Review
Pharmacology & Pharmacy
Sonali Mehendale-Munj, Shivangi Sawant
Summary: Breast Cancer Resistance Protein (BCRP) is an efflux transporter responsible for causing multidrug resistance. BCRP expels potent antineoplastic drugs, leading to resistance and failure in cancer treatment. The regulation and expression of BCRP play important roles in maintaining the balance of xenobiotics and nutrients, impacting cancer therapies.
CURRENT DRUG TARGETS
(2021)
Article
Oncology
Jihui Chen, Zhipeng Wang, Shouhong Gao, Kejin Wu, Fang Bai, Qiqiang Zhang, Hongyu Wang, Qin Ye, Fengjing Xu, Hong Sun, Yunshu Lu, Yan Liu
Summary: The study revealed that ABCC5 expression is associated with pemetrexed resistance, suggesting it may serve as a target or biomarker for optimizing pemetrexed regimens in breast cancer treatment.
CANCER CELL INTERNATIONAL
(2021)
Article
Biochemistry & Molecular Biology
Po-Jung Huang, Ching-Yun Huang, Yu-Xuan Li, Yi-Chung Liu, Lichieh-Julie Chu, Yuan-Ming Yeh, Wei-Hung Cheng, Ruei-Ming Chen, Chi-Ching Lee, Lih-Chyang Chen, Hsin-Chung Lin, Shu-Fang Chiu, Wei-Ning Lin, Ping-Chiang Lyu, Petrus Tang, Kuo-Yang Huang
Summary: Trichomonas vaginalis is the causative agent of trichomoniasis, a common sexually transmitted infection. Metronidazole (MTZ) is the main treatment, but drug resistance is a growing concern. RNA sequencing of MTZ-resistant and MTZ-sensitive strains revealed upregulation of drug-resistant genes and novel pathways related to drug-induced stress.
Article
Microbiology
Valentin Borgeat, Danielle Brandalise, Frederic Grenouillet, Dominique Sanglard
Summary: Candida lusitaniae is an opportunistic pathogen in humans that can rapidly acquire multidrug resistance, with the ABC transporter CDR1 playing an important role in azole resistance.
Article
Biochemistry & Molecular Biology
Chao-Yun Cai, Qiu-Xu Teng, Megumi Murakami, Suresh V. Ambudkar, Zhe-Sheng Chen, Vijaya L. Korlipara
Summary: A series of 22 quinazolinamine derivatives with potent inhibitory activities on BCRP and P-gp were synthesized. Compound 22 was identified as a dual BCRP and P-gp inhibitor, while compound 33 showed BCRP inhibitory activity. These compounds changed the localization of BCRP and P-gp, inhibiting the efflux of anticancer drugs by the two ABC transporters. Compounds 22 and 33 also stimulated ATP hydrolysis, increasing the accumulation of mitoxantrone in BCRP-overexpressing cells.
Article
Pharmacology & Pharmacy
Lucie Cermakova, Jakub Hofman, Lenka Lastovickova, Lucie Havlickova, Ivona Springrova, Eva Novotna, Vladimir Wsol
Summary: This study demonstrates that the Bruton's tyrosine kinase inhibitor Zanubrutinib can counteract anthracycline (ANT) drug resistance by targeting aldo-keto reductase 1C3 (AKR1C3) and ATP-binding cassette (ABC) transporters. Zanubrutinib inhibits AKR1C3-mediated inactivation of daunorubicin (DAUN) and interferes with the efflux of DAUN mediated by ABC transporters. These findings provide a rationale for including Zanubrutinib in ANT-based therapy and suggest its potential for treating tumors expressing AKR1C3 and/or ABC transporters.
Article
Biochemistry & Molecular Biology
Ingrid Fatima Zattoni, Thales Kronenberger, Diogo Henrique Kita, Lais Danciguer Guanaes, Matheus Murmel Guimaraes, Larissa de Oliveira Prado, Melanie Ziasch, Luis C. Vesga, Fabiane Gomes de Moraes Rego, Geraldo Picheth, Marcos Brown Goncalves, Miguel D. Noseda, Diogo R. B. Ducatti, Antti Poso, Robert W. Robey, Suresh Ambudkar, Vivian Rotuno Moure, Alan Guilherme Goncalves, Glaucio Valdameri
Summary: A newly discovered porphyrin derivative (4B) was identified as an inhibitor of the ABCG2 transporter, capable of overcoming multidrug resistance in vitro and showing selective inhibition towards ABCG2 without being transported by it.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Article
Pharmacology & Pharmacy
Chung-Pu Wu, Sung-Han Hsiao, Yu-Shan Wu
Summary: The overexpression of human ATP-binding cassette (ABC) transporters in cancer cells can lead to multidrug resistance (MDR), which poses a significant obstacle to chemotherapy. Currently, there are no approved drugs specifically designed to treat multidrug-resistant cancers. However, drug repurposing has emerged as a practical approach to discover effective modulators of drug transporters.
DRUG RESISTANCE UPDATES
(2023)
Article
Microbiology
Elizaveta O. O. Noskova, Olga V. V. Markova, Dmitry A. A. Knorre, Kseniia V. V. Galkina
Summary: In yeast, MDR transporters efflux xenobiotics from the cytoplasm to the environment and MDR genes are induced upon the accumulation of xenobiotics. Fungal cells can produce secondary metabolites similar to MDR transporter substrates. This study found that tyrosol, a secondary metabolite, induced MDR in yeast by inhibiting the efflux of MDR transporter substrate and also inhibited the cytostatic effect of clotrimazole.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Medicine, Research & Experimental
Jeon-Kyung Kim, Min Sun Choi, Jae-Young Kim, Jun Sang Yu, Jeong In Seo, Hye Hyun Yoo, Dong-Hyun Kim
Summary: Treatment with Gingko biloba leaf extract (GLE) suppressed intestinal BCRP expression and increased plasma concentrations of sulfasalazine in mice, accompanied by a reduction in certain bacterial populations. There was a correlation between BCRP expression and gut microbiota composition, suggesting modulation of gut microbiota may impact drug transporter-mediated interactions.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Review
Biochemistry & Molecular Biology
Ji He, Erika Fortunati, Dong-Xu Liu, Yan Li
Summary: Chemotherapeutics are a main therapy for metastatic breast cancers, but multidrug resistance due to ABC transporters remains a challenge. Targeting ABCB1 to reverse drug resistance in clinical trials has been disappointing, but ABC transporters may play roles in breast cancer development and metastasis beyond efflux function. Understanding the functions and regulations of ABC transporters in breast cancer biology may lead to more targeted and novel therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Pharmacology & Pharmacy
Jing-Quan Wang, Yuqi Yang, Chao-Yun Cai, Qiu-Xu Teng, Qingbin Cui, Jun Lin, Yehuda G. Assaraf, Zhe-Sheng Chen
Summary: ABC transporters mediate the translocation of structurally and mechanistically distinct substrates against steep concentration gradients using ATP energy. The ABCC subfamily is the largest in humans, with 13 members, including 9 multidrug resistance proteins that can extrude chemotherapeutic agents from tumor cells. Additionally, MRPs are also involved in the efflux of physiologically important organic anions and are potential targets for overcoming cancer multidrug resistance.
DRUG RESISTANCE UPDATES
(2021)
Article
Multidisciplinary Sciences
Harlan L. Pietz, Ata Abbas, Zachary Lee Johnson, Michael L. Oldham, Hiroaki Suga, Jue Chen
Summary: This study identifies a macrocyclic peptide CPI1 that inhibits the function of MRP1 and blocks substrate transport. The findings suggest that CPI1 could be a potential therapeutic candidate.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Chung-Pu Wu, Yen-Ching Li, Megumi Murakami, Sung-Han Hsiao, Yun-Chieh Lee, Yang-Hui Huang, Yu-Tzu Chang, Tai-Ho Hung, Yu-Shan Wu, Suresh V. Ambudkar
Summary: This study aims to evaluate whether furmonertinib overcomes drug resistance mediated by ABCB1 and ABCG2 transporters, and explore its interaction mechanisms with these proteins. The results suggest that furmonertinib holds potential as a candidate for combination therapy, enhancing the efficacy of conventional anticancer drugs and overcoming MDR in cancer treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Mohamed R. Abdelaal, Hesham Haffez
Summary: Multidrug resistance (MDR) refers to the phenomenon where tumor cells become unresponsive to one or more chemotherapeutic drugs during or after treatment. This critically limits treatment outcomes and poses a major challenge for clinicians. Alterations in intracellular drug concentration through the modulation of drug transport across the plasma membrane is the main cause of MDR, and this process involves various mediators, including ATP-requiring enzymes (ATPases). Among these ATPases, ABC transporters have been extensively studied and found to be highly implicated in tumorigenesis and MDR. This review focuses on the effects of retinoids on ABC enzymes and aims to understand their mechanism in combating cancer cell resistance.
Article
Oncology
Fariba Navid, Victor M. Santana, Michael Neel, M. Beth McCarville, Barry L. Shulkin, Jianrong Wu, Catherine A. Billups, Shenghua Mao, Vinay M. Daryani, Clinton F. Stewart, Michelle Kunkel, Wendene Smith, Deborah Ward, Alberto S. Pappo, Armita Bahrami, David M. Loeb, Jennifer Reikes Willert, Bhaskar N. Rao, Najat C. Daw
INTERNATIONAL JOURNAL OF CANCER
(2017)
Article
Oncology
Rachel C. Brennan, Ibrahim Qaddoumi, Shenghua Mao, Jianrong Wu, Catherine A. Billups, Clinton F. Stewart, Mary Ellen Hoehn, Carlos Rodriguez-Galindo, Matthew W. Wilson
JOURNAL OF CLINICAL ONCOLOGY
(2017)
Article
Pharmacology & Pharmacy
Ruby Leong, Hong Zhao, Gregory Reaman, Qi Liu, Yaning Wang, Clinton F. Stewart, Gilbert Burckart
JOURNAL OF CLINICAL PHARMACOLOGY
(2017)
Meeting Abstract
Surgery
Irada Ibrahim-Zada, Camille Stewart, Rodrigo Asturias Luna, Alyssa Blood, Csaba Gajdos, Barish Edil, Nathan Pearlman, Ana Gleisner, Martin D. McCarter
JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
(2017)
Article
Oncology
Anuradha Banerjee, Regina I. Jakacki, Arzu Onar-Thomas, Shengjie Wu, Theodore Nicolaides, Tina Young Poussaint, Jason Fangusaro, Joanna Phillips, Arie Perry, David Turner, Michael Prados, Roger J. Packer, Ibrahim Qaddoumi, Sridharan Gururangan, Ian F. Pollack, Stewart Goldman, Lawrence A. Doyle, Clinton F. Stewart, James M. Boyett, Larry E. Kun, Maryam Fouladi
Article
Oncology
Birgit V. Nimmervoll, Nidal Boulos, Brandon Bianski, Jason Dapper, Michael DeCuypere, Anang Shelat, Sabrina Terranova, Hope E. Terhune, Amar Gajjar, Yogesh T. Patel, Burgess B. Freeman, Arzu Onar-Thomas, Clinton F. Stewart, Martine F. Roussel, R. Kipling Guy, Thomas E. Merchant, Christopher Calabrese, Karen D. Wright, Richard J. Gilbertson
CLINICAL CANCER RESEARCH
(2018)
Article
Chemistry, Analytical
Bo Zhong, Anil Maharaj, Abigail Davis, Martine F. Roussel, Clinton F. Stewart
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2018)
Article
Oncology
Alberto Broniscer, Sujuan Jia, Belinda Mandrell, Dima Hamideh, Jie Huang, Arzu Onar-Thomas, Amar Gajjar, Susana C. Raimondi, Ruth G. Tatevossian, Clinton F. Stewart
PEDIATRIC BLOOD & CANCER
(2018)
Correction
Biochemistry & Molecular Biology
Jamie R. Genthe, Jaeki Min, Dana M. Farmer, Anang A. Shelat, Jose A. Grenet, Wenwei Lin, David Finkelstein, Karen Vrijens, Taosheng Chen, R. Kiplin Guy, Wilson K. Clements, Martine F. Roussel
ACS CHEMICAL BIOLOGY
(2019)
Article
Chemistry, Medicinal
Ho Shin Kim, Jared T. Hammill, Daniel C. Scott, Yizhe Chen, Jaeki Min, Jonah Rector, Bhuvanesh Singh, Brenda A. Schulman, R. Kiplin Guy
JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Article
Chemistry, Medicinal
Ho Shin Kim, Jared T. Hammill, Daniel C. Scott, Yizhe Chen, Amy L. Rice, William Pistel, Bhuvanesh Singh, Brenda A. Schulman, R. Kiplin Guy
Summary: This study has improved the pharmacokinetic performance of inhibitors targeting cullin-RING ubiquitin ligases and established the impact of the inhibitor on tumor cell growth.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Sreenath Nair, Abigail Davis, Olivia Campagne, John D. Schuetz, Clinton F. Stewart
Summary: This study successfully determined the concentration of IWR-1-endo in murine plasma and brain microdialysate using LC-MS/MS. pH adjustment to 1.5 improved the stability of IWR-1-endo in the samples before storage and processing.
Article
Biochemistry & Molecular Biology
Jamie R. Genthe, Jaeki Min, Dana M. Farmer, Anang A. Shelat, Jose A. Grenet, Wenwei Lin, David Finkelstein, Karen Vrijens, Taosheng Chen, R. Kiplin Guy, Wilson K. Clements, Martine F. Roussel
ACS CHEMICAL BIOLOGY
(2017)
Article
Oncology
Seth E. Karol, Wenjian Yang, Colton Smith, Cheng Cheng, Clinton F. Stewart, Sharyn D. Baker, John T. Sandlund, Jeffrey E. Rubnitz, Michael W. Bishop, Alberto S. Pappo, Sima Jeha, Ching-Hon Pui, Mary V. Relling
Meeting Abstract
Oncology
Abbas Shirinifard, Suresh Thiagarajan, Yogesh T. Patel, Abigail D. Davis, Megan O. Jacus, Jessica Roberts, Clinton F. Stewart, Andras Sablauer
Article
Pharmacology & Pharmacy
Paola Orlandi, Marta Banchi, Francesca Vaglini, Marco Carli, Stefano Aringhieri, Arianna Bandini, Carla Pardini, Cristina Viaggi, Michele Lai, Greta Ali, Alessandra Ottani, Eleonora Vandini, Patrizia Guidi, Margherita Bernardeschi, Veronica La Rocca, Giulio Francia, Gabriella Fontanini, Mauro Pistello, Giada Frenzilli, Daniela Giuliani, Marco Scarselli, Guido Bocci
Summary: This study investigates the role of MC4R in melanoma and the use of the selective antagonist ML in combination with vemurafenib. The results show that ML can inhibit melanoma cell proliferation and induce apoptosis through the inhibition of ERK1/2 phosphorylation and reduction of BCL-XL expression. The combination of vemurafenib and ML exhibits a synergistic effect in vitro and inhibits tumor growth in vivo without causing adverse effects.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Conor J. Bloxham, Katina D. Hulme, Fabrizio Fierro, Christian Fercher, Cassandra L. Pegg, Shannon L. O'Brien, Simon R. Foster, Kirsty R. Short, Sebastian G. B. Furness, Melissa E. Reichelt, Masha Y. Niv, Walter G. Thomas
Summary: Bitter taste receptors (T2Rs) are a type of G protein-coupled receptors that allow humans to detect aversive and toxic substances. This study characterized the functional properties of previously identified T2Rs in human cardiac tissues and their naturally occurring polymorphisms. The results showed differences in signaling among different T2R variants, and revealed a potential association between the T2R50 Tyr203 variant and cardiovascular disease.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Lu Chen, Huanying Shi, Wenxin Zhang, Yongjun Zhu, Haifei Chen, Zimei Wu, Huijie Qi, Jiafeng Liu, Mingkang Zhong, Xiaojin Shi, Tianxiao Wang, Qunyi Li
Summary: This study demonstrates that Carfilzomib exhibits potent anti-tumor activity against esophageal squamous cell carcinoma (ESCC) by triggering mitochondrial apoptosis and reprogramming cellular metabolism. It has been identified that activating transcription factor 3 (ATF3) plays a crucial role as a cellular target in ESCC cells treated with Carfilzomib. Overexpression of ATF3 effectively counteracts the effects of Carfilzomib on ESCC cell proliferation, apoptosis, and metabolic reprogramming. Furthermore, ATF3 mediates the anti-tumor activity of Carfilzomib, suggesting its potential as a therapeutic agent for ESCC.
BIOCHEMICAL PHARMACOLOGY
(2024)
Review
Pharmacology & Pharmacy
Xing Zhang, Xiang Li, Ran Xia, Hong-Sheng Zhang
Summary: This review summarizes recent progress on the mechanisms of ferroptosis resistance in cancer and highlights the role of redox status and metabolism. Combination therapy for ferroptosis has great potential in treating resistant malignant tumors.
BIOCHEMICAL PHARMACOLOGY
(2024)