Abstract:
Background:Chemotherapy remains a major clinical option for the successful treatment of cancer by eliminating fast-growing populations of cancer cells. However, drug resistance causes the failure of antitumor treatment. Increasing evidence suggests that a small subpopulation of cancer cells will enter a "persister state" under drug pressure. The persister cell pool constitutes a reservoir from which drug resistance may emerge. Therefore, targeting persister cells presents a therapeutic opportunity to prevent drug resistance and impede tumor relapse. Materials and methods:RT-qPCR, Western blot, Seahorse, apoptosis assay, clonogenic assay, and xenografted mouse model were used for this study. Results:We showed that a similar therapy-resistant cell state underlies the behavior of persister cells derived from sorafenib treatments with reversible, nonmutational mechanisms. Then, we demonstrated that persister cells showed upregulated glycolysis, as evidenced by higher ECAR, as well as increased glucose consumption and lactate production. A database analysis showed that sorafenib-tolerant persister cells exhibited the increased expression of the glycolytic enzyme hexokinase 2, which is closely related to the poor prognosis in liver cancer. We found that the combined treatment with the glycolytic inhibitor 2-DG and sorafenib increased persister cell apoptosis and inhibited colony formation. Consequently, we demonstrated that when persister cells were exposed to a low concentration of sorafenib, they suffered mitochondrial dysfunction but showed compensatory increases in glycolysis, which contributes to cell growth and proliferation. Finally, we showed that the combination of 2-DG and sorafenib reduced persister tumor growth in mice. Conclusions:These findings suggest that such a combination can effectively hamper persister cell growth and may represent a promising therapeutic strategy to prevent persister cell resistance.
journal_name
Onco Targets Therjournal_title
OncoTargets and therapyauthors
Wang L,Yang Q,Peng S,Liu Xdoi
10.2147/OTT.S212465subject
Has Abstractpub_date
2019-07-08 00:00:00pages
5359-5373issn
1178-6930pii
212465journal_volume
12pub_type
杂志文章abstract:BACKGROUND:The purpose of this study was to evaluate clinical outcomes of conventional fractionated helical tomotherapy in patients with small to medium hepatocellular carcinomas (HCCs) without portal vein tumor thrombosis. METHODS:Patients with up to four HCC lesions not treatable by surgery or percutaneous ablative ...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S69618
更新日期:2014-09-26 00:00:00
abstract:Purpose:The aim was to investigate resveratrol effects on A549 cells proliferation. Methods:A total of 104 lung adenocarcinoma tissues and nontumor tissues were collected. BEAS-2B cells were cultured in RPMI 1640 medium (group A). A549 cells were treated with RPMI 1640 medium containing different resveratrol concentra...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S157613
更新日期:2018-05-22 00:00:00
abstract:BACKGROUND:Tumor cells before and after epidermal growth-factor receptor (EGFR) tyrosine-kinase inhibitor (TKI) therapy might display different characteristics. The aim of this study was to evaluate the influence of prior EGFR TKI therapy on the efficacy of subsequent pemetrexed plus platinum (PP) in advanced chemonaïv...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S62639
更新日期:2014-05-23 00:00:00
abstract::POEMS syndrome (acronym consisting of: polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) is an uncommon disorder associated with an underlying plasma cell dyscrasia. There is no single specific test for POEMS, and due to its rarity and heterogeneity, patients are often mis- or underdiagnosed. ...
journal_title:OncoTargets and therapy
pub_type:
doi:10.2147/OTT.S146221
更新日期:2018-09-27 00:00:00
abstract::Triple-negative breast cancer is associated with a poor prognosis, and effective biomarkers for targeted diagnosis and treatment are lacking. The tumorigenicity of the provirus integration site for Moloney murine leukemia virus 1 (PIM-1) gene has been studied for many years. However, its significance in breast cancer ...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S212752
更新日期:2019-08-08 00:00:00
abstract:Purpose:Tumor-associated macrophages (TAMs) originate from monocytes and differentiate into mature macrophages. The interaction between cancer cells and TAMs promotes tumor growth and suppresses immunosurveillance. However, this phenomenon has seldom been observed in ampullary cancer. Patients and Methods:TAMs in ampu...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S246714
更新日期:2020-08-03 00:00:00
abstract:AIM:To investigate the clinical significance of cyclic adenosine monophosphate-responsive element-binding (CREB) and phosphorylated CREB (pCREB) expression in human hepatocellular carcinoma (HCC). MATERIALS AND METHODS:Immunohistochemistry and Western blot analyses were performed to detect the expression and subcellul...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S63594
更新日期:2014-05-29 00:00:00
abstract::Normal astrocytes are more resistant to radiation than glioma cells. Radiation-resistant glioma cells and normal astrocytes usuallly share similar mechanisms of radioresistance. Investigation of the underlying mechanisms of differential radiation response between normal astrocytes and glioma cells is thus significant ...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S144002
更新日期:2017-12-04 00:00:00
abstract::The epidermal growth-factor receptor (EGFR) is overexpressed in the majority of epithelial ovarian cancers and promotes cell proliferation, migration and invasion, and angiogenesis, as well as resistance to apoptosis. This makes EGFR an attractive therapeutic target in this disease. A number of strategies to block EGF...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S30373
更新日期:2013-04-18 00:00:00
abstract:INTRODUCTION:The introduction of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has improved the outlook for patients with advanced non-small-cell lung cancer (NSCLC) with EGFR+ mutations. However, most patients develop resistance, with the result that median progression-free survival (PFS) iŝ1...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S134382
更新日期:2017-05-05 00:00:00
abstract::The mortality of hepatobiliary cancer still stays high around the world, with disappointing treatment status at advanced stage. Genomic analysis has identified the global spectrum of alterations in liver cancer, but the most common mutations are not actionable, meanwhile lacking potent molecular-targeted drugs for spe...
journal_title:OncoTargets and therapy
pub_type:
doi:10.2147/OTT.S223568
更新日期:2019-11-19 00:00:00
abstract::Gastric cancer (GC) is one of the leading causes of tumor-related mortality. In addition to surgery and endoscopic resection, systemic therapy remains the main treatment option for GC, especially for advanced-stage disease and for cases not suitable for surgical therapy. Hence, improving the efficacy of systemic thera...
journal_title:OncoTargets and therapy
pub_type: 杂志文章,评审
doi:10.2147/OTT.S221354
更新日期:2019-12-24 00:00:00
abstract::The use of additional radiotherapy for resected stage IIIA N2 non-small-cell lung cancer in the setting of standard adjuvant chemotherapy remains controversial. A comprehensive search (last search updated in March 2015) for relevant studies comparing patients with stage IIIA N2 non-small-cell lung cancer undergoing re...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S95517
更新日期:2016-02-24 00:00:00
abstract:Purpose:Although cisplatin-based adjuvant chemotherapy improves the survival of patients with resected non-small-cell lung cancer, not all patients show a survival benefit, and some patients experience severe toxicity. Therefore, identifying biomarkers is important for selecting subgroups of patients who may show impro...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S145072
更新日期:2017-11-02 00:00:00
abstract:BACKGROUND:Everolimus, an inhibitor of the mammalian target of rapamycin, shows promising antitumor activity when combined with trastuzumab and chemotherapy for human epidermal growth factor receptor-2 (HER2)-positive breast cancer or when combined with endocrine agents for hormone receptor (HR)-positive tumors. Howeve...
journal_title:OncoTargets and therapy
pub_type:
doi:10.2147/OTT.S104398
更新日期:2016-07-01 00:00:00
abstract::Tamoxifen was the first targeted anticancer agent for breast cancer patients and its effects on reduction of breast cancer events and improvement in overall survival are undisputed. Hence, it has long been considered an essential part of patient care. Recent results of several large adjuvant hormonal trials evaluating...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S10155
更新日期:2010-12-17 00:00:00
abstract::The aim of this study was to evaluate the efficacy and toxicity of stereotactic body radiation therapy (SBRT) in the treatment of patients with liver metastases. Between August 2006 and July 2011, patients with 1-4 liver metastases were enrolled and treated with SBRT using the CyberKnife(®) system at Tianjin Medical U...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S58409
更新日期:2014-06-12 00:00:00
abstract:OBJECTIVE:To study microRNA (miR)-20a expression in hepatocellular carcinoma (HCC) and its effects on the proliferation, migration, and invasion of HepG2. METHODS:The real-time polymerase chain reaction was used to detect the expression of miR-20a in HCC tissue and normal tissue, as well as in HCC cell lines and norma...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S96861
更新日期:2016-05-27 00:00:00
abstract::Acute myeloid leukemia (AML) is an aggressive hematopoietic malignancy that is cured in as few as 15%-40% of cases. Tremendous improvements in AML prognostication arose from a comprehensive analysis of leukemia cell genomes. Among normal karyotype AML cases, mutations in the FLT3 gene are the ones most commonly detect...
journal_title:OncoTargets and therapy
pub_type: 杂志文章,评审
doi:10.2147/OTT.S103790
更新日期:2017-02-03 00:00:00
abstract:Introduction:Odd-skipped related transcription factor 1 (OSR1) is a newly identified tumor suppressor in many tumor types. However, the role and mechanism of OSR1 in colon adenocarcinoma (COAD) remain unknown. Methods:OSR1 expression was detected in COAD tissues and cells. COAD cells with OSR1 overexpression or knockd...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S242386
更新日期:2020-04-24 00:00:00
abstract::Advances in therapies have led to the approval of six therapeutic agents since 2004, each demonstrating overall survival benefit in randomized studies, and these have significantly improved the outlook for men facing metastatic castration-resistant prostate cancer (CRPC). More recently, efforts have been directed at t...
journal_title:OncoTargets and therapy
pub_type: 杂志文章,评审
doi:10.2147/OTT.S147168
更新日期:2018-04-12 00:00:00
abstract::The study aimed to investigate the difference of setup errors on different registration in the treatment of nasopharyngeal carcinoma based on weekly cone-beam computed tomography (CBCT). Thirty nasopharyngeal cancer patients scheduled to undergo intensity-modulated radiotherapy (IMRT) were prospectively enrolled in th...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S87159
更新日期:2015-09-14 00:00:00
abstract:AIM:The aim of this study was to assess if the expression of Notch 1 receptor is associated with tumor aggressiveness in papillary thyroid carcinomas (PTCs). PATIENTS AND METHODS:By searching the electronic medical record system of Xin Hua Hospital, all cases of PTC patients who underwent thyroidectomy in the hospital...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S98239
更新日期:2016-03-15 00:00:00
abstract:Purpose:Cutaneous squamous cell carcinoma (cSCC) is the second most common form of skin cancer and its incidence continues to rise yearly. Photodynamic therapy (PDT) is a non-invasive form of cancer therapy, which utilizes the combined action of a photosensitizer, light, and oxygen molecules to selectively cause cellul...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S228792
更新日期:2019-12-31 00:00:00
abstract::Multiple drug resistance is still an unsolved problem in cancer therapy. Our previous study demonstrated that the chemotherapeutic drug doxorubicin (Dox) induced upregulation of P-glycoprotein (P-gp) in endothelial cells, resulting in a 20-fold increase in drug resistance and reduced efficiency of Dox treatment in a m...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S67251
更新日期:2014-12-04 00:00:00
abstract::Liposarcoma (LPS) is the most common type of soft-tissue sarcoma. Complete surgical resection is the only curative means for localized disease; however, both radiation and conventional cytotoxic chemotherapy remain controversial for metastatic or unresectable disease. An increasing number of trials with novel targeted...
journal_title:OncoTargets and therapy
pub_type: 杂志文章,评审
doi:10.2147/OTT.S72722
更新日期:2015-01-05 00:00:00
abstract:Background:Gastric cancer (GC) is an aggressive malignancy with high lethality. Systematic chemotherapy is the main therapeutic strategy for advanced GC patients. The overexpression of Axl is associated with poor prognosis and regulates tumor growth and metastasis in many types of cancer. However, the role of Axl in GC...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S257606
更新日期:2020-06-22 00:00:00
abstract:Background:Since colorectal cancer (CRC) is one of the most common malignant tumors worldwide, we aimed to identify the role of sex determining region Y (SRY)-box 18 (SOX18) in CRC. Methods:RT-PCR and immunohistochemistry were employed to detect the expression of SOX18 in CRC samples. We then identified the effect of ...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S178916
更新日期:2018-11-29 00:00:00
abstract:Objective:Cumulative data from clinical trials suggest that Lin28 may contribute to poor survival in breast cancer patients. The purpose of this study was to investigate the relationship between Lin28 expression and breast cancer patients' clinicopathological parameters. Methods:Data from a total of 291 breast cancer ...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S190328
更新日期:2019-02-08 00:00:00
abstract:Purpose:As a novel type of non-coding RNAs, circRNAs were found to play important roles in cancer progression. In this study, we aim to investigate genome-wide circRNAs expression and potential functions in glioma to find new therapeutic targets for glioma treatment. Patients and Methods:A total of 92 pairs of glioma ...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S241347
更新日期:2020-04-01 00:00:00