Article
Oncology
T. L. Peters, T. Patil, A. T. Le, K. D. Davies, P. M. Brzeskiewicz, H. Nijmeh, L. Bao, D. R. Camidge, D. L. Aisner, R. C. Doebele
Summary: EGFR mutant non-small cell lung cancer patients initially respond well to EGFR-targeted therapy but often develop acquired resistance, which requires broad molecular testing to understand the resistance mechanisms and develop new treatment options.
NPJ PRECISION ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Rui Yan, Xuying Huang, Heshu Liu, Zeru Xiao, Jian Liu, Guangyu An, Yang Ge
Summary: For lung adenocarcinoma with EGFR-sensitive mutations, EGFR-TKI is the first-line treatment, but acquired resistance remains a problem. Reversing acquired resistance through targeting key molecules driving EMT provides an alternative for patients. This study explores the role of DCLK1 as an EMT driver gene in acquired resistance of lung adenocarcinoma to EGFR-TKIs.
Review
Oncology
Letian Zhang, David W. Goodrich
Summary: Lineage plasticity, the ability of cells to switch gene expression states, is crucial for tissue homeostasis and resistance to therapy. In cancer, lineage plasticity can lead to evasion of targeted therapies, becoming a growing clinical problem. This article presents key concepts and discusses therapeutic approaches to counter cancer lineage plasticity, with a focus on the role of oncogenic genetic mutations in driving this phenomenon.
ANNUAL REVIEW OF CANCER BIOLOGY
(2022)
Article
Oncology
Baoxia Zhao, Yan Zhang, Shen Lu, Mei Li
Summary: EGFR tyrosine kinase inhibitors have been successfully used in lung cancer treatment, but tumor cells may develop resistant phenotypes in the tumor microenvironment. In this study, two types of macrophage renewal were modeled and it was found that macrophage renewal modes may affect acquired resistance.
Article
Multidisciplinary Sciences
Paras Jain, Sophia Corbo, Kulsoom Mohammad, Sarthak Sahoo, Santhalakshmi Ranganathan, Jason T. George, Herbert Levine, Joseph Taube, Michael Toneff, Mohit Kumar Jolly
Summary: Epithelial-mesenchymal transition (EMT) and its reverse mesenchymal-epithelial transition (MET) play crucial roles in embryonic development, wound healing, and cancer metastasis. While short-term EMT induction can lead to reversible phenotypic changes, long-term EMT induction is often associated with irreversibility. In this study, we demonstrate that the phenotypic changes observed in MCF10A cells during long-term EMT induction by TGF-beta can in fact have longer timescales of reversibility. We also propose a mathematical model that explains how the epigenetic memory gained during long-term EMT induction can slow down the recovery to the epithelial state after TGF-beta withdrawal.
JOURNAL OF THE ROYAL SOCIETY INTERFACE
(2023)
Review
Oncology
Archana P. Thankamony, Ayalur Raghu Subbalakshmi, Mohit Kumar Jolly, Radhika Nair
Summary: Lineage plasticity, the ability of cells to transform from one lineage to another, is essential for tissue repair and homeostasis but can lead to tumor progression, relapse, and therapy resistance in cancer. This phenomenon can be triggered by treatment and has been observed across various solid and liquid tumors.
Article
Biochemistry & Molecular Biology
Jing Wang, Jingjing Li, Lijuan Yin, Tianjie Pu, Jing Wei, Varsha Karthikeyan, Tzu-Ping Lin, Allen C. Gao, Boyang Jason Wu
Summary: This study reveals that neuropilin 2 (NRP2) is upregulated in NEPC and plays a role in driving NEPC development and resistance. NRP2 interacts with AR to suppress AR signaling, and activates STAT3 phosphorylation by interacting with VEGFR2, promoting NEPC differentiation and growth.
Article
Oncology
Zhou Luan, Yoshihiro Morimoto, Atsushi Fushimi, Nami Yamashita, Wenhao Suo, Atrayee Bhattacharya, Masayuki Hagiwara, Caining Jin, Donald Kufe
Summary: MUC1-C drives the progression of PDAC by integrating IFN signaling and pluripotency with NE dedifferentiation, and may serve as a potential target for the treatment of poorly differentiated pancreatic NE carcinomas.
Article
Oncology
Adria Bernat-Peguera, Juan Navarro-Ventura, Laura Lorenzo-Sanz, Victoria da Silva-Diz, Mattia Bosio, Luis Palomero, Rosa M. Penin, Diana Perez Sidelnikova, Josep Oriol Bermejo, Miren Taberna, Noelia Vilarino, Josep M. Piulats, Ricard Mesia, Joan Maria Vinals, Eva Gonzalez-Suarez, Salvador Capella-Gutierrez, Alberto Villanueva, Francesc Vinals, Purificacion Munoz
Summary: EGFR-targeted therapy may be effective for treating cSCCs conserving epithelial traits, but resistance may occur in tumors with the E545K PIK3CA-activating mutation. Some initially responding tumors develop resistance after long-term treatment, induced by bypassing from EGFR signaling to FGFR signaling. Pharmacologic inhibition of FGFR signaling can overcome resistance to EGFR inhibitors.
CLINICAL CANCER RESEARCH
(2021)
Review
Endocrinology & Metabolism
William K. Storck, Allison M. May, Thomas C. Westbrook, Zhi Duan, Colm Morrissey, Joel A. Yates, Joshi J. Alumkal
Summary: The androgen receptor (AR) signaling pathway plays a critical role in the growth and differentiation of prostate cancer cells. Androgen deprivation therapy is the main treatment for metastatic prostate cancer, but resistance to AR signaling inhibitors is common. Lineage plasticity, specifically the switch to an alternate differentiation program, is a recently identified resistance mechanism. This review discusses the role of AR pathway loss and activation of a neuronal differentiation program in lineage plasticity, and explores new epigenetic therapeutic strategies to reverse this process.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Respiratory System
Junjie Chen, Lin Shi, Yao Qian, Yi Jin, Nian Dong, Chengshui Chen, Beibei Wang
Summary: This study identified that osteopontin (OPN) is involved in the development of EGFR-TKI resistance in NSCLC through the activation of the PI3K/AKT-EMT pathway. Inhibition of OPN expression and the PI3K/AKT signaling pathway significantly improved the sensitivity of EGFR-TKIs.
JOURNAL OF THORACIC DISEASE
(2023)
Article
Oncology
Sarah M. Pearsall, Stuart C. Williamson, Sam Humphrey, Ellyn Hughes, Derrick Morgan, Fernando J. Garcia Marques, Griselda Awanis, Rebecca Carroll, Laura Burks, Yan Ting Shue, Abel Bermudez, Kristopher K. Frese, Melanie Galvin, Mathew Carter, Lynsey Priest, Alastair Kerr, Cong Zhou, Trudy G. Oliver, Jonathan D. Humphries, Martin J. Humphries, Fiona Blackhall, Ian G. Cannell, Sharon J. Pitteri, Gregory J. Hannon, Julien Sage, Caroline Dive, Kathryn L. Simpson
Summary: This study investigates the phenotype and molecular mechanisms of vasculogenic mimicry (VM) in small cell lung cancer (SCLC) using circulating tumor cell-derived explant (CDX) models and genetically engineered mouse models (GEMMs). The results show that VM vessels are present in CDX models, GEMMs, and SCLC patient biopsies, and perfused VM vessels support tumor growth. Only NOTCH-active non-NE cells are VM-competent and exhibit characteristics related to blood vessel development and extracellular matrix organization. On Matrigel, VM-primed non-NE cells remodel the extracellular matrix into hollow tubules through an integrin b1-dependent process.
JOURNAL OF THORACIC ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Paras Jain, Sugandha Bhatia, Erik W. Thompson, Mohit Kumar Jolly
Summary: Phenotypic heterogeneity is a hallmark of aggressive cancer behavior and a clinical challenge. This study suggests that fluctuations or noise in content duplication and partitioning of the SNAIL gene during cell division can explain spontaneous phenotypic switching and dynamic heterogeneity in PMC42-LA cells.
Article
Cell Biology
Wen Jia, Mohit Kumar Jolly, Herbert Levine
Summary: The epithelial-mesenchymal transition (EMT) is a crucial cellular process for wound healing, cancer metastasis, and embryonic development. Recent studies have shown that hybrid epithelial/mesenchymal states, possessing both epithelial and mesenchymal traits, play a significant role in cancer metastasis and resistance to therapies. NRF2 has been identified as a stabilizing factor for these hybrid states. This research incorporates a phenomenological epigenetic feedback effect into a computational model for EMT signaling and demonstrates its stabilizing effect on the hybrid state if NRF2 influences SNAIL at an epigenetic level.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Oncology
Jiyun Lee, Zofia Piotrowska, Ross Soo, Byoung Chul Cho, Sun Min Lim
Summary: This article thoroughly reviews the current understanding of osimertinib resistance mechanisms and explores the established and emerging treatment options. It discusses new treatment strategies targeting resistance mechanisms, both EGFR-dependent and -independent, as well as novel approaches using bispecific antibodies and antibody-drug conjugates. The article also addresses the management of brain only progression and the incorporation of immunotherapy in EGFR-mutant lung cancer. Future perspectives on ongoing clinical trials and the combination of front-line therapy are introduced.
THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY
(2022)
Article
Oncology
Robert A. Parise, Julie L. Eiseman, Dana M. Clausen, Kimberly P. Kicielinski, Pamela A. Hershberger, Merrill J. Egorin, Jan H. Beumer
CANCER CHEMOTHERAPY AND PHARMACOLOGY
(2015)
Article
Oncology
Sarah A. Mazzilli, Pamela A. Hershberger, Mary E. Reid, Paul N. Bogner, Kristopher Atwood, Donald L. Trump, Candace S. Johnson
CANCER PREVENTION RESEARCH
(2015)
Article
Oncology
Alissa R. Verone-Boyle, Suzanne Shoemaker, Kristopher Attwood, Carl D. Morrison, Andrew J. Makowski, Sebastiano Battaglia, Pamela A. Hershberger
Article
Physiology
Andrew D. Ray, Kirkwood E. Personius, David L. Williamson, Cory M. Dungan, Samjot S. Dhillon, Pamela A. Hershberger
JOURNAL OF APPLIED PHYSIOLOGY
(2016)
Article
Substance Abuse
Noel J. Leigh, Ralph I. Lawton, Pamela A. Hershberger, Maciej L. Goniewicz
Article
Dentistry, Oral Surgery & Medicine
V. K. Vincent-Chong, H. DeJong, L. J. Rich, A. Patti, M. Merzianu, P. A. Hershberger, M. Seshadri
JOURNAL OF DENTAL RESEARCH
(2018)
Article
Medicine, Research & Experimental
Chang Liu, Tatiana Shaurova, Suzanne Shoemaker, Martin Petkovich, Pamela A. Hershberger, Yun Wu
MOLECULAR PHARMACEUTICS
(2018)
Article
Oncology
Brittany L. Bunch, Yingyu Ma, Kristopher Attwood, Lauren Amable, Wei Luo, Carl Morrison, Khurshid A. Guru, Anna Woloszynska-Read, Pamela A. Hershberger, Donald L. Trump, Candace S. Johnson
Article
Oncology
Vui King Vincent-Chong, Hendrik DeJong, Kristopher Attwood, Pamela A. Hershberger, Mukund Seshadri
Article
Biochemistry & Molecular Biology
Aparajita Verma, Vui King Vincent-Chong, Hendrik DeJong, Pamela A. Hershberger, Mukund Seshadri
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2020)
Article
Oncology
Tatiana Shaurova, Grace K. Dy, Sebastiano Battaglia, Alan Hutson, Letian Zhang, Yunkai Zhang, Christine M. Lovly, Mukund Seshadri, David W. Goodrich, Candace S. Johnson, Pamela A. Hershberger
Review
Nutrition & Dietetics
Zeinab Farhat, Pamela A. Hershberger, Jo L. Freudenheim, Manoj J. Mammen, Rachael Hageman Blair, Diana S. Aga, Lina Mu
Summary: Garlic's organosulfur compounds have potent anticancer properties, inhibiting carcinogenesis through various mechanisms such as apoptosis induction and antioxidant activity. Consumption of garlic is associated with decreased risk of colorectal cancer, while further studies are needed to clarify its effects on other types of cancer and the factors influencing the potency of garlic compounds.
EUROPEAN JOURNAL OF NUTRITION
(2021)
Review
Oncology
Erik S. Knudsen, Steven C. Pruitt, Pamela A. Hershberger, Agnieszka K. Witkiewicz, David W. Goodrich
Article
Oncology
Ronald Stoller, John C. Schmitz, Fei Ding, Shannon Puhalla, Chandra P. Belani, Leonard Appleman, Yan Lin, Yixing Jiang, Salah Almokadem, Daniel Petro, Julianne Holleran, Brian F. Kiesel, R. Ken Czambel, Benedito A. Carneiro, Emmanuel Kontopodis, Pamela A. Hershberger, Madani Rachid, Alice Chen, Edward Chu, Jan H. Beumer
CANCER CHEMOTHERAPY AND PHARMACOLOGY
(2017)