Novel agents aiming at specific molecular targets increase chemosensitivity and overcome chemoresistance in hematopoietic malignancies.
In hematologic neoplasias primary or secondary resistance of malignant cells towards the applied treatment presents the major clinical obstacle in the induction of remission and definite cure. Evaluation of the underlying molecular mechanisms determining response or resistance not only enables the clinician to define prognostic markers, but moreover facilitates the design of molecularly targeted agents potentially reversing the causative lesion. Deregulation of apoptosis is considered to contribute to the emergence and propagation of the malignant clone, and several molecular alterations hindering programmed cell death and thus leading to chemoresistance have been defined. While reviewing these molecular alterations this article moreover focuses on the impact of new therapeutic agents, which specifically exploit the knowledge of the molecular characteristics of malignant hematopoetic cells.
Boehrer
Simone
S
Johann Wolfgang Goethe University Hospital, Department of Internal Medicine II, Hematology/Oncology, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
Nowak
Daniel
D
Hoelzer
Dieter
D
Mitrou
Paris S
PS
Chow
Kai Uwe
KU
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000627:therapeutic use; D001549:Benzamides; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D019337:Hematologic Neoplasms / Q000188:drug therapy*; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D000068877:Imatinib Mesylate; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use; D010087:Oxides / Q000627:therapeutic use; D010879:Piperazines / Q000627:therapeutic use; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects; D011743:Pyrimidines / Q000627:therapeutic use; D000069283:Rituximab; D013792:Thalidomide / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D001152:Arsenicals; D001549:Benzamides; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D016376:Oligonucleotides, Antisense; D010087:Oxides; D010879:Piperazines; D011743:Pyrimidines; D000069283:Rituximab; D013792:Thalidomide; D000068877:Imatinib Mesylate; D046988:Proteasome Endopeptidase Complex; D000077237:Arsenic Trioxide