cancer

An Introduction to Cancer Gene Therapy

Cancer can be described as a disease where cellular communication has broken down, allowing transformed cells to escape tight regulatory signals and to replicate autonomously and continously, ultimately invading and interfering with the functions of normal tissues. Under physiological conditions cells communicate with one another by activating receptors at the cell surface, which convey the signal through pathways of proteins located in the cytoplasm and subsequently through networks of transcription factors in the nucleus with control the expression of genes that mediate the cell's response. In this article we briefly describe the gene therapy approaches that have been adopted in an effort to treat cancer.

Typically, cancer develops as a result of aberrant growth factor signalling, where a pathway that instructs a cell to grow and divide becomes constitutively active. This arises through mutations in a growth factor receptor, or through mutations in the components of cell signalling pathways. (Collectively, genes that encode for mutated cellular proteins involved in promoting cell growth are termed oncogenes). Threrefore, in order to effectively treat a cancer, it is essential that all cells that carry a mutated oncogene, are destroyed, otherwise the cancer will continue to grow and spread.

Mice cured of lung cancer with gene therapy

LONDON — Mice with up to 200 tumours have been completely cured of lung cancer using a “gene therapy” technique, scientists claim. By blocking production of a protein which drives the development of tumours, researchers were able to eliminate the tumours without any evidence of adverse sideeffects, the Daily Telegraph reported. The study found that the treatment was effective even after several rounds of therapy suggesting that the mice did not become resistant to it – a major problem for cancer doctors.

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Researchers, FDA Evaluating Experimental Gene Therapy Procedures for Mesothelioma Treatment

According to the BBC (November 2012), geneticists, scientists and the entire medical profession are applauding the European Commission for bringing ‘a new era to medicine in the Western world’ by approving Glycera, a Dutch gene therapy medicine for treating a rare, inherited disorder known as LPLD. While gene therapy has been gaining momentum for years since French scientists first used it in 2000 to treat a rare immune disorder called SCID, Glycera’s approval may be the breakthrough needed to move gene therapy to sufferers of other rare diseases such as mesothelioma.

Aptamer Targeting of Osteopontin in Cancer Metastasis

In recent years a novel crop of therapies called aptamers have been derived that take advantage of small segment nucleotides that tightly bind cell surface proteins. This interaction at the extracellular level impedes the normal cascade of the receptor protein, blunting or arresting the usual chain of intracellular events. In contrast to antibody directed therapies, aptamers are able to function at very low concentrations. In addition to the robust binding capability to target cell surface proteins (as described by the dissociation constant), added benefits of aptamer therapy include exquisite target specificity and a lack of immunogenicity (1, 2).

Targeted Prostate Cancer Gene Therapy

Prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer deaths in American males today. Novel and effective treatment such as gene therapy is greatly desired. Gene therapy is the direct transfer of DNA into patients’ diseased cells for the purpose of therapy. Viral based gene therapy is to use a genetically-modified, replication defective or so-called cold virus as the gene transfer vehicle. In contrast, nonviral gene therapy is to deliver DNA by nonviral methods. At the current stage, viral gene therapy in general has a much higher gene transfer efficiency in vivo compared to nonviral gene therapy. The early viral-based gene therapy uses tissue-nonspecific promoters, which causes unintended toxicity to other normal tissues. In this mini-review, we will focus on discussion of strategy using transcriptionally-regulated gene therapy strategy for prostate cancer treatment.

First 'nano' treatments to target cancer cells

Cancer Research UK scientists have for the first time developed a treatment that transports 'tumour busting' genes selectively to cancer cells, according to a study published online in Cancer Research*. Using nanotechnology, the researchers were able to package anti-cancer genes in very small particles that directed the treatment selectively to tumours in mice so that it was only taken up by cancer cells, leaving healthy cells unharmed. Once taken up by cancer cells, the genes enclosed in the nanoparticles force the cell to produce proteins that can kill the cancer.

Gene Therapy for Malignant Pleural Mesothelioma

Mesothelioma is relatively rare in frequency but is one of the intractable cancers linked with asbestos exposure. The patient numbers will increase in near future and current clinical outcomes with conventional treatment modalities are not satisfactory. Gene therapy is a possible therapeutic strategy because of easy accessibility of a vector system into the intrapleural cavity. Several preclinical studies demonstrated that the gene medicine produced anti-tumor effects, suggesting the clinical feasibility. In this review, we summarized the current status of clinical trials targeting mesothelioma.

p53 Gene Therapy

Replication-defective adenoviruses are widely used as gene transfer vectors to deliver cytostatic or tumour suppressor genes into a variety of cancers, yielding some of the most promising results in the clinic. Indeed, the most successful adenoviral vectors used to date are those that are designed to deliver p53 into tumours. Tumor cells have lost the function of p53 because of mutations in the DNA-binding region of the molecule, a feature that is present in over 50% of all human malignancies. A number of studies have demonstrated that transfer of wild type (wt) p53 gene is able to suppress tumor cell proliferation. Moreover, platinum-based chemotherapy enhances mutations in the p53 in the heterogenous cell population; transfer of the wild type p53 gene enhanced the sensitivity of chemoresistant cells to cisplatin and cisplatin-induced apoptosis (Kigawa et al, 2002). This has led to a significant amount of clinical trials where wt p53 has been re-introduced to tumour cells by the use of first-generation adenoviral vectors.