Cancers affecting mankind
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...
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