The future of targeted therapy: combining novel agents.
The anti-HER2 monoclonal antibody Herceptin demonstrates significant clinical benefits in patients with HER2-positive metastatic breast cancer (MBC). However, the combination of Herceptin plus anthracyclines, although efficacious, demonstrated a higher than expected incidence of cardiotoxicity. Therefore, studies are currently investigating Herceptin in combination with alternative anthracyclines, such as epirubicin and liposomal doxorubicin. Investigators are also beginning to examine the potential of Herceptin plus hormonal therapy, a combination that will delay the need to use cytotoxic chemotherapy. Furthermore, a plethora of novel agents have been developed that target the processes of tumorigenesis, including HER1 tyrosine-kinase inhibitors, farnesyl-transferase inhibitors, and cyclooxygenase 2 (COX2) inhibitors. Preclinical data demonstrate that the combination of Herceptin with these agents can produce at least additive effects and therefore a rationale exists to investigate these regimens in the clinical setting. As a result of the targeted nature of these agents, it is anticipated that such strategies will have favorable safety profiles. It is possible that through the development and use of biological anticancer agents, such as Herceptin, future anticancer regimens may be specifically tailored to each patient based on their molecular characteristics.
Gianni
Luca
L
Division of Medical Oncology, Istituto Nazionale Tumori, Via Venezian 1, I-20133 Milan, Italy. gianni@institutotumori.mi.it
D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D002455:Cell Division / Q000187:drug effects; D051546:Cyclooxygenase 2; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008565:Membrane Proteins; D008954:Models, Biological; D011451:Prostaglandin-Endoperoxide Synthases; D013629:Tamoxifen / Q000008:administration & dosage; D000068878:Trastuzumab
D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007527:Isoenzymes; D008565:Membrane Proteins; D013629:Tamoxifen; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D066246:ErbB Receptors; D000068878:Trastuzumab