title: Pharmacodynamic considerations of small molecule targeted therapy for treating B-cell malignancies in the elderly.
abstract: BACKGROUND
  Small molecule inhibitors are currently in various stages of preclinical and clinical trials and are expected to revolutionize the treatment of many neoplastic diseases, including B-cell lymphoid malignancies.
  
  
  METHODS
  This article reviews the chemical structure, mechanisms of action, pharmacodynamic and pharmacokinetic properties, as well as clinical applications of small molecules in the treatment of elderly patients with B-cell hematological malignancies. Bibliographic research covering mainly the period from 2010 until February 2015 was conducted on the MEDLINE database for articles in English. Proceedings of the American Society of Hematology, European Hematology Association and American Society of Clinical Oncology conferences held during the last 5 years were also included.
  
  
  CONCLUSIONS
  In the last few years, several preclinical and clinical trials have evaluated many small weight organic molecules which downregulate B-cell receptor (BCR) signaling and act via inhibition of either BCR-associated kinases or cyclin-dependent kinases, or which are antagonists of members of the B-cell lymphoma 2 protein family. Pharmacokinetic profiles of these agents as well as dosage used and adverse events in patients with lymphoid malignancies have been established. Some of these inhibitors satisfy therapeutic modalities as suitable for the elderly patients, including those with chronic lymphocytic leukemia and non-Hodgkin's lymphoma.
authors.affiliation: a 1 Medical University of Lodz, Department of Hematology , Ciolkowskiego 2, Lodz, 93-510, Poland +48 42 689 5191 ; +48 42 689 5192 ; robaktad@csk.umed.lodz.pl.
authors.forename: Anna
authors.initials: A
authors.lastname: Korycka-Wołowiec
authors.forename: Dariusz
authors.initials: D
authors.lastname: Wołowiec
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Robak
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D015195:Drug Design; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000188:drug therapy* / Q000473:pathology; D058990:Molecular Targeted Therapy; D011947:Receptors, Antigen, B-Cell / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D011947:Receptors, Antigen, B-Cell
keywords: B-cell malignancies; clinical efficacy; dinaciclib; fostamatinib; ibrutinib; idelalisib; navitoclax; pharmacokinetics; small molecules; venetoclax