Books > Medicine > Clinical & internal medicine > Diseases & disorders > Oncology
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Targeted Drug Strategies for Cancer and Inflammation (Paperback, 2011 ed.)
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Targeted Drug Strategies for Cancer and Inflammation (Paperback, 2011 ed.)
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Folate pathways are essential in metabolism and macromolecule
synthesis. Antifolate drugs that are largely transported via a high
capacity folate transporter (i.e. the reduced-folate carrier) and
inhibit folate-dependent enzymes include the dihydrofolate
reductase inhibitor, methotrexate, and the thymidylate synthase
inhibitors, raltitrexed and pemetrexed. Major advances in folate
research made within the last decade include (i) the approval of
pemetrexed for the treatment of lung cancer and mesothelioma, and
(ii) the demonstration that cell membrane-anchored folate receptors
(FR) are exploitable for cancer and inflammatory disease
management. FRs are not widely distributed in normal tissues,
except on some luminal surfaces; however, they are accessible to
systemically administered agents when expressed on many cancers as
well as on activated macrophages involved in various inflammatory
diseases. High affinity folate-radioisotope conjugates have been
developed for imaging pathogenic FR-positive diseases, including
cancer. Since the FR transports folates via a low capacity but high
affinity endocytic pathway, a variety of FR-targeted antifolate
drugs and folate conjugates bearing a wide range of payloads
(including cytotoxic drugs) are currently being developed which
exploit this property. The FR is also being utilized in
immunotherapy approaches for the treatment of overexpressing
cancers.
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