To date, none of the approximately 60 anticancer drugs used in conventional chemotherapy exhibits a selective uptake in tumor tissue and generally only a very small fraction of the administered dose reaches the tumor site. If surgery or radiotherapy is not effective, cure rates are in the range of 10% and, as a consequence, 90 % of chemotherapeutic agents are administered in the palliative setting to stabilize the disease or to improve the quality of life.
With such a low rate of drug accumulation in the tumor it is in fact surprising that tumor remissions can be attained; admittedly, these are achieved in the fast-growing tumors where cytostatic agents alone or in combination therapy are most effective in killing the rapidly dividing tumor cells by inhibiting different specific targets of the tumor cell that are responsible for tumor proliferation.
Generally, however, tumor doubling times are slow, the tumor cells are in different stages of their cell cycles, and vascularization in the tumors is heterogeneous with necrotic and hypo hypoxic areas being present that respond poorly to anticancer agents.
Last, but not least, late-stage tumors have mostly formed micro- and macrometastases that are characterized by the multidrug resistance phenotype that includes changes in the cellular target of the respective drug, alterations in enzymatic activation and detoxification mechanisms, defective apoptotic pathways, membrane changes as well as elimination of the drug from the tumor cell through the action of drug efflux pumps.
For treating metastatic cancer, chemotherapy regimens applied alone or in combination with hormones or novel agents such as monoclonal antibodies and signal transduction inhibitors are to date the best option of inhibiting or reducing the size of the primary tumor and/ or metastases. However, treatment is basically palliative and improvement in overall survival through the introduction of novel drugs has generally not been more than a few months.
Anticancer agents have steep dose-response curves, which has the consequence that a critical toxic concentration of the drug must be exposed to the tumor cell for a sufficient time to induce cell killing. The dilemma of conventional chemotherapy as well as with low-molecular-weight targeted therapeutics is that due to an unfavorable biodistribution and a lack of accumulation in tumor tissue, they exhibit poor therapeutic indices and tumor remissions are often not achieved.
It is here where the potential of drug delivery in oncology resides. Any means of transporting and delivering anticancer drugs in higher concentrations to the tumor over a long period of time whilst sparing healthy tissue is a step to a more effective cancer chemotherapy. This goal has been pursued for approximately 60 years, and has en compassed encapsulating or conjugating drugs with vitamins, lipids, peptides, oligonucleotides, antibodies, serum proteins, synthetic or natural polymers, liposomes, or protein- or polymer-based nano- or microparticles.
Aided by the advent of sophisticated diagnostic tumor imaging and analytical tools that have enabled a far more precise understanding of the biochemical and physiological characteristics of tumor cells and tissue, as well as the expression of tumor-associated receptors and antigens, scientists have more opportunities than ever for designing and validating new drug delivery systems. During this process, we are also learning that similar to the translation of targeted therapies into the clinic, drug delivery systems are probably most effective in the form of a personalized medicine and in combination with established chemotherapeutic regimens.
Different anti-drug delivery systems realized to date The products that have reached the clinical setting or have obtained market approval The challenges that lie ahead in translational research in the area of cancer drug delivery. Cancer, also called malignancy, is characterized by an abnormal growth of cells. There are more than 100 types of cancer, including breast cancer, skin cancer, lung cancer, colon cancer, prostate cancer, and lymphoma. Cancer symptoms vary widely based on the type of cancer. Cancer treatment includes chemotherapy, radiation, and surgery.
Cancer diagnosis begins with a thorough physical exam and a complete medical history. Laboratory studies of blood, urine, and stool can detect abnormalities that may indicate cancer. When a tumor is suspected, imaging tests such as X-rays, computed tomography (CT), magnetic resonance imaging (MRI), ultrasound, and fiber-optic endoscopy examinations help doctors determine the cancer’s location and size. To confirm the cancer diagnosis, a biopsy is performed in which a tissue sample is surgically removed from the suspected tumor and studied under a microscope to check for cancer cells.
This is mandatory to diagnose cancer. The incidence of cancer and cancer types are influenced by many factors such as age, sex, race, local environmental factors, diet, and genetics. Consequently, the incidence of cancer and cancer types vary depending on these variable factors. For example, the World Health Organization (WHO) provides the following general information about cancer worldwide: * Cancer is a leading cause of death worldwide. It accounted for 7.
4 million deaths (around 13% of all deaths) in 2004 (statistics published in 2009). * Lung, stomach, liver, colon, and breast cancer cause the most cancer deaths each year. * Deaths from cancer worldwide are projected to continue rising, with an estimated 12 million deaths in 2030. Different areas of the world may have cancers that are either more or less predominant then those found in the U. S. One example is that stomach cancer is often found in Japan, while it is rarely found in the U. S.