Cancer Drug Resistance

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (30 June 2014) | Viewed by 89685

Special Issue Editor

Department of Biopharmaceutical Sciences, College of Pharmacy and Cancer Center, University of Illinois at Chicago, Chicago, IL 60612, USA
Interests: multidrug resistance; ABC transporters; tumorigenesis; targeted therapy; alternative splicing; cancer stem cells; gene targeting; biomarkers

Special Issue Information

Dear Colleagues,

Drug resistance represents a major obstacle to the success of cancer treatments. Drug resistance occurs not only with classical chemotherapeutics, but also with more recent, molecularly-targeted therapies. A variety of molecular mechanisms have been implicated in the development of resistance; these mechanisms include increased drug efflux, altered drug metabolism, mutated or amplified drug targets, enhanced compensatory signaling pathways, etc.

Modern technologies in genomics, proteomics, and epigenomics have made it possible to dissect the molecular changes underlying drug resistance in an unprecedentedly detailed and comprehensive manner. The current challenge is to identify clinically meaningful biomarkers from these “-omics” studies so as to predict individual patients' responses to particular drugs and devise drug combinations to overcome or prevent potential resistance. This Special Issue is devoted to publishing original research reports and review articles that concern drug resistance in cancer treatment. The topics can be, but are not limited to the following:

  • High-throughput analysis of drug-sensitive and resistant human tumors
  • Epigenetic changes in drug-resistant cancer cells
  • microRNAs in the development of cancer drug resistance
  • Biomarkers for prediction of drug response
  • ABC transporters in drug resistance
  • Tumor heterogeneity and drug resistance
  • Treatment of resistant cancer cells

Dr. Xiaolong He
Guest Editor

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cancer drug resistance
  • chemotherapy
  • targeted therapy
  • biomarkers
  • microarray
  • microRNA
  • ABC transporters
  • high-throughput analysis

Published Papers (5 papers)

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Research

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546 KiB  
Article
Gefitinib Plus Interleukin-2 in Advanced Non-Small Cell Lung Cancer Patients Previously Treated with Chemotherapy
by Melissa Bersanelli, Sebastiano Buti, Roberta Camisa, Matteo Brighenti, Silvia Lazzarelli, Giancarlo Mazza and Rodolfo Passalacqua
Cancers 2014, 6(4), 2035-2048; https://doi.org/10.3390/cancers6042035 - 30 Sep 2014
Cited by 11 | Viewed by 6910
Abstract
The activation of lymphocytes by gefitinib treatment has been described. In this phase II pilot trial, we explored the possible synergism between IL-2 and gefitinib for non-small cell lung cancer (NSCLC) treatment. From September, 2003, to November, 2006, 70 consecutive patients with advanced, [...] Read more.
The activation of lymphocytes by gefitinib treatment has been described. In this phase II pilot trial, we explored the possible synergism between IL-2 and gefitinib for non-small cell lung cancer (NSCLC) treatment. From September, 2003, to November, 2006, 70 consecutive patients with advanced, progressive NSCLC, previously treated with chemotherapy, received oral gefitinib 250 mg daily. The first 39 patients received gefitinib alone (G group). The other 31 also received subcutaneous IL-2 (GIL-2 group): 1 MIU/m2 (Million International Unit/m2)twice a day on Days 1 and 2, once a day on Days 3, 4, 5 every week for four consecutive weeks with a four-week rest period. Median follow-up was 25.2 months. Grade 3–4 toxicity of gefitinib was represented by skin rash (7%), asthenia/anorexia (6%) and diarrhea (7%); patients treated with IL-2 showed grade 2–3 fever (46%), fatigue (21%) and arthralgia (13%). In the GIL-2 group and G-group, we respectively observed: an overall response rate of 16.1% (6.4% complete response) and 5.1% (only partial response); a disease control rate of 41.9% and 41%; a median time to progression of 3.5 (CI 95% = 3.2–3.8) and 4.1 (CI 95% = 2.6–5.7) months; a median overall survival of 20.1 (CI 95% = 5.1–35.1) and 6.9 (CI 95% = 4.9–8.9) months (p = 0.002); and an actuarial one-year survival rate of 54% and 30%. Skin toxicity (p < 0.001; HR = 0.29; CI 95% = 0.16–0.54) and use of IL-2 (p < 0.001; HR = 0.33; CI 95% = 0.18–0.60) were independently associated with improvement of survival. In this consecutive, non-randomized, series of advanced NSCLC patients, the use of IL-2 increased the efficacy of gefitinib. Full article
(This article belongs to the Special Issue Cancer Drug Resistance)
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1169 KiB  
Article
Circulating Biomarkers in Advanced Colorectal Cancer Patients Randomly Assigned to Three Bevacizumab-Based Regimens
by Antonia Martinetti, Rosalba Miceli, Elisa Sottotetti, Maria Di Bartolomeo, Filippo De Braud, Arpine Gevorgyan, Katia Fiorella Dotti, Emilio Bajetta, Manuela Campiglio, Francesca Bianchi, Giacomo Bregni and Filippo Pietrantonio
Cancers 2014, 6(3), 1753-1768; https://doi.org/10.3390/cancers6031753 - 29 Aug 2014
Cited by 16 | Viewed by 5830
Abstract
The need to identify biomarkers for bevacizumab-based treatment in advanced colorectal cancer is imperative. The aim of this study was to investigate the prognostic role of circulating VEGF, PDGF, SDF-1, osteopontin and CEA in patients randomly assigned to three bevacizumab-based regimens. Plasma samples [...] Read more.
The need to identify biomarkers for bevacizumab-based treatment in advanced colorectal cancer is imperative. The aim of this study was to investigate the prognostic role of circulating VEGF, PDGF, SDF-1, osteopontin and CEA in patients randomly assigned to three bevacizumab-based regimens. Plasma samples from 50 patients treated at a single Institution were analysed using the multiplex assay BioPlex™ 2200 (Bio-Rad Laboratories, Inc, Berkeley, CA, USA) at baseline, before first three cycles and subsequently every three cycles until disease progression. Prognostic analyses of baseline values were performed using multivariable Cox models, including disease extension >10 cm or ≤10 cm (measured as the sum of the diameters for all target lesions) as adjustment factor. The association between progression-free and overall survival and biomarkers modulation during treatment was studied using multivariable Cox models, which included summary statistics synthesizing during-treatment modulation together with disease extension. The biomarkers significantly associated with disease extension were baseline CEA (p = 0.012) and SDF-1 (p = 0.030). High values of VEGF and SDF-1 tended to be associated with worse prognosis, especially in terms of overall survival. The negative prognostic trend was more marked for baseline CEA as compared to other biomarkers; increasing values during treatment was significantly related to worse prognosis independently of disease extension (p = 0.007 and 0.016 for progression-free and overall survival, respectively). VEGF is related to bevacizumab pharmacodynamics and is associated to other angiogenic cytokines; some of the proposed biomarkers such as SDF-1 and CEA should be further validated for prognosis assessment and monitoring of bevacizumab-based treatment of advanced colorectal cancer. Full article
(This article belongs to the Special Issue Cancer Drug Resistance)
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Review

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633 KiB  
Review
Desmoplasia and Chemoresistance in Pancreatic Cancer
by Marvin Schober, Ralf Jesenofsky, Ralf Faissner, Cornelius Weidenauer, Wolfgang Hagmann, Patrick Michl, Rainer L. Heuchel, Stephan L. Haas and J.-Matthias Löhr
Cancers 2014, 6(4), 2137-2154; https://doi.org/10.3390/cancers6042137 - 21 Oct 2014
Cited by 112 | Viewed by 13485
Abstract
Pancreatic ductal adenocarcinoma (PDAC) occurs mainly in people older than 50 years of age. Although great strides have been taken in treating PDAC over the past decades its incidence nearly equals its mortality rate and it was quoted as the 4th leading cause [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) occurs mainly in people older than 50 years of age. Although great strides have been taken in treating PDAC over the past decades its incidence nearly equals its mortality rate and it was quoted as the 4th leading cause of cancer deaths in the U.S. in 2012. This review aims to focus on research models and scientific developments that help to explain the extraordinary resistance of PDAC towards current therapeutic regimens. Furthermore, it highlights the main features of drug resistance including mechanisms promoted by cancer cells or cancer stem cells (CSCs), as well as stromal cells, and the acellular components surrounding the tumor cells—known as peritumoral desmoplasia—that affects intra-tumoral drug delivery. Finally, therapeutic concepts and avenues for future research are suggested, based on the topics discussed. Full article
(This article belongs to the Special Issue Cancer Drug Resistance)
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1544 KiB  
Review
Repositioning of Tyrosine Kinase Inhibitors as Antagonists of ATP-Binding Cassette Transporters in Anticancer Drug Resistance
by Yi-Jun Wang, Yun-Kai Zhang, Rishil J. Kathawala and Zhe-Sheng Chen
Cancers 2014, 6(4), 1925-1952; https://doi.org/10.3390/cancers6041925 - 29 Sep 2014
Cited by 55 | Viewed by 11565
Abstract
The phenomenon of multidrug resistance (MDR) has attenuated the efficacy of anticancer drugs and the possibility of successful cancer chemotherapy. ATP-binding cassette (ABC) transporters play an essential role in mediating MDR in cancer cells by increasing efflux of drugs from cancer cells, hence [...] Read more.
The phenomenon of multidrug resistance (MDR) has attenuated the efficacy of anticancer drugs and the possibility of successful cancer chemotherapy. ATP-binding cassette (ABC) transporters play an essential role in mediating MDR in cancer cells by increasing efflux of drugs from cancer cells, hence reducing the intracellular accumulation of chemotherapeutic drugs. Interestingly, small-molecule tyrosine kinase inhibitors (TKIs), such as AST1306, lapatinib, linsitinib, masitinib, motesanib, nilotinib, telatinib and WHI-P154, have been found to have the capability to overcome anticancer drug resistance by inhibiting ABC transporters in recent years. This review will focus on some of the latest and clinical developments with ABC transporters, TKIs and anticancer drug resistance. Full article
(This article belongs to the Special Issue Cancer Drug Resistance)
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427 KiB  
Review
Drug Resistance in Cancer: An Overview
by Genevieve Housman, Shannon Byler, Sarah Heerboth, Karolina Lapinska, Mckenna Longacre, Nicole Snyder and Sibaji Sarkar
Cancers 2014, 6(3), 1769-1792; https://doi.org/10.3390/cancers6031769 - 05 Sep 2014
Cited by 1695 | Viewed by 49605
Abstract
Cancers have the ability to develop resistance to traditional therapies, and the increasing prevalence of these drug resistant cancers necessitates further research and treatment development. This paper outlines the current knowledge of mechanisms that promote or enable drug resistance, such as drug inactivation, [...] Read more.
Cancers have the ability to develop resistance to traditional therapies, and the increasing prevalence of these drug resistant cancers necessitates further research and treatment development. This paper outlines the current knowledge of mechanisms that promote or enable drug resistance, such as drug inactivation, drug target alteration, drug efflux, DNA damage repair, cell death inhibition, and the epithelial-mesenchymal transition, as well as how inherent tumor cell heterogeneity plays a role in drug resistance. It also describes the epigenetic modifications that can induce drug resistance and considers how such epigenetic factors may contribute to the development of cancer progenitor cells, which are not killed by conventional cancer therapies. Lastly, this review concludes with a discussion on the best treatment options for existing drug resistant cancers, ways to prevent the formation of drug resistant cancers and cancer progenitor cells, and future directions of study. Full article
(This article belongs to the Special Issue Cancer Drug Resistance)
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