Abstract:
:It is generally accepted that recent advances in anticancer agents have contributed significantly to the improvement of both the disease-free survival and quality of life in cancer patients. However, in many instances, a favorable initial response to treatment changes afterwards, thereby leading to cancer relapse and recurrence. This phenomenon of acquired resistance to therapy, it is a major problem for totally efficient anticancer therapy. The failure to obtain an initial response reflects a form of intrinsic resistance. Specific cell membrane transporter proteins are implicated in intrinsic drug resistance by altering drug transport and pumping drugs out of the tumor cells. Moreover, the gradual acquisition of specific genetic and epigenetic abnormalities in cancer cells could contribute greatly to acquired drug resistance. A critical issue in the clinical setting, is that the problem of drug resistance appears to have a negative effect on also the new molecularly-targeted anticancer drugs. Several ongoing efforts are being made by the medical community aimed to the identification of such resistance mechanisms and the development of novel drugs that could overcome them. In this review, the major drug resistance mechanisms and strategies to overcome them are critically discussed, and also possible future directions are suggested.
journal_name
Clin Exp Metastasisjournal_title
Clinical & experimental metastasisauthors
Nikolaou M,Pavlopoulou A,Georgakilas AG,Kyrodimos Edoi
10.1007/s10585-018-9903-0subject
Has Abstractpub_date
2018-04-01 00:00:00pages
309-318issue
4eissn
0262-0898issn
1573-7276pii
10.1007/s10585-018-9903-0journal_volume
35pub_type
杂志文章,评审abstract::The complex process of tumor invasion requires the coordinated expression and activity of cell-substratum adhesive interactions and of cell-associated protease systems, which destroy the extracellular matrix (ECM), in order to enable the invading cells to simultaneously grip and destroy the anatomical barriers that co...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章,评审
doi:10.1023/a:1015531321445
更新日期:2002-01-01 00:00:00
abstract::For more effective oncological management of disseminated colorectal cancer, therapies must be devised that target the different individual stages of metastasis development. Recent work showed that integrin subunits alpha2, alpha6 and beta4 are involved in the colorectal cancer cell extravasation process. By means of ...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-009-9276-5
更新日期:2009-01-01 00:00:00
abstract::Proliferation capacity and MHC class I antigen expression of two Lewis lung carcinoma (3LL) metastatic variants (C87, BC215) grown under defined experimental conditions (serum-free defined medium or 10 per cent serum) have been studied following exposure to MoAb 135-13C which recognizes on these cells a tumor surface ...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/BF02057180
更新日期:1989-01-01 00:00:00
abstract::Little is known about the biological characteristics that determine the prognosis of colorectal cancer (CRC) liver metastases. In previous work we reported three different histological patterns of the tumour-liver interface of CRC liver metastases, termed the pushing, replacement and desmoplastic growth pattern (GP). ...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-012-9469-1
更新日期:2012-08-01 00:00:00
abstract::Platelet-derived growth factor BB (PDGF BB) and the PDGF receptor beta are expressed on mesothelioma cells, but their biological function has not yet been defined. In the present study we used Boyden chambers fitted with filters coated with the adhesive matrix proteins fibronectin, laminin, collagen type IV or the non...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/a:1006542301794
更新日期:1998-08-01 00:00:00
abstract::Organ-specific metastasis of tumour cells may result from selective invasion and growth or from selective host cell responses. The present study demonstrates how selective interactions with the host affect the metastatic pattern of two murine T cell hybridoma lines, derived from the BW 5147 thymoma. Upon intravenous i...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/BF01753983
更新日期:1994-03-01 00:00:00
abstract::To evaluate the relationship between the c-kit proto-oncogene product and malignant transformation of human breast tissue, we examined the immunohistochemical expression of the c-kit proto-oncogene product in both malignant and non-malignant breast tissues. The immunohistochemical expression of the c-kit proto-oncogen...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/a:1027323210736
更新日期:2003-01-01 00:00:00
abstract::Hypermethylation of the promoter region of tumor suppressor genes is associated with carcinogenesis in lung cancer (LC). Endobronchial ultrasound with needle aspiration (EBUS-NA) is a semi-invasive method for obtaining cell blocks from lymph nodes, which can be used for epigenetic analyses. To establish the relationsh...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-015-9733-2
更新日期:2015-10-01 00:00:00
abstract::Human tissue factor pathway inhibitor-2 (TFPI-2), also known as placental protein (PP5) and matrix-associated serine protease inhibitor (MSPI), is a 32-kDa extracellular matrix (ECM) protein consisting of three tandomly arranged Kunitz-type domains that inhibits plasmin, trypsin, chymotrypsin, cathepsin G and plasma k...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/a:1011085820250
更新日期:2000-01-01 00:00:00
abstract::To evaluate the local control (LC), progression free survival (PFS), out-field PFS, overall survival (OS), toxicity and failure predictors of SRT in a series of various sites oligometastatic CRC patients. Patients with oligometastatic CRC disease were analyzed retrospectively. The SRT prescribed dose was dependent on ...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-019-09976-z
更新日期:2019-08-01 00:00:00
abstract::Previous studies from our laboratory have demonstrated that metastatic propensity is significantly influenced by the genetic background upon which tumors arise. We have also established that human gene expression profiles predictive of metastasis are not only present in mouse tumors with both high and low metastatic c...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-005-6244-6
更新日期:2005-01-01 00:00:00
abstract::The BRMS1 metastasis suppressor was recently shown to negatively regulate NF-kappaB signaling and down regulate NF-kappaB-dependent uPA expression. Here we confirm that BRMS1 expression correlates with reduced NF-kappaB DNA binding activity in independently derived human melanoma C8161.9 cells stably expressing BRMS1....
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-009-9235-1
更新日期:2009-01-01 00:00:00
abstract::Prostate cancer metastases form selectively in the bone marrow. Previously we demonstrated motility was important for the formation of primary prostatic epithelial cell colonies in bone marrow stroma (BMS) co-culture. In this study we looked at the influence of motility factors on the colony formation of epithelial ce...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/a:1006696002497
更新日期:1999-06-01 00:00:00
abstract::The mechanisms leading to rapid invasive growth of malignant gliomas are poorly understood. Expression of the hyaluronic acid (HA) receptor CD44 and adhesion to HA are involved in invasive properties. Our previous studies have shown that malignant glioma cells are able to adhere to extracellular HA. Here we investigat...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/a:1026425519497
更新日期:1999-02-01 00:00:00
abstract::The effects of the cyclooxygenase (COX)-2 inhibitor nimesulide on bombesin-enhanced peritoneal metastasis of azoxymethane (AOM)-induced intestinal adenocarcinomas were investigated in male Wistar rats. From the beginning of the study, the rats were given 10 weekly s.c. injections of AOM (7.4 mg/kg body weight) and s.c...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/a:1025883129932
更新日期:2003-01-01 00:00:00
abstract::Primary brain tumors lack the metastatic behavior that is in part believed to be promoted by the extracellular matrix (ECM) components of the basement membrane. This study was intended to examine the influence of the ECM components present in the basement membrane that may act as natural barriers to tumor cell invasio...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/BF00123395
更新日期:1996-09-01 00:00:00
abstract::MicroRNAs are a class of ≈22-nt noncoding single-strand RNAs regulating gene expression postscriptionally. Metastasis caused poor prognosis in colorectal cancer patients and half of the patients developed metastatic lesions when admission. Here we investigated the possible roles of microRNAs in regulating metastasis i...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-012-9463-7
更新日期:2012-06-01 00:00:00
abstract::Using alternative splicing reporters we have previously observed mesenchymal epithelial transitions in Dunning AT3 rat prostate tumors. We demonstrate here that the Dunning DT and AT3 cells, which express epithelial and mesenchymal markers, respectively, represent an excellent model to study epithelial transitions sin...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-008-9186-y
更新日期:2008-01-01 00:00:00
abstract::The expression of both 92- and 72-kDa gelatinases has been studied in 20 samples of human breast carcinoma by the technique of gelatin zymography. This technique allowed the relative amount of each gelatinase to be determined in small samples of tissue (< 10 mg). More importantly, active and latent forms of the two ge...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/BF00114976
更新日期:1993-03-01 00:00:00
abstract::A murine mammary carcinoma, which had a high potential for metastasis to the lungs, was established in culture, and from the parent line several clonally derived variants were isolated, showing different characteristics including metastatic potential. C1, a high metastatic clone, and C2, a low one, were selected for f...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/BF01784377
更新日期:1988-11-01 00:00:00
abstract::Brain metastases present a significant public health issue, affecting more than 100,000 patients per year in the U.S. and result in significant morbidity. Brain metastases can occur in a variety of clinical situations ranging from multiple brain metastases with uncontrolled systemic disease to a solitary metastasis in...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章,评审
doi:10.1007/s10585-017-9860-z
更新日期:2017-10-01 00:00:00
abstract::It is recognised that stromal cells determine cancer progression. We have previously shown that active TGFbeta produced by rat colon carcinoma cells modulated NO production in rat endothelial cells. To elucidate the role of TGFbeta and NO in the mechanisms of interaction of colon carcinoma cells with stromal cells and...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-005-0431-3
更新日期:2005-01-01 00:00:00
abstract::A previous study from our laboratory suggested that prostate cancer metastasis to bone may be mediated, in part, by preferential adhesion to human bone marrow endothelial (HBME) cells. Tumor cell adhesion to endothelial cells may be modulated by the effect of cytokines on cell adhesion molecules (CAMs). Tumor necrosis...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/a:1013849123736
更新日期:2002-01-01 00:00:00
abstract::Recent studies have indicated that KHT fibrosarcoma or B16 melanoma cell variants capable of forming experimental metastases in the lungs of mice after i.v. injection are created stochastically at high rates (approximately 10(-5)/cell/generation). Expression of this phenotype is unstable and hence expanding population...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/BF00117930
更新日期:1986-07-01 00:00:00
abstract::A number of papers have been published on the clinical correlation of the expression of the 67 kDa laminin binding protein (LBP) with the metastatic potential of solid tumors. Both mRNA and protein expression levels have been reported, but both the relationship between them and the molecular nature of the 67 kDa surfa...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/BF00121912
更新日期:1995-09-01 00:00:00
abstract::The function of tropomyosin receptor kinase (Trk) family including TrkA, TrkB, and TrkC in cancer remains unknown. The role of Trks in oral squamous cell carcinoma (OSCC) was examined. Knockdown of Trks provided inhibition of growth or invasion and decrease of apoptosis in OSCC cells, which expressed Trks at high leve...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-012-9525-x
更新日期:2013-02-01 00:00:00
abstract::Integrins expressed on endothelial cells modulate cell migration and survival during angiogenesis. Integrins expressed on carcinoma cells potentiate metastasis by facilitating invasion and movement across blood vessels. We describe the activities of two synthetic low-molecular-weight peptidomimetics of the ligand amin...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/b:clin.0000024764.93092.5f
更新日期:2004-01-01 00:00:00
abstract::We investigated the role of signal transduction systems in the attachment of human uveal melanoma cells to matrix proteins. Ocular melanoma cells established from primary tumours attached rapidly to all substrates examined. Preferred substrates of attachment were collagens type I, III and IV and fibronectin rather tha...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/BF01755881
更新日期:1994-11-01 00:00:00
abstract::Protein kinase C (PKC) has been shown to be a signal transducer during tumorigenesis, tumor cell invasion, and metastasis. Recent studies have reported that the PKC inhibitor, 7-hydroxystaurosporine, inhibits tumor cell invasion. However, the molecular mechanisms of this inhibition of invasion and metastasis are not w...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-007-9080-z
更新日期:2007-01-01 00:00:00
abstract::The glycosaminoglycans (GAGs) of low (LM) and highly metastatic (HM) cell lines of the Lewis lung tumour (3LL) were compared using [3H]glucosamine labelling techniques. The GAGs isolated from nuclei, cytoplasm, pericellular fractions and medium were analysed by cellulose acetate electrophoresis and by digestion with s...
journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/BF01753676
更新日期:1989-11-01 00:00:00