Repurposing Tyrosine Kinase Inhibitors to Overcome Multidrug Resistance in Cancer: A Focus on Transporters and Lysosomal Sequestration

Assessment of Treatment With Sorafenib Plus Doxorubicin vs Sorafenib Alone in Patients With Advanced Hepatocellular Carcinoma

(2019) Ghassan K. Abou-Alfa et al.   JAMA Oncology

Gefitinib Alone Versus Gefitinib Plus Chemotherapy for Non–Small-Cell Lung Cancer With Mutated Epidermal Growth Factor Receptor: NEJ009 Study

(2019) Yukio Hosomi et al.   JOURNAL OF CLINICAL ONCOLOGY

Sorafenib in combination with gemcitabine plus cisplatin chemotherapy in metastatic renal collecting duct carcinoma: A prospective, multicentre, single-arm, phase 2 study

(2018) Xinan Sheng et al.   EUROPEAN JOURNAL OF CANCER

Tumor stressors induce two mechanisms of intracellular P-glycoprotein–mediated resistance that are overcome by lysosomal-targeted thiosemicarbazones

(2018) Lina Al-Akra et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

ABCC6 plays a significant role in the transport of nilotinib and dasatinib, and contributes to TKI resistance in vitro, in both cell lines and primary patient mononuclear cells

(2018) Laura N. Eadie et al.   PLoS One

Role of drug transporters in the sensitivity of acute myeloid leukemia to sorafenib

(2018) Rocio I.R. Macias et al.   Oncotarget

Apatinib combined with oral etoposide in patients with platinum-resistant or platinum-refractory ovarian cancer (AEROC): a phase 2, single-arm, prospective study

(2018) Chun-Yan Lan et al.   LANCET ONCOLOGY

P-glycoprotein and Breast Cancer Resistance Protein restrict brigatinib brain accumulation and toxicity, and, alongside CYP3A, limit its oral availability

(2018) Wenlong Li et al.   PHARMACOLOGICAL RESEARCH

ATP-binding cassette transporters in progression and clinical outcome of pancreatic cancer: What is the way forward?

(2018) Aleksandra Adamska et al.   WORLD JOURNAL OF GASTROENTEROLOGY

ABCC10 Plays a Significant Role in the Transport of Gefitinib and Contributes to Acquired Resistance to Gefitinib in NSCLC

(2018) Hongbo Zhao et al.   Frontiers in Pharmacology

Role of uL3 in Multidrug Resistance in p53-Mutated Lung Cancer Cells

(2017) Annapina Russo et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Sequential delivery of erlotinib and doxorubicin for enhanced triple negative Breast cancer treatment using polymeric nanoparticle

(2017) Zilan Zhou et al.   INTERNATIONAL JOURNAL OF PHARMACEUTICS

Afatinib Decreases P-Glycoprotein Expression to Promote Adriamycin Toxicity of A549T Cells

(2017) Yan Zhang et al.   JOURNAL OF CELLULAR BIOCHEMISTRY

Intrinsic fluorescence of the clinically approved multikinase inhibitor nintedanib reveals lysosomal sequestration as resistance mechanism in FGFR-driven lung cancer

(2017) Bernhard Englinger et al.   JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH

Inhibitory Effect of Crizotinib on Creatinine Uptake by Renal Secretory Transporter OCT2

(2017) Hiroshi Arakawa et al.   JOURNAL OF PHARMACEUTICAL SCIENCES

A pilot clinical study of apatinib plus irinotecan in patients with recurrent high-grade glioma

(2017) Lei Wang et al.   MEDICINE

The BTK Inhibitor Ibrutinib (PCI-32765) Overcomes Paclitaxel Resistance in ABCB1- and ABCC10-Overexpressing Cells and Tumors

(2017) Hui Zhang et al.   MOLECULAR CANCER THERAPEUTICS

Breast cancer resistance protein (BCRP/ABCG2) and P-glycoprotein (P-gp/ABCB1) transport afatinib and restrict its oral availability and brain accumulation

(2017) Stéphanie van Hoppe et al.   PHARMACOLOGICAL RESEARCH

Modulating the function of ATP-binding cassette subfamily G member 2 (ABCG2) with inhibitor cabozantinib

(2017) Guan-Nan Zhang et al.   PHARMACOLOGICAL RESEARCH

Quizartinib (AC220) reverses ABCG2-mediated multidrug resistance: In vitro and in vivo studies

(2017) Jun Li et al.   Oncotarget

Lapatinib potentiates cytotoxicity of  YM155 in neuroblastoma via inhibition of the ABCB1 efflux transporter

(2017) Branka Radic-Sarikas et al.   Scientific Reports

“Combo” nanomedicine: Co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy

(2016) Jessica A. Kemp et al.   ADVANCED DRUG DELIVERY REVIEWS

TKI combination therapy: strategy to enhance dasatinib uptake by inhibiting Pgp- and BCRP-mediated efflux

(2016) Ronilda D'Cunha et al.   BIOPHARMACEUTICS & DRUG DISPOSITION

Pharmacokinetic drug-drug interactions of tyrosine kinase inhibitors: A focus on cytochrome P450, transporters, and acid suppression therapy

(2016) Caroline Gay et al.   HEMATOLOGICAL ONCOLOGY

Erlotinib, cabozantinib, or erlotinib plus cabozantinib as second-line or third-line treatment of patients with EGFR wild-type advanced non-small-cell lung cancer (ECOG-ACRIN 1512): a randomised, controlled, open-label, multicentre, phase 2 trial

(2016) Joel W Neal et al.   LANCET ONCOLOGY

Osimertinib (AZD9291) Enhanced the Efficacy of Chemotherapeutic Agents in ABCB1- and ABCG2-Overexpressing Cells In Vitro, In Vivo, and Ex Vivo

(2016) Z. Chen et al.   MOLECULAR CANCER THERAPEUTICS

MRP3 as a novel resistance factor for sorafenib in hepatocellular carcinoma

(2016) Tetsu Tomonari et al.   Oncotarget

Acquired nintedanib resistance in FGFR1-driven small cell lung cancer: role of endothelin-A receptor-activated ABCB1 expression

(2016) Bernhard Englinger et al.   Oncotarget

Phase II trial of everolimus and erlotinib in patients with platinum-resistant recurrent and/or metastatic head and neck squamous cell carcinoma

(2015) E. Massarelli et al.   ANNALS OF ONCOLOGY

The effect of BMS-582949, a P38 mitogen-activated protein kinase (P38 MAPK) inhibitor on arterial inflammation: A multicenter FDG-PET trial

(2015) Hamed Emami et al.   ATHEROSCLEROSIS

Identification of new MRP4 inhibitors from a library of FDA approved drugs using a high-throughput bioluminescence screen

(2015) Leanna Cheung et al.   BIOCHEMICAL PHARMACOLOGY

Vatalanib sensitizes ABCB1 and ABCG2-overexpressing multidrug resistant colon cancer cells to chemotherapy under hypoxia

(2015) Kenneth K.W. To et al.   BIOCHEMICAL PHARMACOLOGY

Nilotinib combined with multiagent chemotherapy for newly diagnosed Philadelphia-positive acute lymphoblastic leukemia

(2015) D.-Y. Kim et al.   BLOOD

Multikinase Inhibitors Induce Cutaneous Toxicity through OAT6-Mediated Uptake and MAP3K7-Driven Cell Death

(2015) E. I. Zimmerman et al.   CANCER RESEARCH

Di-2-pyridylketone 4,4-Dimethyl-3-thiosemicarbazone (Dp44mT) Overcomes Multidrug Resistance by a Novel Mechanism Involving the Hijacking of Lysosomal P-Glycoprotein (Pgp)

(2015) Patric J. Jansson et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Cediranib or placebo in combination with cisplatin and gemcitabine chemotherapy for patients with advanced biliary tract cancer (ABC-03): a randomised phase 2 trial

(2015) Juan W Valle et al.   LANCET ONCOLOGY

Cediranib combined with carboplatin and paclitaxel in patients with metastatic or recurrent cervical cancer (CIRCCa): a randomised, double-blind, placebo-controlled phase 2 trial

(2015) R Paul Symonds et al.   LANCET ONCOLOGY

SLC transporters as therapeutic targets: emerging opportunities

(2015) Lawrence Lin et al.   NATURE REVIEWS DRUG DISCOVERY

Binding-induced, turn-on fluorescence of the EGFR/ERBB kinase inhibitor, lapatinib

(2015) James N. Wilson et al.   ORGANIC & BIOMOLECULAR CHEMISTRY

Photoactivation of lysosomally sequestered sunitinib after angiostatic treatment causes vascular occlusion and enhances tumor growth inhibition

(2015) P Nowak-Sliwinska et al.   Cell Death & Disease

Cross-resistance to clinically used tyrosine kinase inhibitors sunitinib, sorafenib and pazopanib

(2015) Kristy J. Gotink et al.   CELLULAR ONCOLOGY

Effect of ceritinib (LDK378) on enhancement of chemotherapeutic agents in ABCB1 and ABCG2 overexpressing cells in vitro and in vivo

(2015) Jing Hu et al.   Oncotarget

Icotinib antagonizes ABCG2-mediated multidrug resistance, but not the pemetrexed resistance mediated by thymidylate synthase and ABCG2

(2015) De-Shen Wang et al.   Oncotarget

Combined MTOR and autophagy inhibition

(2014) Reshma Rangwala et al.   Autophagy

A phase I/II trial of hydroxychloroquine in conjunction with radiation therapy and concurrent and adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme

(2014) Myrna R Rosenfeld et al.   Autophagy

Motesanib (AMG706), a potent multikinase inhibitor, antagonizes multidrug resistance by inhibiting the efflux activity of the ABCB1

(2014) Yi-Jun Wang et al.   BIOCHEMICAL PHARMACOLOGY

Telatinib reverses chemotherapeutic multidrug resistance mediated by ABCG2 efflux transporter in vitro and in vivo

(2014) Kamlesh Sodani et al.   BIOCHEMICAL PHARMACOLOGY

Inhibition of OATP1B1 by tyrosine kinase inhibitors: in vitro–in vivo correlations

(2014) S Hu et al.   BRITISH JOURNAL OF CANCER

In vitro,in vivoandex vivocharacterization of ibrutinib: a potent inhibitor of the efflux function of the transporter MRP1

(2014) Hui Zhang et al.   BRITISH JOURNAL OF PHARMACOLOGY

Phase I dosage finding and pharmacokinetic study of intravenous topotecan and oral erlotinib in adults with refractory solid tumors

(2014) Clinton F. Stewart et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

Linsitinib (OSI-906) antagonizes ATP-binding cassette subfamily G member 2 and subfamily C member 10-mediated drug resistance

(2014) Hui Zhang et al.   INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY

Masitinib antagonizes ATP-binding cassette subfamily G member 2-mediated multidrug resistance

(2014) RISHIL J. KATHAWALA et al.   INTERNATIONAL JOURNAL OF ONCOLOGY

Safety and Efficacy of Neratinib in Combination With Capecitabine in Patients With Metastatic Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer

(2014) Cristina Saura et al.   JOURNAL OF CLINICAL ONCOLOGY

Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised controlled trial

(2014) Martin Reck et al.   LANCET ONCOLOGY

Cabozantinib reverses multidrug resistance of human hepatoma HepG2/adr cells by modulating the function of P-glycoprotein

(2014) Qing-feng Xiang et al.   LIVER INTERNATIONAL

Masitinib Antagonizes ATP-Binding Cassette Subfamily C Member 10-Mediated Paclitaxel Resistance: A Preclinical Study

(2014) R. J. Kathawala et al.   MOLECULAR CANCER THERAPEUTICS

Imaging the intracellular distribution of tyrosine kinase inhibitors in living cells with quantitative hyperspectral stimulated Raman scattering

(2014) Dan Fu et al.   Nature Chemistry

Ponatinib enhances anticancer drug sensitivity in MRP7-overexpressing cells

(2014) YUE-LI SUN et al.   ONCOLOGY REPORTS

Correction: Imatinib and Nilotinib Reverse Multidrug Resistance in Cancer Cells by Inhibiting the Efflux Activity of the MRP7 (ABCC10)

(2014) Tong Shen et al.   PLoS One

Giant Lysosomes as a Chemotherapy Resistance Mechanism in Hepatocellular Carcinoma Cells

(2014) Federico Colombo et al.   PLoS One

Combination neratinib (HKI-272) and paclitaxel therapy in patients with HER2-positive metastatic breast cancer

(2013) L W-C Chow et al.   BRITISH JOURNAL OF CANCER

Tyrosinekinase inhibition facilitates cooperation of transcription factor SALL4 and ABC transporter A3 towards intrinsic CML cell drug resistance

(2013) Timo Hupfeld et al.   BRITISH JOURNAL OF HAEMATOLOGY

Increased oral availability and brain accumulation of the ALK inhibitor crizotinib by coadministration of the P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) inhibitor elacridar

(2013) Seng Chuan Tang et al.   INTERNATIONAL JOURNAL OF CANCER

P-glycoprotein Mediates Drug Resistance via a Novel Mechanism Involving Lysosomal Sequestration

(2013) Tetsuo Yamagishi et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Lapatinib plus capecitabine for HER2-positive advanced breast cancer: a multicentre study of Anatolian Society of Medical Oncology (ASMO)

(2013) Bulent Cetin et al.   JOURNAL OF CHEMOTHERAPY

Sorafenib in Combination With Intensive Chemotherapy in Elderly Patients With Acute Myeloid Leukemia: Results From a Randomized, Placebo-Controlled Trial

(2013) Hubert Serve et al.   JOURNAL OF CLINICAL ONCOLOGY

Phase III Trial of Sunitinib in Combination With Capecitabine Versus Capecitabine Monotherapy for the Treatment of Patients With Pretreated Metastatic Breast Cancer

(2013) John P. Crown et al.   JOURNAL OF CLINICAL ONCOLOGY

Sunitinib and SU11652 Inhibit Acid Sphingomyelinase, Destabilize Lysosomes, and Inhibit Multidrug Resistance

(2013) A.-M. Ellegaard et al.   MOLECULAR CANCER THERAPEUTICS

Gemcitabine Plus Erlotinib for Advanced Pancreatic Cancer: A Systematic Review with Meta-Analysis

(2013) Zu-Yao Yang et al.   PLoS One

Randomised phase II trial of docetaxel and sunitinib in patients with metastatic gastric cancer who were previously treated with fluoropyrimidine and platinum

(2012) J H Yi et al.   BRITISH JOURNAL OF CANCER

Nilotinib potentiates anticancer drug sensitivity in murine ABCB1-, ABCG2-, and ABCC10-multidrug resistance xenograft models

(2012) Amit K. Tiwari et al.   CANCER LETTERS

Saracatinib (AZD0530) is a potent modulator of ABCB1-mediated multidrug resistancein vitroandin vivo

(2012) Ke-Jun Liu et al.   INTERNATIONAL JOURNAL OF CANCER

Enhanced brain accumulation of pazopanib by modulating P-gp and Bcrp1 mediated efflux with canertinib or erlotinib

(2012) Mukul Minocha et al.   INTERNATIONAL JOURNAL OF PHARMACEUTICS

First-Line Treatment of Advanced Breast Cancer With Sunitinib in Combination With Docetaxel Versus Docetaxel Alone: Results of a Prospective, Randomized Phase III Study

(2012) Jonas Bergh et al.   JOURNAL OF CLINICAL ONCOLOGY

ALK inhibitor crizotinib combined with intrathecal methotrexate treatment for non-small cell lung cancer with leptomeningeal carcinomatosis

(2012) Hee Kyung Ahn et al.   LUNG CANCER

The Novel BCR-ABL and FLT3 Inhibitor Ponatinib Is a Potent Inhibitor of the MDR-Associated ATP-Binding Cassette Transporter ABCG2

(2012) R. Sen et al.   MOLECULAR CANCER THERAPEUTICS

Autophagy inhibitor Lys05 has single-agent antitumor activity and reproduces the phenotype of a genetic autophagy deficiency

(2012) Q. McAfee et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Multidrug Resistance Protein 2 Implicates Anticancer Drug-Resistance to Sorafenib

(2011) Yoshihiko Shibayama et al.   BIOLOGICAL & PHARMACEUTICAL BULLETIN

Lysosomal Sequestration of Sunitinib: A Novel Mechanism of Drug Resistance

(2011) K. J. Gotink et al.   CLINICAL CANCER RESEARCH

Nuclear Translocation of Epidermal Growth Factor Receptor by Akt-dependent Phosphorylation Enhances Breast Cancer-resistant Protein Expression in Gefitinib-resistant Cells

(2011) Wei-Chien Huang et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Vandetanib Plus Pemetrexed for the Second-Line Treatment of Advanced Non–Small-Cell Lung Cancer: A Randomized, Double-Blind Phase III Trial

(2011) Richard H. de Boer et al.   JOURNAL OF CLINICAL ONCOLOGY

Double-Blind, Randomized Trial of Docetaxel Plus Vandetanib Versus Docetaxel Plus Placebo in Platinum-Pretreated Metastatic Urothelial Cancer

(2011) Toni K. Choueiri et al.   JOURNAL OF CLINICAL ONCOLOGY

Interactions of Tyrosine Kinase Inhibitors with Organic Cation Transporters and Multidrug and Toxic Compound Extrusion Proteins

(2011) T. Minematsu et al.   MOLECULAR CANCER THERAPEUTICS

The Emergence of Drug Transporter-Mediated Multidrug Resistance to Cancer Chemotherapy

(2011) Chung-Pu Wu et al.   MOLECULAR PHARMACEUTICS

Elevated BCRP/ABCG2 Expression Confers Acquired Resistance to Gefitinib in Wild-Type EGFR-Expressing Cells

(2011) Yun-Ju Chen et al.   PLoS One

Sunitinib rechallenge in metastatic renal cell carcinoma patients

(2010) Ivan N. Zama et al.   CANCER

Apatinib (YN968D1) Reverses Multidrug Resistance by Inhibiting the Efflux Function of Multiple ATP-Binding Cassette Transporters

(2010) Y.-j. Mi et al.   CANCER RESEARCH

Src Family Kinase Inhibitor Saracatinib (AZD0530) Impairs Oxaliplatin Uptake in Colorectal Cancer Cells and Blocks Organic Cation Transporters

(2010) C. J. Morrow et al.   CANCER RESEARCH

Role of ATP-Binding Cassette and Solute Carrier Transporters in Erlotinib CNS Penetration and Intracellular Accumulation

(2010) M. A. Elmeliegy et al.   CLINICAL CANCER RESEARCH

A phase II study of erlotinib (OSI-774) given in combination with carboplatin in patients with recurrent epithelial ovarian cancer (NCIC CTG IND.149)

(2010) H. Hirte et al.   GYNECOLOGIC ONCOLOGY

Functional Activity of the OCT-1 Protein Is Predictive of Long-Term Outcome in Patients With Chronic-Phase Chronic Myeloid Leukemia Treated With Imatinib

(2010) Deborah L. White et al.   JOURNAL OF CLINICAL ONCOLOGY

Chronic Myeloid Leukemia CD34+ cells have reduced uptake of imatinib due to low OCT-1 Activity

(2010) J R Engler et al.   LEUKEMIA

An Oral Spleen Tyrosine Kinase (Syk) Inhibitor for Rheumatoid Arthritis

(2010) Michael E. Weinblatt et al.   NEW ENGLAND JOURNAL OF MEDICINE

A high content screening assay for identifying lysosomotropic compounds

(2010) Sashi Nadanaciva et al.   TOXICOLOGY IN VITRO

Regulation of P-glycoprotein and other ABC drug transporters at the blood–brain barrier

(2010) David S. Miller   TRENDS IN PHARMACOLOGICAL SCIENCES

Lapatinib and erlotinib are potent reversal agents for MRP7 (ABCC10)-mediated multidrug resistance

(2009) Ye-Hong Kuang et al.   BIOCHEMICAL PHARMACOLOGY

Increased levels and defective glycosylation of MRPs in ovarian carcinoma cells resistant to oxaliplatin

(2009) Giovanni Luca Beretta et al.   BIOCHEMICAL PHARMACOLOGY

Interaction of nilotinib, dasatinib and bosutinib with ABCB1 and ABCG2: implications for altered anti-cancer effects and pharmacological properties

(2009) C Hegedűs et al.   BRITISH JOURNAL OF PHARMACOLOGY

Cediranib (recentin, AZD2171) reverses ABCB1- and ABCC1-mediated multidrug resistance by inhibition of their transport function

(2009) Li-yang Tao et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

Interaction of the Multikinase Inhibitors Sorafenib and Sunitinib with Solute Carriers and ATP-Binding Cassette Transporters

(2009) S. Hu et al.   CLINICAL CANCER RESEARCH

ABC transporter A3 facilitates lysosomal sequestration of imatinib and modulates susceptibility of chronic myeloid leukemia cell lines to this drug

(2009) B. Chapuy et al.   HAEMATOLOGICA

Nilotinib-mediated inhibition of ABCB1 increases intracellular concentration of dasatinib in CML cells: implications for combination TKI therapy

(2009) D K Hiwase et al.   LEUKEMIA

Nilotinib concentration in cell lines and primary CD34+ chronic myeloid leukemia cells is not mediated by active uptake or efflux by major drug transporters

(2009) A Davies et al.   LEUKEMIA

Vandetanib (Zactima, ZD6474) Antagonizes ABCC1- and ABCG2-Mediated Multidrug Resistance by Inhibition of Their Transport Function

(2009) Li-sheng Zheng et al.   PLoS One

Lapatinib (Tykerb, GW572016) Reverses Multidrug Resistance in Cancer Cells by Inhibiting the Activity of ATP-Binding Cassette Subfamily B Member 1 and G Member 2

(2008) C.-l. Dai et al.   CANCER RESEARCH

Interaction of Imatinib with Human Organic Ion Carriers

(2008) S. Hu et al.   CLINICAL CANCER RESEARCH

Sunitinib (Sutent, SU11248), a Small-Molecule Receptor Tyrosine Kinase Inhibitor, Blocks Function of the ATP-Binding Cassette (ABC) Transporters P-Glycoprotein (ABCB1) and ABCG2

(2008) S. Shukla et al.   DRUG METABOLISM AND DISPOSITION

Phase III, Double-Blind, Randomized Study Comparing Lapatinib Plus Paclitaxel With Placebo Plus Paclitaxel As First-Line Treatment for Metastatic Breast Cancer

(2008) Angelo Di Leo et al.   JOURNAL OF CLINICAL ONCOLOGY

Tyrosine kinase inhibitors reverse type 1 diabetes in nonobese diabetic mice

(2008) C. Louvet et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA