is expressed in the majority of estrogen receptor a-positive (ER+) breast cancers. The efficacy of AR-targeting therapies, including both AR agonists and AR inhibitors, is dependent on the levels of AR and ERa. ENZ functions as an ERa antagonist in low AR expression breast cancer, while RAD140 activates AR signaling and suppresses AR-high tumor growth. Overall, this study provides insights into the clinical application of AR-targeting therapy based on the AR/ER ratio in ER+ breast cancers.
Article
Oncology
Karen Page, Luke J. Martinson, Daniel Fernandez-Garcia, Allison Hills, Kelly L. T. Gleason, Molly C. Gray, Amelia J. Rushton, Georgios Nteliopoulos, Robert K. Hastings, Kate Goddard, Charlotte Ions, Vilas Parmar, Lindsay Primrose, Mark R. Openshaw, David S. Guttery, Carlo Palmieri, Simak Ali, Justin Stebbing, R. Charles Coombes, Jacqueline A. Shaw
Summary: The study found that ctDNA could be detected across the spectrum of breast cancer, particularly in MBC where variants in ESR1, TP53, and PIK3CA predicted poor overall survival. The assay could be used to monitor the emergence of resistance mutations, such as those in ESR1, which signify resistance to aromatase inhibitors and help tailor adjuvant therapies. However, caution is advised when interpreting results from a single plasma sample as variants were also detected in a small proportion of healthy controls.
JCO PRECISION ONCOLOGY
(2021)
Article
Chemistry, Medicinal
Yunlong Lu, Chao Liu, Xin Wang, Lijuan Liu, Zhihao Zhao, Zhenlin Liang, Yuanhao Liu, Zhenfan Wen, Qianming Du, Wukun Liu
Summary: Although endocrine therapies have shown good responses in ER+ breast cancer patients, drug resistance remains an issue. Researchers developed a new class of orally bioavailable fluorine-substituted SERDs, one of which (27b) shows excellent pharmacokinetic profiles and potential as an orally available SERD for clinical use.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Oncology
Sarat Chandarlapaty, Maura N. Dickler, Jose Alejandro Perez Fidalgo, Rafael Villanueva-Vazquez, Jennifer Giltnane, Mary Gates, Ching-Wei Chang, Sravanthi Cheeti, Jill Fredrickson, Xiaojing Wang, Ann Collier, Heather M. Moore, Ciara Metcalfe, Jennifer Lauchle, Eric W. Humke, Aditya Bardia
Summary: GDC-0927 is a novel, potent, nonsteroidal, orally administered drug for the treatment of static breast cancer. The study demonstrated that GDC-0927 is well tolerated, with pharmacokinetics supporting once-daily dosing, and has a certain degree of antitumor activity in breast cancer.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Saya Jacob, Andrew A. Davis, Lorenzo Gerratana, Marko Velimirovic, Ami N. Shah, Firas Wehbe, Neelima Katam, Qiang Zhang, Lisa Flaum, Kalliopi P. Siziopikou, Leonidas C. Platanias, William J. Gradishar, Amir Behdad, Aditya Bardia, Massimo Cristofanilli
Summary: The study analyzed serial ctDNA samples to characterize genomic evolution in progressive metastatic breast cancer, showing that increased NOA and MAF were associated with disease progression. Results suggest that prospective longitudinal ctDNA evaluation could potentially monitor tumor genomic evolution and detect resistance alterations. The study highlights the importance of ctDNA as a promising tool for noninvasive longitudinal monitoring of genomic alterations in breast cancer patients.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Sven Rosswag, Cristina L. Cotarelo, Klaus Pantel, Sabine Riethdorf, Jonathan P. Sleeman, Marcus Schmidt, Sonja Thaler
Summary: Acquired endocrine resistance and late recurrence in patients with ER+/HER2- breast cancer are complex and not fully understood. Circulating tumor cells (CTCs) from patients can provide insight into the mechanisms of acquired resistance and potential therapeutic approaches to combatting resistance.
Article
Oncology
Bora Lim, David A. Potter, Mohamad A. Salkeni, Paula Silverman, Tufia C. Haddad, Frederic Forget, Ahmad Awada, Jean-Luc Canon, Michael Danso, Alain Lortholary, Hugues Bourgeois, Elizabeth Tan-Chiu, Sylvie Vincent, Brittany Bahamon, Kevin J. Galinsky, Chirag Patel, Rachel Neuwirth, E. Jane Leonard, Jennifer R. Diamond
Summary: The study evaluated the efficacy and safety of sapanisertib plus exemestane or fulvestrant in treating advanced/metastatic hormone receptor-positive breast cancer, showing certain clinical benefit for patients. The treatment demonstrated different efficacy in patients previously sensitive or resistant to exemestane.
CLINICAL CANCER RESEARCH
(2021)
Review
Oncology
Zsuzsanna Nagy, Rinath Jeselsohn
Summary: Breast cancer is the most common female malignant tumor and the leading cause of cancer death in women worldwide. Hormone receptor positive (ER+) breast cancer is the most common subtype, and current treatment includes targeting the estrogen receptor with endocrine therapy (ET). However, resistance to ET is a major challenge for ER+ breast cancer patients, leading to disease recurrence or progression.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
Alexej Ballhausen, Jennifer J. Wheler, Daniel D. Karp, Sarina A. Piha-Paul, Siqing Fu, Shubham Pant, Apostolia M. Tsimberidou, David S. Hong, Vivek Subbiah, Veronica R. Holley, Helen J. Huang, Abenaa M. Brewster, Kimberly B. Koenig, Nuhad K. Ibrahim, Funda Meric-Bernstam, Filip Janku
Summary: The combination therapy of everolimus, letrozole, and trastuzumab showed favorable safety profile and encouraging signs of anticancer activity in patients with heavily pretreated hormone receptor- and HER2-positive advanced cancers. Some patients, particularly those with HER2 amplification, had partial responses to the treatment.
CLINICAL CANCER RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Brent Y. Chick, Diana C. Hargreaves
Summary: Recent research reveals that the CoREST complex plays a crucial role in regulating the acquisition of endocrine therapy resistance in estrogen receptor-positive breast cancers. Profiling data demonstrate that this resistance transition is associated with the functional retargeting of CoREST on chromatin, which occurs in coordination with cJUN and SWI/SNF (cBAF).
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)
Article
Oncology
Michele L. LeNoue-Newton, Sheau-Chiann Chen, Thomas Stricker, David M. Hyman, Natalie Blauvelt, Philippe L. Bedard, Funda Meric-Bernstam, Rinaa S. Punglia, Deborah Schrag, Eva M. Lepisto, Fabrice Andre, Lillian Smyth, Semih Dogan, Celeste Yu, Chetna Wathoo, Mia Levy, Lisa D. Eli, Feng Xu, Grace Mann, Alshad S. Lalani, Fei Ye, Christine M. Micheel, Monica Arnedos
Summary: The purpose of this study was to investigate the prognosis and phenotypic characteristics of hormone receptor-positive advanced breast cancer tumors with an ERBB2 mutation in the absence of HER2 amplification. The results showed that the presence of an ERBB2 mutation did not affect overall survival or treatment response. However, some differences in coexisting mutations were observed between the ERBB2-mutated and control groups.
CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Belinda J. Petri, Kellianne M. Piell, Gordon C. South Whitt, Ali E. Wilt, Claire C. Poulton, Norman L. Lehman, Brian F. Clem, Matthew A. Nystoriak, Marcin Wysoczynski, Carolyn M. Klinge
Summary: The RNA binding protein and m6A reader HNRNPA2B1 is overexpressed in breast tumors compared to normal tissue. Overexpression of A2B1 leads to tamoxifen and fulvestrant resistance, while knockdown of A2B1 restores endocrine sensitivity. Targeting A2B1 could be a potential therapeutic strategy to overcome acquired endocrine resistance in breast cancer.
Article
Pharmacology & Pharmacy
Xiaodan Sun, Fen Tang, Qian Guo, Yiwen Liu, Yiqing He, Yan Du, Feng Gao, Guoliang Zhang, Cuixia Yang
Summary: The loss of hyaluronan synthase 2 (HAS2) may be related to the acquisition of endocrine resistance in estrogen receptor-positive (ER+) breast cancer, in which the upregulation of the membrane cytoskeletal protein EZ may play a key role. Inhibition of EZ can restore the sensitivity of endocrine-resistant cells to drug therapy.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Oncology
Hazel M. Weir, Robert H. Bradbury, Mandy Lawson, Alfred A. Rabow, David Buttar, Rowena J. Callis, Jon O. Curwen, Camila de Almeida, Peter Ballard, Michael Hulse, Craig S. Donald, Lyman J. L. Feron, Galith Karoutchi, Philip MacFaul, Thomas Moss, Richard A. Norman, Stuart E. Pearson, Michael Tonge, Gareth Davies, Graeme E. Walker, Zena Wilson, Rachel Rowlinson, Steve Powell, Claire Sadler, Graham Richmond, Brendon Ladd, Ermira Pazolli, Anne Marie Mazzola, Celina D'Cruz, Chris De Savi
Article
Oncology
Garrett W. Rhyasen, Maureen M. Hattersley, Yi Yao, Austin Dulak, Wenxian Wang, Philip Petteruti, Ian L. Dale, Scott Boiko, Tony Cheung, Jingwen Zhang, Shenghua Wen, Lillian Castriotta, Deborah Lawson, Michael Collins, Larry Bao, Miika J. Ahdesmaki, Graeme Walker, Greg O'Connor, Tammie C. Yeh, Alfred A. Rabow, Jonathan R. Dry, Corinne Reimer, Paul Lyne, Gordon B. Mills, Stephen E. Fawell, Michael J. Waring, Michael Zinda, Edwin Clark, Huawei Chen
MOLECULAR CANCER THERAPEUTICS
(2016)
Article
Oncology
Weiyi Toy, Hazel Weir, Pedram Razavi, Mandy Lawson, Anne U. Goeppert, Anne Marie Mazzola, Aaron Smith, Joanne Wilson, Christopher Morrow, Wai Lin Wong, Elisa De Stanchina, Kathryn E. Carlson, Teresa S. Martin, Sharmeen Uddin, Zhiqiang Li, Sean Fanning, John A. Katzenellenbogen, Geoffrey Greene, Jose Baselga, Sarat Chandarlapaty
Article
Oncology
James R. Bradford, Mark Wappett, Garry Beran, Armelle Logie, Oona Delpuech, Henry Brown, Joanna Boros, Nicola J. Camp, Robert McEwen, Anne Marie Mazzola, Celina D'Cruz, Simon T. Barry
Article
Oncology
Ryan E. Henry, Evan R. Barry, Lillian Castriotta, Brendon Ladd, Aleksandra Markovets, Garry Beran, Yongxin Ren, Feng Zhou, Ammar Adam, Michael Zinda, Corinne Reimer, Weiguo Qing, Weiguo Su, Edwin Clark, Celina M. D'Cruz, Alwin G. Schuller
Review
Physiology
Michael P. Collins, Michael Forgac
FRONTIERS IN PHYSIOLOGY
(2018)
Article
Biochemistry & Molecular Biology
Christina M. McGuire, Michael P. Collins, GeHong Sun-Wada, Yoh Wade, Michael Forgac
JOURNAL OF BIOLOGICAL CHEMISTRY
(2019)
Article
Biochemistry & Molecular Biology
Michael P. Collins, Laura A. Stransky, Michael Forgac
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Oncology
Theresa A. Proia, Maneesh Singh, Richard Woessner, Larissa Carnevalli, Gayathri Bommakanti, Lukasz Magiera, Srimathi Srinivasan, Shaun Grosskurth, Mike Collins, Chris Womack, Matthew Griffin, Minwei Ye, Susan Cantin, Deanna Russell, Mingchao Xie, Adina Hughes, Nanhua Deng, Deanna A. Mele, Stephen Fawell, Simon Barry, Corinne Reimer, J. Carl Barrett, Patricia McCoon
CLINICAL CANCER RESEARCH
(2020)
Article
Multidisciplinary Sciences
Kiran Musunuru, Alexandra C. Chadwick, Taiji Mizoguchi, Sara P. Garcia, Jamie E. DeNizio, Caroline W. Reiss, Kui Wang, Sowmya Iyer, Chaitali Dutta, Victoria Clendaniel, Michael Amaonye, Aaron Beach, Kathleen Berth, Souvik Biswas, Maurine C. Braun, Huei-Mei Chen, Thomas Colace, John D. Ganey, Soumyashree A. Gangopadhyay, Ryan Garrity, Lisa N. Kasiewicz, Jennifer Lavoie, James A. Madsen, Yuri Matsumoto, Anne Marie Mazzola, Yusuf S. Nasrullah, Joseph Nneji, Huilan Ren, Athul Sanjeev, Madeleine Shay, Mary R. Stahley, Steven H. Y. Fan, Ying K. Tam, Nicole M. Gaudelli, Giuseppe Ciaramella, Leslie E. Stolz, Padma Malyala, Christopher J. Cheng, Kallanthottathil G. Rajeev, Ellen Rohde, Andrew M. Bellinger, Sekar Kathiresan
Summary: This study demonstrates the efficient and precise modification of disease-related genes in living cynomolgus monkeys using CRISPR base editors delivered in vivo via lipid nanoparticles. The results provide proof-of-concept for the potential therapeutic application of CRISPR base editors in making precise single-nucleotide changes in target genes, supporting a 'once-and-done' approach for the treatment of diseases.
Article
Biochemical Research Methods
Ellen F. Vieux, Roman V. Agafonov, Lydia Emerson, Marta Isasa, Richard W. Deibler, Jeffrey R. Simard, David Cocozziello, Brendon Ladd, Linda Lee, Heng Li, Stephen Archer, Mark Fitzgerald, Ryan Michael, Christopher G. Nasveschuk, Eunice S. Park, Gunther Kern, David A. Proia, Andrew J. Phillips, Stewart L. Fisher
Summary: This work developed an in vitro system to measure the kinetics of BRD4 BD1 ubiquitination and characterized the affinities between BiDACs, BD1, and CRBN, providing a new tool for understanding and optimizing the catalytic and thermodynamic properties of BiDACs.
Article
Biochemistry & Molecular Biology
Kevin Su, Michael P. Collins, Christina M. McGuire, Mohammed A. Alshagawi, Mariam K. Alamoudi, Zhen Li, Michael Forgac
Summary: The a4 isoform of the V-ATPase plays a significant role in the migration and invasion of breast cancer cells, as well as in the growth of tumors in vivo. Targeting this isoform may represent a novel therapeutic strategy to limit breast cancer growth and metastasis.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)