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Targeted Drug Delivery for Cancer
Editorial: Targeted Drug Delivery for Cancer (p.
311-314)
Abstract
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.
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| There is a vast range of strategies available for drug
delivery in cancer. A classification of these is shown in Table I. |
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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.
References
Jain, K. K. Drug Delivery in Cancer, pp 1-433. Jain Pharmabiotech
Publications, Basel (2005).
Yamamoto, M., Curiel, D. T. Cancer Gene Therapy. TCRT 4, 315-330 (2005).
Dickson, P. V., Nathwani, A. C., Davidoff, A. M. Delivery of Antiangiogenic
Agents for Cancer Gene Therapy. TCRT 4, 331-342 (2005).
Robson, T. 1., Worthington, J., McKeown, S. R., Hirst, D. G. Radiogenic
Therapy: Novel Approaches for Enhancing Tumor Radiosensitivity. TCRT 4,
343-362 (2005).
Vasir, J. K., Labhasetwar, V. Targeted Drug Delivery in Cancer Therapy. TCRT
4, 363-374 (2005).
Govindan, S. V., Griffiths, G. L., Hansen, H. J., et al. Cancer Therapy with
Radiolabeled and Drug/Toxin-conjugated Antibodies. TCRT 4, 375-392 (2005).
Bethge, W. A., Sandmaier, B. M. Targeted Cancer Therapy Using Radiolabeled
Monoclonal Antibodies. TCRT 4, 393-406 (2005).
Jain, K. K. Nanotechnology-based Drug Delivery for Cancer. TCRT 4, 407-416
(2005).
Lesniak, M. S. Novel Advances in Drug Delivery to Brain Cancer. TCRT 4,
417-428 (2005).
Source: K. K. Jain M.D., FRACS, FFPM
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