Special Issue "Cancer Diagnosis and Targeted Therapy"
QuicklinksA special issue of Cancers (ISSN 2072-6694).
Deadline for manuscript submissions: closed (31 January 2011)
Special Issue Editor
Guest Editor
Dr. Veronique Baud
1 Institut Cochin, Centre national de la recherche scientifique (CNRS) UMR 8104, Inserm U1016, Paris, France
2 Immunology-Hematology Department, Université Paris Descartes, 123 Boulevard de Port-Royal, 75014 Paris, France
Website: http://cochin.inserm.fr/research/scientific-departments/ih/team
E-Mail:
Interests: interface between signal transduction and cancer with a focus on the alternative NF-kappaB signaling pathway, how it is regulated, and its contributions towards tumor development and resistance to conventional cancer therapies
Published Papers
Special Issue Information
Dear Colleagues,
Although mortality rates have declined in recent years, the majority of cancers are still difficult to treat and the medical need for better cancer treatment is evident. The current anticancer armamentarium includes many active agents that are applied across tumor types, and most drugs have a small therapeutic index and barely discriminate between malignant and normal cells. In recent years the focus has shifted to the development of rationally designed, molecularly-targeted therapy for the treatment of a specific cancer, therefore offering the promise of greater specificity coupled with reduced systemic toxicity. Another challenge has been the development of prognostic and pharmacogenomic biomarkers that enable the targeting of individualized treatments to those patients most likely to benefit.
This special issue will explore the routes from cancer research and oncogenomics into the development of novel mechanism-based cancer therapeutics and biomarkers.
We invite research and review papers in any area of oncology that are related, but not limited to, fundamental understanding of oncogenomics and cancer signaling pathways, diagnostic, prognostic and pharmacogenomic biomarkers, molecular diagnosis by gene expression profiling, molecular targets driving the progression of human cancers, cancer drug development on these targets, clinical trial with new agents, validation in animal models.
Dr. Veronique Baud
Guest Editor
Submission
Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.
Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed Open Access quarterly journal published by MDPI.
Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 500 CHF (Swiss Francs). English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.
Keywords
- cancer targeted diagnosis
- cancer targeted therapeutics
- solid tumors
- hematological malignancies
- oncogenomics
- gene expression profiling
- molecular targets
- mechanism-based drug development
- biomarkers
- miRNA
- ubiquitin-proteasome pathway
- clinical trials
- animal models
Planned Papers
Type of Paper: Review
Title: Targeted Therapy in Nonmelanoma Skin Cancers
Authors: Giulia Spallone, Elisabetta Botti and Antonio Costanzo
Affiliation: Department of Dermatology, University of Rome “Tor Vergata”, Rome, Italy;
E-Mail: antonio.costanzo@uniroma2.it
Abstract: Nonmelanoma skin cancer (NMSC) is the most prevalent cancer in the light-skinned population, and include mainly Basal Cell Carcinomas (BCC), representing around 75% of NMSC and Squamous Cell Carcinomas (SCC). The incidence of these tumors is continuosly growing. It was found that the overall number of procedures for NMSC in US rose by 76%, from 1,158,298 in 1992 to 2,048,517 in 2006. Although mortality from NMSC tends to be very low, clearly the morbidity related to these skin cancers is very high. Treatment options for NMSC include both surgical and nonsurgical interventions. Surgery was considered the gold standard therapy however, advancements in the knowledge of pathogenic mechanisms of NMSCs led to the identification of key targets for drug intervention and to the consequent development of several targeted therapies. These represent the future in treatment of these common form of cancer ensuring high cure rate, preservation of the maximal amount of normal surrounding tissue and optimal cosmetic outcome. Here, we will review recent advancements in NMSC targeted therapies focusing on BCC.
Type of Paper: Review
Title: Neuropilin 2: A New Candidate for Targeted Therapies in Gastrointestinal Cancers
Authors: Camille Grandclement1,2,3,and Christophe Borg1,2,3,4
Affiliations: 1 INSERM UMR 645, F-25020, Besançon, France
2 University of Franche-Comté, IFR133, F-25020 Besançon, France
3 EFS Bourgogne Franche-Comté F-25020, Besançon, France
4 CHU Besançon, CIC-BT 506, Department of Medical Oncology, 25000 Besançon, France; E-Mail: camille.grandclement@gmail.com (C.G.)
Abstract: Recent investigations highlighted strong similarities between neural crest migration during embryogenesis and metastasis processes. Indeed, some families of axon guidance molecules were also reported to participate in cancer invasion: plexins/semaphorins/neuropilins, ephrins/ Eph receptors, netrin/DCC/UNC5. Neuropilins (NRPs) are transmembrane non tyrosine-kinase glycoproteins first identified as receptors for class-3 semaphorins. They are particularly involved in neural crest migration and axonal growth during development of the nervous system. Since many types of tumoral and endothelial cells express NRPs receptors, various soluble molecules were also found to interact with these receptors to modulate cancer progression. Among them, angiogenic factors belonging to the Vascular Endothelial Growth Factor (VEGF) family seem to be responsible for NRPs-related angiogenesis. Because NRPs expression is often upregulated in cancer tissues and correlated with poor prognosis, NRPs expression might be considered as a prognostic factor. While NRP1 was intensively studied from many years and identified as an attractive angiogenesis target for cancer therapy, NRP2 signaling pathway has just recently been studied. Although, NRPs genes share 44% homology, sensible differences in their expression patterns, ligands specificities or signaling pathways were observed. Indeed, NRP2 may regulate tumor progression by several concurrent mechanisms, not only angiogenesis but lymphangiogenesis, epithelial-mesenchymal transition and metastasis too. In view of its multiples functions in cancer promotion, NRP2 fulfills all the criteria of a therapeutic target for innovative anti-tumor therapies. This review proposes a focus on NRP2 specific roles in tumor progression.
Type of Paper: Article
Title: A Methodological Framework for Evaluating the Evidence for Complementary and Alternative Medicine (CAM) in Cancer
Authors: Robert Zachariae 1, Helle Johannessen 2
Affiliations: 1 Psychooncology Research Unit, Department of Oncology, Aarhus University Hospital and Department of Psychology, University of Aarhus, Aarhus, Denmark
2 Research Unit Health, Man & Society, Institute of Public Health, University of Southern Denmark, Odense, Denmark; E-Mail: hjohannessen@health.sdu.dk
Abstract: In spite of lacking evidence for effects on cancer progression itself, an increasing number of cancer patients use various types of complementary and alternative medicine (CAM), and there is disagreement between CAM practitioners, researchers and clinical oncologists, as to how evidence concerning effects of CAM can and should be produced, and how the existing evidence should be interpreted. This represents a considerable challenge for oncologists, both in terms of patient needs for an informed dialogue regarding CAM, and because some types of CAM may interact with standard treatments. There is a need for insight into what kinds of CAM may work, for whom they work, what the possible effects and side-effects are, and in what ways such effects may come about. The present article presents a framework for evaluating effects of CAM by suggesting a taxonomy of different levels of evidence related to different types of research questions and discussing the relevance of different research methodologies for different types of effects.
Type of Paper: Review
Title: Over diagnosis and Long Term Effects in Cancer Screening
Authors: Dongfeng Wu 1 and Kathy B. Baumgartner 2
Affiliations: 1 Department of Bioinformatics and Biostatistics, School of Public
Health and Information Sciences, University of Louisville, Louisville, KY 40202, USA; E-Mail: dongfeng.wu@louisville.edu
2 Department of Epidemiology, School of Public Health and Information, Sciences, University of Louisville, Louisville, KY 40202, USA; E-Mail: kbbaum01@gwise.louisville.edu
Abstract: Cancer screening programs have been effective in detecting tumors early before symptoms are present. However, a challenge remains as to how to evaluate the long-term effects due to continued regular screening. Some research has been done in the area of over-diagnosis, the diagnosis of cancer that never becomes symptoms in a patient's life time. However, most of the research has been based on observational studies. The research has been partially correct or biased due to lack of probability modeling. The estimated percentage of over-diagnosis varies from 7% to 52%. A new probability model was developed recently to address the long-term effects due to regular screening. Participants in a periodic screening program can be classified into four mutually exclusive groups: True-early-detection, No-early-detection, Over-diagnosis, and Not-so-necessary, depending on whether individuals would be diagnosed with the specific cancer and whether their symptoms would have appeared before death. We will review some major development in this area, and some summary result in breast cancer screening.
Keywords: cancer screening; over diagnosis; true early detection; long term effect.
Type of Paper: Review
Title: NF-kappaB in T-cell acute lymphoblastic leukemia: leukemogenic functions in leukemic and in microenvironmental cells
Authors: Nuno R. dos Santos, Marinella N. Ghezzo, Ricardo C. da Silva and Mónica T. Fernandes
Affiliation: IBB-Institute for Biotechnology and Bioengineering, Centre for Molecular and Structural Biomedicine (CBME), University of Algarve, Campus de Gambelas, 8005-139 Faro, Portugal; E-Mail: nrsantos@ualg.pt
Abstract: Two main NF-kappaB signaling pathways, canonical and noncanonical, performing distinct functions in organisms have been characterized. Identification of mutations in genes encoding components of these NF-kappaB signaling pathways in lymphoid malignancies confirmed their key role in leukemogenesis. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of thymocytes that despite significant therapeutic advances can still be fatal. Although mutations in NF-kappaB genes have not been reported in T-ALL, NF-kappaB constitutive activation in human T-ALL and in acute T-cell leukemia mouse models has been observed. Although these studies revealed activation of members of both canonical and noncanonical NF-kappaB pathways in acute T-cell leukemia, only inhibition of canonical NF-kappaB signaling was shown to impair leukemic T cell growth. Besides playing an important pro-oncogenic role in leukemic T cells, NF-kappaB signaling also appears to modulate T-cell leukemogenesis through its action in microenvironmental stromal cells. This article reviews recent data on the role of these transcription factors in T-ALL and pinpoints further research crucial to determine the value of NF-kappaB inhibition as a means to treat T-ALL.
Type of Paper: Article
Title: Survival Analysis According to Mode of Breast Cancer Detection and Diagnosis Delay
Authors: Anna Crispo, Maria Grimaldi, Massimo Rinaldo, Katerina Tsapakina, Giuseppina Caolo, MariaRosaria De Marco, Massimiliano D’Aiuto, Giuseppe D’Aiuto, Gerardo Botti, Alfonso Amore and Maurizio Montella
Affiliation: Department of Epidemiology, National Cancer Institute, G. Pascale Foundation, Via M. Semmola, 80131 Naples, Italy;
E-Mail: epidemiologia.int@alice.it
Abstract: Several studies have recently focused on the association between mode of breast cancer detection and breast cancer prognosis; they described a more favorable prognosis for mammography-detected breast cancer than for cancer detected with other methods. Moreover consistent evidence shows that delays in breast cancer diagnosis may affect disease stage and influence survival. We investigated the differences between mode of breast cancer detection and diagnosis delay on the time to relapse after surgery (disease-free survival [DFS], Disease-free survival refers to the proportion of patients alive and without disease over a specific period of time) in our patients case-series. The follow-up period was from January 2004; using a recently published multicenter breast cancer dataset, we selected the patients from NCI of Naples who completed their follow-up (N=398). A slight significant difference was observed for women whose breast cancer was detected by mammography (MG) compared to women whose breast cancer was self-detected (S-D) (p=0.05) and for diagnostic delay (0.01). We found evidence of a significant association between mode of breast cancer detection and diagnosis delay in histologically confirmed breast cancer patients. The diagnosis delay also influences the disease-free survival and overall survival.
Abstract: Current clinical trials of epidermal growth factor receptor (EGFR)-targeted therapies are mostly guided by a classical approach coming from the cytotoxic paradigm. The predominant view is that the efficacy of EGFR antagonists correlates with skin rash toxicity and induction of objective clinical response. Clinical benefit from EGFR-targeted therapies is well documented, however, chronic use in advanced cancer patients has been limited due to cumulative and chemotherapy-enhanced toxicity. Here we analyze different pieces of data from mechanistic and clinical studies with the anti-EGFR monoclonal antibody Nimotuzumab, which provide some clues to understand how this antibody may induce a biological control of tumor growth while keeping a low toxicity profile. Based on these results and the current state of the art on EGFR-targeted therapies, we discuss the need to evaluate new therapeutic approaches using anti-EGFR agents, which would have the potential of transforming advanced cancer into a long-term controlled chronic disease.
Type of Paper: Review
Authors: Sujeet Kumar 1,2, Jonathan R Dimmock 3 and Rajendra K Sharma 1,2
Affiliations: 1 Department of Pathology and Laboratory Medicine, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5C9, Canada; E-Mail: rajendra.sharma@saskcancer.ca (R.S.)
3 College of Pharmacy and Nutrition, 110 Science Place, University of Saskatchewan, Saskatoon, SK S7N 5C9, Canada
Abstract: Colon cancer is one of the most common malignant diseases and a major cause of mortality in the western world. Metastasis to lymph nodes and other gastrointestinal organs, especially to the liver and lungs is most common and occurs in up to 25% of cancer patients when initially diagnosed. The majority of colon cancers develop from noncancerous adenomatous polyps on the lining of the colon which grows over the years to become cancerous. If detected early, the surgical resections of the growth, often in combination with chemotherapy, significantly increases life expectancy. We have showed that the enzyme N-myristoyltransferase (NMT) which carries out lipid modification of several proteins (including many of those involved in oncogenesis) is expressed at higher levels in cancerous tissue from the colon. We have also shown that in peripheral blood mononuclear cells (PBMC) and bone marrow collected from the colon cancer patients and azoxymethane induced rats the expression and localization of NMT is altered. We have observed strong positivity for NMT in immunohistochemical analysis for PBMC from colon cancer patients as compared to control groups. Furthermore in the bone marrow (BM) mononuclear cells NMT was found to be confined to the nuclei whereas in control groups it was observed to be located in the cytoplasm. In conclusion, the strikingly differential localization offers the basis of a potential investigational tool for screening or diagnosis of individuals at risk for or suspected of having colon cancer.
Type of Paper: Review
Title: Monoclonal Antibodies in Hematological Malignancies: Past, Present and Future
Authors: I. Tazi, H. Nafil, L. Mahmal and M. Harif
Affiliation Hematology Department, Chu Mohamed Vi, Cadi Ayyad, University Marrakech, Morocco; E-Mail: tazi_illias@hotmail.com
Abstract: Much progress has been made during the last few decades in the treatment of haematological malignancies. Monoclonal antibodies (MoAbs) represent a major advance towards a targeted therapy that can dramatically improve the anti-tumour effect with a substantial reduction of toxicity derived from therapy. Unlike many small molecules, MoAbs offer unique target specificity. Several monoclonal antibodies are now in clinical use for hematologic malignancies therapy, and many others are currently undergoing clinical evaluation. This review summarizes the state-of-the-art MoAbs treatment, beginning with an overview of the scientific background to their synthesis, mechanism of action and choice of target antigen, mainly focusing on those antibodies that are currently in use in clinical practice. Despite these advances, significant challenges remain in the identification of optimal cellular targets, antibody forms and treatment schedules for therapeutic applications.
Type of Paper: Review
Title: Recent Advance in Biosensors for MicroRNAs Detection in Cancer
Authors: CL. Esposito, S. Catuogno, L. Cerchia, G. Condorelli and V. de Franciscis
Affiliation: Istituto per l’Endocrinologia e l’Oncologia Sperimentale del CNR ‘‘G. Salvatore’’, Via S. Pansini 5, 80131 Naples, Italy;
E-Mail: defranci@unina.it (V.d.F.)
Abstract: MiRNAs (miRNAs) are 19–25 nucleotides regulatory non protein-coding RNA molecules that regulate the expressions of a wide variety of genes by sequence-specific base pairing on the 3’ untranslated regions (3’UTR) of the target mRNA resulting in mRNA degradation or inhibition of translation.Recent studies have implicated them in a wide range of biological processes and diseases including development, metabolism, and cancer, revealing that some miRNAs or patterns of miRNAs expressed may serve as molecular biomarkers for cancer diagnostics and prognostic. Therefore, a major challenge is to develop innovative quantitative bioanalytical methods to rapidly detect miRNAs present in a particular cell or tissue with high sensitivity and specificity. In this review, we will discuss the latest innovative approaches proposed for miRNA profiling in cancer. These will include: improvement of microarray based- microRNA profiling as well as the development of label-free innovative strategies as Surface enhanced Raman scattering, silicon nanowires devices and electrochemical genosensors.
Type of Paper: Review
Title: Differentiation Therapy of Acute Myeloid Leukemia
Authors: Elzbieta Gocek and Ewa Marcinkowska
Affiliation: Department of Biotechnology, University of Wroclaw, Wroclaw, Poland; E-Mail: ewa@protein.pl (E.M.)
Abstract: Acute Myeloid Leukemia (AML) is a predominant acute leukemia among adults, characterized by accumulation of malignantly transformed immature myeloid precursors. A very attractive way to treat myeloid leukemia, which is now called ‘differentiation therapy’, was proposed when in vitro studies have shown that a variety of agents stimulate differentiation of cell lines isolated from leukemic patients. One of the differentiation-inducing agents, all-trans retinoic acid (ATRA), which can induce granulocytic differentiation in myeloid leukemic cell lines, has been introduced into clinics to treat patients with acute promyelocytic leukemia (APL) in which a PML-RAR fusion protein is generated by a t(15;17)(q22;q12) chromosomal translocation. Because differentiation therapy of APL using ATRA has significantly improved prognosis for patients with APL, many efforts have been made to find alternative differentiating agents. Since 1,25-dihydroxyvitamin D3 (1,25D) is capable of inducing in vitro monocyte/macrophage differentiation of myeloid leukemic cells, clinical trials have been performed to estimate its potential to treat patients with AML or myelodysplastic syndrome (MDS). Unfortunately therapeutic concentrations of 1,25D can induce potentially fatal systemic hypercalcemia, thus limiting clinical utility of that compound. Attempts to overcome this problem have focused on the synthesis of 1,25D analogs (VDAs) which retain differentiation inducing potential, but lack its hypercalcemic effects. This review aims to discuss current problems and potential solutions in differentiation therapy of AML.
Type of Paper: Review
Title: Targeted Therapy for Biliary Tract Cancer
Author: Junji Furuse
Affiliations: Department of Internal Medicine, Medical Oncology, Kyorin University School of Medicine, 6-20-2, Shinkawa, Mitaka,Tokyo, 181-8611, Japan;
E-Mail: jfuruse@ks.kyorin-u.ac.jp
Abstract: It is necessary to establish effective chemotherapy to improve the survival in patients with biliary tract cancer, because most of those patients are unsuitable candidates for surgery and even patients undergoing currative surgery often have recurrence. Recently, the combination of cisplatin and gemcitabine (Cis/Gem therapy) was reported to show survival benefits over gemcitabine alone in randomized clinical trials conducted in the United Kingdom and Japan. As a result, Cis/Gem therapy is now recognized as the standard therapy for unresectable biliary tract cancer. One of the next issues that need to be addressed is whether molecular targeted agents might also be effective for biliary tract cancer. Although some targeted agents were investigated as monotherapy for first-line chemotherapy, they were not found to exert satisfactory efficacy. On the other hand, monoclonal antibodies such as bevacizumab and cetuximab have also been investigated in combination with a gemcitabine-based regimen, and been demonstrated to show promising activity. Furthermore, clinical trials using new targeted agents for biliary tract cancer are also proposed. This cancer is a relatively rare and heterogenous tumor consisting of cholangiocarcinoma and gallbladder carcinoma. Therefore, a large randomized clinical trial is necessary to confirm the efficacy of chemotherapy and international collaboration is important.
Type of Paper. Article
Title: Common Symptoms and Distresses Experienced among Patients with Colorectal Cancer: An Interview Study
Authors: Sussanne Börjeson1,2, Mitra Unosson1,3, Hans Starkhammar2 Carina Berterö1
Affiliations: 1Department of Medical and Health Sciences, Division of Nursing Science, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden; E-Mail: carina.bertero@liu.se
2Department of Oncology, Linköping University Hospital, SE- 581 85 Linköping, Sweden
3 Department for studies on society and welfare, Division of Health, Activity and Care, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden
Abstract: The present study was designed to qualitatively identify and describe the most common symptoms among patients diagnosed with colorectal cancer and if there are any barriers to report any symptoms or distresses. Data was collected by qualitative interviews where the patient’s lived experiences were articulated. Thirteen Swedish patients diagnosed with colorectal cancer and being treated with chemotherapy was interviewed. The interviews were audio-taped and transcribed verbatim. All the transcripts were analyzed through a continuous process of reading the text and following the principles of qualitative content analysis. The analysis identified nine symptoms/distresses. Those most frequently expressed were changed bowel habits, fatigue and affecting humour and mental well-being, closely followed by nausea, loss of appetite and neurological distresses. The remaining symptoms/distresses were expressed by almost half ofthe patients or below. Barriers for symptom control were only expressed by the patients by the way and very vague. Discussion/reflection and conclusion drawn is under progress.
Keywords: Colorectal cancer, symptoms, patient’s experiences, barriers
Type of Paper: Review
Title: Targeted Therapy for Biliary Tract Cancer
Author: Junji Furuse
Affiliations: Department of Internal Medicine, Medical Oncology, Kyorin University School of Medicine, 6-20-2, Shinkawa, Mitaka,Tokyo, 181-8611, Japan; E-Mail: jfuruse@ks.kyorin-u.ac.jp
Abstract: It is necessary to establish effective chemotherapy to improve the survival in patients with biliary tract cancer, because most of those patients are unsuitable candidates for surgery and even patients undergoing currative surgery often have recurrence. Recently, the combination of cisplatin and gemcitabine (Cis/Gem therapy) was reported to show survival benefits over gemcitabine alone in randomized clinical trials conducted in the United Kingdom and Japan. As a result, Cis/Gem therapy is now recognized as the standard therapy for unresectable biliary tract cancer. One of the next issues that need to be addressed is whether molecular targeted agents might also be effective for biliary tract cancer. Although some targeted agents were investigated as monotherapy for first-line chemotherapy, they were not found to exert satisfactory efficacy. On the other hand, monoclonal antibodies such as bevacizumab and cetuximab have also been investigated in combination with a gemcitabine-based regimen, and been demonstrated to show promising activity. Furthermore, clinical trials using new targeted agents for biliary tract cancer are also proposed. This cancer is a relatively rare and heterogenous tumor consisting of cholangiocarcinoma and gallbladder carcinoma. Therefore, a large randomized clinical trial is necessary to confirm the efficacy of chemotherapy and international collaboration is important.
Type of Paper: Review
Title: Activity of Tyrosine Kinase Inhibitors on Neuroblastoma Cells
Author: Fabio Timeus
Affiliation: Pediatric Onco-hematology, Ospedale Infantile Regina Margherita, Torino, Italy; E-Mail: fabio.timeus@unito.it
Abstract: Neuroblastoma (NB) is the second more frequent solid tumor in childhood. In spite of very aggressive treatments, the prognosis of its advances stages is still poor, so there is interest for alternative therapeutic strategies. In the last years the use of the bcr/abl tyrosine kinase inhibitor (TKi) imatinib has radically changed the therapeutic approach to chronic myeloid leukemia (CML) and Ph positive acute lymphoblastic leukemia. Due to its activity on other TK receptors as c-kit and PDGFR, imatinib has been successfully utilized in the therapy of chronic eosinophilic leukemia and gastrointestinal stromal tumors (GIST). Years ago, several studies have demonstrated the expression of c-kit and PDGFR in NB cell lines and in primary NB samples, giving the rationale to explore the activity of TKi in these tumor cells. Various studies have described an in vitro dose-dependent anti-proliferative and pro-apoptotic activity of imatinib in NB cell lines. This activity was associated with the inhibition of ligand-induced phosphorylation of c-kit and PDGFR. Imatinib also inhibited NB growth in mice. In this model the gene expression profiles of tumor masses suggested the accumulation of reactive oxygen species (ROS) resulting in cell death. The lack of a significant correlation between the levels of expression of c-kit and PDGFR in NB cells and the in vitro and in vivo sensitivity to the antitumor activity of imatinib suggested the involvement of other tyrosine kinases and/or pathways. A recent study described a significant antiproliferative and pro-apoptotic effect of protracted low-doses of imatinib on NB lines. This activity was also demonstrated in xenograft models and was synergistic with doxorubicin. Other Authors observed synergism between imatinib and retinoids.So far two phase II clinical studies on the use of imatinib in refractory or relapsed solid tumors including neuroblastoma lacked to demonstrate a significant in vivo anti-neuroblastoma activity in such advanced stages. Dasatinib is an inhibitor of TK and SRC-family kinases, utilized as second-line treatment of CML. Dasatinib exerted a significant anti-proliferative and anti-migratory activity in NB lines and partially inhibited tumor growth in nude mice. In conclusion, TKi exert a significant anti-NB activity in vitro and in vivo xenograft models. The in vitro efficacy of protracted low-dose treatment schedules and the anti-migratory activity on NB cells suggest a possible use of TKi in the therapy of NB.
Type of Paper: Review
Title: Biomarkers-IgM Immune Complexes: From the Discovery to the Assessment of the Clinical Role in Cancer
Authors: L. Beneduce, A. Gallotta, P. Pengo and G. Fassina
Affiliation: XEPTAGEN S.p.A., Via delle Industrie 9, 30175 Marghera Venezia, Italy; E-Mail: beneduce@xeptagen.com (L.B.)
Abstract: Pentameric IgM plays an important role in the immunosurveillance against cancer cells growth likely due to its high avidity toward cancer-associated marker as evidenced in different human tumors where several biomarkers can be detected bound to IgM to constitute immune complexes. In many different types of cancers, including hepatocellular carcinoma, colorectal, oesophageal, and prostate cancer but also in liver and lung fibrosis, this novel class of biomarkers-IgM immune complexes has shown a clinical value higher than and synergic to the corresponding free biomarkers. Assessment of serum concentration of biomarkers-IgM immune complexes has proved to be a useful approach for many purposes including early diagnosis, risk assessment, prognosis prediction, selection of appropriate treatments and reduction of the invasiveness and medical cost associated to certain diagnostic procedures. The remarkable feature which characterizes this novel class of biomarkers is the dynamic correlation of serum levels to tumor progression or to the response to therapeutic treatment, opening new gateways to improve the management and cost-effective monitoring of patients’ disease status.
Title: Molecular Predictive Factors of Sensitivity and Resistance to EGFR-Targeted Therapeutics in Colorectal Cancer
Author: Andrea Sartore-Bianchi
Affiliation: S.C. Divisione Oncologia Medica Falck, Dipartimento Oncologico, Ospedale Niguarda Ca' Granda, Piazza Ospedale Maggiore 3, 20162 Milano, Italy; E-Mail: Andrea.SartoreBianchi@OspedaleNiguarda.it (L.S.-B.)
Last update: 28 February 2011