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Targeted Gene Therapy of Cancer

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 April 2022) | Viewed by 14193

Special Issue Editor


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Guest Editor
Faculty of Medicine, Department of Brain Sciences, Imperial College London, London W12 0NN, UK
Interests: cancer targeted therapies; bacteriophage gene delivery; gene therapy; cancer immunotherapy; vaccine delivery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Gene therapy offers a potential treatment strategy against cancer and has been attempted for many decades, with most of clinical trials (67%) of gene therapy are designed to treat cancer. However, progress has been hindered mostly by lack of tumor-selective vectors efficient via clinical systemic routes. Systemic administration of a vector, illustrating safe, efficient, and targeted gene delivery to tumors has proven to be a major challenge. Local delivery can be used but wider clinical benefit requires systemic administration of gene therapy. For instance, treatment of metastatic cancer, responsible for as much as 90% of cancer-related deaths, is heavily reliant upon systemically administered therapeutics. Gene therapy has been further hampered by problems with repeated vector administrations, which are crucial to achieve and sustain a therapeutic response. Systemic delivery using eukaryotic viruses has faced challenges due to undesired uptake by the liver and reticulo-endothelial system, broad tropism for normal tissues, insertional mutagenesis and immunogenicity limiting repeated vector delivery. It is obvious that a successful systemic gene therapy will depend on the successful design of targeted delivery vectors able to express therapeutic genes in the tumor tissue following systemic administration while sparing the healthy tissues. The present Special Issue aims to introduce the potential of targeting gene therapy to cancer and the role of nucleic acid delivery technologies that could present a breakthrough in systemic gene therapy of cancer.

Dr. Amin Hajitou
Guest Editor

Manuscript Submission Information

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Keywords

  • gene therapy
  • cancer
  • metastasis
  • systemic targeting
  • vector development
  • tumor angiogenesis
  • viral vectors
  • no-viral vectors

Published Papers (3 papers)

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Review

27 pages, 685 KiB  
Review
Genetic Therapy and Molecular Targeted Therapy in Oncology: Safety, Pharmacovigilance, and Perspectives for Research and Clinical Practice
by Sabrina Orzetti, Federica Tommasi, Antonella Bertola, Giorgia Bortolin, Elisabetta Caccin, Sara Cecco, Emanuela Ferrarin, Elisa Giacomin and Paolo Baldo
Int. J. Mol. Sci. 2022, 23(6), 3012; https://doi.org/10.3390/ijms23063012 - 10 Mar 2022
Cited by 5 | Viewed by 2910
Abstract
The impressive advances in the knowledge of biomarkers and molecular targets has enabled significant progress in drug therapy for crucial diseases such as cancer. Specific areas of pharmacology have contributed to these therapeutic outcomes—mainly targeted therapy, immunomodulatory therapy, and gene therapy. This review [...] Read more.
The impressive advances in the knowledge of biomarkers and molecular targets has enabled significant progress in drug therapy for crucial diseases such as cancer. Specific areas of pharmacology have contributed to these therapeutic outcomes—mainly targeted therapy, immunomodulatory therapy, and gene therapy. This review focuses on the pharmacological profiles of these therapeutic classes and intends, on the one hand, to provide a systematic definition and, on the other, to highlight some aspects related to pharmacovigilance, namely the monitoring of safety and the identification of potential toxicities and adverse drug reactions. Although clinicians often consider pharmacovigilance a non-priority area, it highlights the risk/benefit ratio, an essential factor, especially for these advanced therapies, which represent the most innovative and promising horizon in oncology. Full article
(This article belongs to the Special Issue Targeted Gene Therapy of Cancer)
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18 pages, 1130 KiB  
Review
Gene Therapy Targeting p53 and KRAS for Colorectal Cancer Treatment: A Myth or the Way Forward?
by Hidayati Husainy Hasbullah and Marahaini Musa
Int. J. Mol. Sci. 2021, 22(21), 11941; https://doi.org/10.3390/ijms222111941 - 03 Nov 2021
Cited by 24 | Viewed by 7014
Abstract
Colorectal cancer (CRC) is the third most commonly diagnosed malignancy worldwide and is responsible as one of the main causes of mortality in both men and women. Despite massive efforts to raise public awareness on early screening and significant advancements in the treatment [...] Read more.
Colorectal cancer (CRC) is the third most commonly diagnosed malignancy worldwide and is responsible as one of the main causes of mortality in both men and women. Despite massive efforts to raise public awareness on early screening and significant advancements in the treatment for CRC, the majority of cases are still being diagnosed at the advanced stage. This contributes to low survivability due to this cancer. CRC patients present various genetic changes and epigenetic modifications. The most common genetic alterations associated with CRC are p53 and KRAS mutations. Gene therapy targeting defect genes such as TP53 (tumor suppressor gene encodes for p53) and KRAS (oncogene) in CRC potentially serves as an alternative treatment avenue for the disease in addition to the standard therapy. For the last decade, significant developments have been seen in gene therapy for translational purposes in treating various cancers. This includes the development of vectors as delivery vehicles. Despite the optimism revolving around targeted gene therapy for cancer treatment, it also has various limitations, such as a lack of availability of related technology, high cost of the involved procedures, and ethical issues. This article will provide a review on the potentials and challenges of gene therapy targeting p53 and KRAS for the treatment of CRC. Full article
(This article belongs to the Special Issue Targeted Gene Therapy of Cancer)
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14 pages, 609 KiB  
Review
Applications of Ultrasound-Mediated Drug Delivery and Gene Therapy
by Juliana Sitta and Candace M. Howard
Int. J. Mol. Sci. 2021, 22(21), 11491; https://doi.org/10.3390/ijms222111491 - 25 Oct 2021
Cited by 31 | Viewed by 3557
Abstract
Gene therapy has continuously evolved throughout the years since its first proposal to develop more specific and effective transfection, capable of treating a myriad of health conditions. Viral vectors are some of the most common and most efficient vehicles for gene transfer. However, [...] Read more.
Gene therapy has continuously evolved throughout the years since its first proposal to develop more specific and effective transfection, capable of treating a myriad of health conditions. Viral vectors are some of the most common and most efficient vehicles for gene transfer. However, the safe and effective delivery of gene therapy remains a major obstacle. Ultrasound contrast agents in the form of microbubbles have provided a unique solution to fulfill the need to shield the vectors from the host immune system and the need for site specific targeted therapy. Since the discovery of the biophysical and biological effects of microbubble sonification, multiple developments have been made to enhance its applicability in targeted drug delivery. The concurrent development of viral vectors and recent research on dual vector strategies have shown promising results. This review will explore the mechanisms and recent advancements in the knowledge of ultrasound-mediated microbubbles in targeting gene and drug therapy. Full article
(This article belongs to the Special Issue Targeted Gene Therapy of Cancer)
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