TY  - CHAP
M1  - Book, Section
TI  - Discovery and Evaluation of Anticancer Drugs
A1  - Aung, Kyaw Lwin
A1  - Cescon, David W.
A1  - Schimmer, Aaron D.
A2  - Harrington, Lea A.
A2  - Tannock, Ian F.
A2  - Hill, Richard P.
A2  - Cescon, David W.
PY  - 2021
T2  - The Basic Science of Oncology, 6e
AB  - Drug-based  systemic  therapy  is  used  primarily  as  (1)  the  major  treatment  modality  for  a  few  types  of  curable  malignancies,  such  as  Hodgkin  disease  and  other  hematopoietic  cancers,  acute  leukemia  in  children,  and  testicular  cancer  in  men;  (2)  palliative  treatment  for  many  types  of  advanced  cancers;  and  (3)  adjuvant  treatment  before,  during,  or  after  local  treatment  (surgery  and/or  radiotherapy)  with  the  dual  aims  of  both  eradicating  occult  micrometastases  and  of  improving  local  control  of  the  primary  tumor.  Such  treatments  usually  involve  a  combination  of  drugs.  The  most  important  factors  underlying  the  successful  use  of  drugs  in  combination  are  (1)  the  ability  to  combine  drugs  at  close  to  full  tolerated  doses  with  additive  effects  against  tumors  and  less  than  additive  toxicities  to  normal  tissues  and  (2)  the  expectation  that  drug  combinations  will  include  at  least  1  drug  to  which  the  tumor  is  sensitive.  Since  the  first  documented  clinical  use  of  chemotherapy  in  1942,  when  the  alkylating  agent  nitrogen  mustard  was  used  to  obtain  a  brief  clinical  remission  in  a  patient  with  lymphoma,  there  have  been  continuous  efforts  to  develop  new,  effective  anticancer  therapies.  Initially  focused  on  cytotoxic  chemotherapies  (the  pharmacology  of  which  are  described  in  Chap.  18),  the  number  and  range  of  cancer  drugs  has  expanded,  with  more  than  200  drugs  or  biologic  agents  licensed  for  use  in  North  America,  and  many  more  undergoing  clinical  trials.  New  types  of  anticancer  agents  that  have  emerged  include  monoclonal  antibodies  (such  as  trastuzumab,  cetuximab,  bevacizumab,  and  blinatumomab)  that  target  cell  surface  receptors,  and  small  molecules  that  interact  with  various  cell  signaling  or  survival  pathways  (eg,  imatinib,  erlotinib,  afatinib,  venetoclax).  These  newer  “targeted”  agents  (reviewed  in  Chap.  19)  represent  a  substantial  shift  in  emphasis  in  anticancer  drug  therapy.  In  contrast  to  conventional  cytotoxic  agents,  which  usually  target  proliferating  cells  and  interact  with  DNA,  these  target  specific  pathways  that  interfere  with  various  functions  of  the  cell  including  those  that  promote  cell  division  (trastuzumab,  imatinib),  cell  survival,  and  apoptosis  (venetoclax)  or  contribute  to  immune-mediated  cellular  damage  (blinatumomab).  Other  agents,  such  as  those  that  inhibit  angiogenesis  (eg,  bevacizumab;  see  Chap.  11)  act  indirectly  to  inhibit  tumor  growth.  
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/19
UR  - hemonc.mhmedical.com/content.aspx?aid=1179325306
ER  -