Aims & Scope
Current Gene Therapy is a bi-monthly peer-reviewed journal aimed at academic and industrial scientists with an interest in major topics concerning basic research and clinical applications of gene and cell therapy of diseases. Cell therapy manuscripts can also include application in diseases when cells have been genetically modified. Current Gene Therapy publishes reviews and original research on the latest developments in gene transfer and gene expression analysis, vector development, cellular genetic engineering, animal models and human clinical applications of gene and cell therapy for the treatment of diseases.
Current Gene Therapy publishes reviews and original research containing experimental data on gene and cell therapy. The journal also includes manuscripts on technological advances, ethical and regulatory considerations of gene and cell therapy. Reviews should provide the reader with a comprehensive assessment of any area of experimental biology applied to molecular medicine that is not only of significance within a particular field of gene therapy and cell therapy but also of interest to investigators in other fields. Authors are encouraged to provide their own assessment and vision for future advances. Reviews are also welcome on late breaking discoveries on which substantial literature has not yet been amassed. Such reviews provide a forum for sharply focused topics of recent experimental investigations in gene therapy primarily to make these results accessible to both clinical and basic researchers. Manuscripts containing experimental data should be original data, not previously published.
Author(s): Samia M. O`Bryan, J. Michael Mathis*.
Breast cancer continues to be a leading cause of mortality among women. While at an early stage, localized breast cancer is easily treated; however, advanced stages of disease continue to carry a high mortality rate. The discrepancy in treatment success highlights that current treatments are insufficient to treat advanced-stage breast cancer. As new and improved treatments have been sought, one therapeutic approach has gained considerable attention. Oncolytic viruses are uniquely capable of targeting cancer cells through intrinsic or engineered means. They come in many forms, mainly from four major virus groups as defined by the Baltimore classification system. These vectors can target and kill cancer cells, and even stimulate immunotherapeutic effects in patients. This review discusses not only individual oncolytic viruses pursued in the context of breast cancer treatment but also the emergence of combination therapies with current or new therapies, which has become a particularly promising strategy for treatment of breast cancer. Overall, oncolytic virotherapy is a promising strategy for increased treatment efficacy for advanced breast cancer and consequently provides a unique platform for personalized treatments in patients.
Background: The evolutionarily conserved Hedgehog (Hh) signaling cascade is one of the key mediators of embryonic development of many metazoans. This pathway has been extensively targeted by small molecule inhibitors as its misregulation leads to various malignancies and developmental disorders. Thus, blocking this pathway can be a novel therapeutic avenue for the treatment of Hedgehog-dependent cancers. This review covers the mechanism of hedgehog signaling in vertebrate cells, provides an overview of reported small molecule Hh pathway inhibitors, with the synthetic routes and SAR studies of some of them discussed briefly.
Methods: A comprehensive survey of literature related to synthetic and naturally occurring Hh signaling antagonists reported till date is presented.
Results: Given the selectivity of small molecules targeting, this pathway for cancer treatment compared to kinase, tubulin or HDAC inhibitors, several such antagonists have been discovered, of which some are in preclinical development and clinical studies. Most of the reported small molecules primarily antagonize the Smoothened receptor although agents targeting Gli1 transcription factor and Shh ligand have also been discovered. Till date, nine Smo antagonists have been evaluated in clinical trials.GDC- 0449/Vismodegib and NVP-LDE225/Erismodegib, were granted approval by the U.S. Food and Drug Administration (U.S. FDA) for the treatment of basal cell carcinoma.
Conclusion: The challenge is to identify agents that target the pathway downstream of Smo and develop strategies to overcome acquired drug resistance to the current Smo inhibitors with deeper understanding of the resistance mechanisms.
ARTICLE BY DISEASE ON “BASAL CELL CARCINOMA”
Background: Long-term immunosuppressive therapy, as provided to solid organ transplant recipients, inevitably results in a significant inhibition of immune defenses; this leads to frequent skin infections and malignancies, which represent an important cause of morbidity and mortality for transplanted patients. The incidence and risk of skin carcinomas are elevated in solid organ transplant recipients in comparison with the general population, with a 10-fold increased risk for basal cell carcinoma and a 50-100-fold for squamous cell carcinoma. The schedule of immunosuppressive drugs influences the type and timing of skin malignancies, but a crucial role is also played by endogenous and exogenous risk factors.
Methods & Results: Here, we will review the state-of-the-art in chemoprevention of epidermal carcinomas in order to provide useful information for clinicians involved in the management of transplant recipients. One-hundred and forteen paper, published on peerreviewed journals, has been included.
Conclusion: Chemoprevention would be key in controlling skin carcinogenesis in high-risk patients.
Rising Above Local Competition Through Optimisation of Operationally Efficient, Specifically Targeted Oncology Clinical Trials
14th & 15th November 2018, Munich, Germany
As the only operationally focused oncology conference in Europe this two-day event is a must attend! After huge success in 2017, the Clinical Operations in Oncology Trials Europe Conference will be returning to Munich for its 5th edition, with more interactive content and senior level speakers than before.
The 2018 programme will host speakers from the likes of Roche, AstraZeneca, Celyad, Bayer, Karma Oncology and Zelluna Immunotherapy.
Highlights from this years’ agenda include a practical workshop on strengthening collaboration through vendor management; a global project leader discussing how and why patients should be involved in protocol design; and a technology spotlight session where we will discover how digital platforms can be successfully integrated into oncology trials.
This conference provides a networking platform to discuss key issues with your fellows, facilitating the formation of new partnerships and strengthening existing relationships.
CTO Europe will be returning on 14th & 15th November to Munich. Please get in touch if you are interested in taking part!
20% DISCOUNTS ON PURCHASING EBOOKS AND SUBSCRIPTIONS ON JOURNALS FROM BENTHAM SCIENCE TO DELEGATES ATTENDING THE CONFERENCE
ARTICLE BY DISEASE ON ” ANAL CANCER “
EGFR is the cell-surface receptor. Its overexpression or overactivity has been associated with a number of cancers, including breast, lung, ovarian, and anal cancers. Many therapeutic approaches are aimed at the EGFR. A series of 2, 7-diamino-thiazolo [4,5-d] pyrimidine analogues are among the most highly potent and selective inhibitors of EGFR described to date. For in-depth investigation into the structural and chemical features responsible for the binding recognition mechanism concerned, as well as for exploring the binding pocket of these compounds, we performed a series of automated molecular docking operations. It was revealed that the binding site consisted of three main areas (P1, P2 and P3) composed of most of the hydrophobic amino acids able to accommodate the lipophilic arms of the compounds investigated. However, the solvent interface did not make much contribution to the binding of the inhibitors. The presence of residues Met793 and Asp855 may also be responsible for the binding recognition through H-bond interactions, with Phe856 through a T-shape π-π stacking interaction. The interaction model and pharmacophore of EGFR inhibitors were derived that can be successfully used to explain the different biologic activities of these inhibitors. Moreover, the docking results were quite robust as further validated by molecular dynamics. It is anticipated that the findings reported here may provide very useful information or clue for designing effective drugs for the therapeutic treatment of EGFR-related cancer.
ARTICLE BY DISEASE ON “ANAL CANCER”
Anal cancer represents an increasing health problem, especially in immune-compromised patients, as HIVpositive patients. Notably, a significant higher incidence rate is reported among HIV infected patients with the advent of highly active antiretroviral therapy (HAART). To date, no randomised trial supports the correlation between existing screening strategies and reduced progression of anal intraepithelial neoplasia (AIN) to anal cancer or improved survival. Nevertheless, screening and treatment of AIN by topical agents should be implemented in high risk population. Data on invasive anal cancer treatment show that combined modality treatment (CMT) is the treatment of choice. Early reports on HIV-positive patients describe higher treatment toxicity and a relation with lower CD4 count and higher HIV viral load. More recently, reported outcomes seem to be similar in HIV-positive population and general population. Reports on a rise in local recurrence rates and in acute side effects along with a correlation with pre-treatment CD4 counts in HIV-positive patients, are not confirmed by all authors. The development of the first approved vaccine is a milestone in the field of anogenital cancers. However, many questions are still unresolved especially as concerns immunization in the setting of HIV infection.