Molecular target therapy in hematological malignancy: front-runners and prototypes of small molecule and antibody therapy.
Molecular-targeted drugs were first introduced for the treatment of hematological malignancies. Herein, the success stories of small molecule-targeted drugs, such as imatinib for the treatment of chronic myeloid leukemia and the tumor-specific antibody rituximab for the treatment of CD20-positive lymphoma, will be introduced. The introduction of imatinib and rituximab has changed the mortality rates associated with chronic myeloid leukemia and CD20-positive lymphoma, respectively. In particular, the therapeutic outcomes of imatinib treatment have been so good that clinical trials to assess the feasibility of treatment discontinuation after remission are ongoing. Methods for developing new anti-cancer agents have changed, and structure-based chemical compounds are now screened in silico. Second- and third-generation anti-cancer agents have already been successfully identified, and resistance mechanisms have been explained based on the interaction of these chemical structures with their target molecules. In the area of antibody development, the introduction of humanized antibody has been successful, and the use of antibody carriers has resulted in the development of potent second-line antibody drugs. The discovery of new target surface markers is also being reported, and trials for both chimeric and humanized antibodies against these molecules are ongoing. Through these efforts, disease mortality rates have begun to decline. We are facing a brilliant future in which we can strive to eliminate cancer-related mortality.
National Cancer Center Hospital, Hematology Division, Tokyo, Japan. ykkobaya@ncc.go.jp
Yukio
Y
Kobayashi
D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D018951:Antigens, CD20; D001549:Benzamides; D015415:Biomarkers; D015507:Drugs, Investigational; D019337:Hematologic Neoplasms / Q000188:drug therapy*; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy; D008224:Lymphoma, Follicular / Q000188:drug therapy; D058990:Molecular Targeted Therapy; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; D001549:Benzamides; D015415:Biomarkers; D015507:Drugs, Investigational; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate