TCRT August 2005
No. 4 (p 311-454)
Targeted Drug Delivery for Cancer
Guest Editor: K. K. Jain M.D., FRACS, FFPM Editorial: Targeted Drug Delivery for Cancer (p. 311-314)
Cancer drug delivery is no longer simply wrapping the drug in new formulations for different routes of delivery. Knowledge and experience from other technologies such as nanotechnology, advanced polymer chemistry, and electronic engineering, are being brought together in developing novel methods of drug delivery. Advances in our knowledge of molecular biology of cancer and pathways involved in malignant transformation of cells are revolutionizing the approach to cancer treatment with a focus is on targeted cancer therapy. The newer approaches to cancer treatment not only supplement the conventional chemotherapy and radiotherapy but also aim to prevent damage to the normal tissues and overcome drug resistance. Innovative methods of cancer treatment require new concepts of drug delivery in cancer.
K. K. Jain M.D.
Cancer Gene Therapy
Research and clinical trials in cancer patient is the largest segment of gene therapy activities currently. Yamamoto and Curiel provide a comprehensive review of various techniques and point out the obstacles as well (2). The importance of angiogenesis in growth progression of cancer is well recognized and is the basis of antiangiogenic therapies. Gene therapy is one of important methods of delivering antiangiogenesis agents with the potential of sustained expression. Dickson et al. have reviewed various methods of antiangiogenic gene therapies (3). The article by Robson et al. focuses on the use of gene therapy strategies in combination with radiotherapy, including the use of radiation-sensitive promoters to control the timing and location of gene expression specifically within tumors (4). Gene therapy enhances the effectiveness of radiotherapy with limitations on dose, which falls short of destroying the cancer. The authors also show how radioprotective gene therapy, using transgenes coding for anti-oxidants that can ameliorate the effects of radiation-induced reactive oxygen species, is used to spare normal tissues.
Targeted Drug Delivery
The current focus in development of cancer therapies is on targeted drug delivery to provide therapeutic concentrations of anticancer agents at the site of action and spare the normal tissues. Vasir and Labhasetwar present an overview of the problems related to targeted drug delivery in cancer, and to provide an insight into the issues related to the development of targeted drug delivery systems for cancer (5). The authors have described several technologies for targeted drug delivery in cancer and suggest that combination of some of these approaches may provide solutions to some of the problems encountered.
Drug Delivery Using Monoclonal Antibodies
Monoclonal antibodies (MAbs) are used both for diagnosis and therapy in cancer. Several MAbs are in the market for cancer therapy. MAbs are being paired with powerful toxins and radiopharmaceuticals to create specific agents that seek out cancer cells and kill them. Govindhan et al. describe targeted cancer therapy with radiolabeled and drug/toxin-conjugated MAbs and methods of producing these conjugates (6). The clinical potential of these therapies in hematological malignancies is promising. For the treatment of solid tumors, the authors suggest application of combination therapies and use in residual disease rather than in bulky tumors. Bethge and Sandmaier have shown how radioimmunotherapy combines the advantages of targeted radiation therapy and specific immunotherapy using MAbs to target tumor cells (7). Radiolabeled MAbs enable the reduction of toxicity of conventional strategies of radiation therapy and enhance the efficacy of MAbs. The authors provide an overview of available radionuclides and radioimmunoconjugates and discusses clinical results in hematological malignancies.
Nanotechnology-based Drug Delivery
Nanobiotechnologies have been applied to improve drug delivery and to overcome some of the problems of drug delivery in cancer. The article by Jain describes various nanoparticles, nanoencapsulation for targeted delivery to tumors of various organs and combination of these with other methods of treatment of cancer such as radiotherapy (8). Nanoparticles are also used for gene therapy for cancer. The author points out how nanotechnology-based diagnostics can be combined with therapeutics, which will be important for the personalized management of cancer.
Drug Delivery in Brain Tumors
One of the major limitation in treatment of brain tumors is lack of a suitable method for delivery of therapeutics to the site of the lesion. The challenge for systemic therapy is to cross the blood-brain and brain-tumor barriers for achieving high drug concentrations within the tumor bed. There are at least a dozen categories of methods under investigation for drug delivery to brain tumors. Lesniak has reviewed important advances in drug delivery for brain cancer (9). The only currently approved therapy is based on local controlled delivery of chemotherapeutic agents by a biodegradable polymer. The author also describes examples of promising non-polymer based drug delivery methods.
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