Novel approaches for targeted cancer therapy.
The clinical use of chemotherapeutic agents against malignant tumors is successful in many cases but suffers from major drawbacks. One drawback is lack of selectivity, which leads to severe side effects and limited efficacy; and another is the emergence/selection of drug-resistance. To limit non-specific toxicity and to improve the efficiency of cancer therapy, "tumor markers", which are proteins generally overexpressed on the surface of tumor cells, can be selectively targeted. Growth factor receptors are one of the most extensively studied tumor markers. The implication of growth factor receptors in the pathogenesis and evolution of cancer has clearly been established and therefore, provides a rationale for therapeutic intervention. The targeting of cytotoxic substances to tumor markers with "magic bullets" is an old idea that raised high expectations but also disappointment. Over the past decade, newly gained understanding of mechanisms for targeted therapy have brought new hopes. Pharmacological agents that selectively target and block the action of growth factors and their receptors have been attempted, such as monoclonal antibodies (mAbs) (whole molecule or fragments), bispecific antibodies, mAbs conjugated to drugs, toxins or radioisotopes, small peptidic and peptidomimetic molecules in free form or conjugated to drugs, anti-sense oligonucleotides, immunoliposomes-encapsulated drugs, and small molecule inhibitors. This review will focus on current developments of selective targeting and bypassing drug resistance in the management of growth factor receptor-overexpressing tumors.
Guillemard
Veronique
V
Departments of Pharmacology and Therapeutics, Oncology, and the Cancer Center, McGill University, Montreal, Quebec, Canada. uri@pharma.mcgill.ca
Saragovi
H Uri
HU
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D008024:Ligands; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D008024:Ligands; D017978:Receptors, Growth Factor