Novel Agents Aiming at Specific Molecular Targets Increase Chemosensitivity and Overcome Chemoresistance in Hematopoietic Malignancies

Simone      Boehrer; Daniel      Nowak; Dieter      Hoelzer; Paris   S.   Mitrou; Kai   U.   Chow

Abstract

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.

Keywords: Rituximab, Campath-1H, Imatinib, Monoclonal antibodies, HDAC-Inhibitors, Thalidomide, Nuclide / Toxinconjugated Antibodies, Arsenic Trioxide, Proteasome inhibitors, Antisense Oligonucleotide-Bcl-2