RT Book, Section
A1 Craig, Gedye
A2 Tannock, Ian F.
A2 Hill, Richard P.
A2 Bristow, Robert G.
A2 Harrington, Lea
SR Print(0)
ID 1127472689
T1 Heterogeneity in Cancer: The "Cancer Stem Cell" Hypothesis
T2 The Basic Science of Oncology, 5e
YR 2016
FD 2016
PB McGraw-Hill Education Medical
PP New York, NY
SN 9780071745208
LK accessbiomedicalscience.mhmedical.com/content.aspx?aid=1127472689
RD 2024/04/25
AB Every  patient's  cancer  is  different.  Cancers  arising  from  the  same  organ  have  different  histology  and  metastatic  proclivity,  are  more  or  less  aggressive,  and  have  different  responses  to  therapy.  There  are  many  interdependent  mechanisms  and  dimensions  of  heterogeneity  that  account  for  this  variability  between  cancers.  There  is  also  heterogeneity  within  individual  cancers,  between  stromal  cells  with  a  normal  genome  and  mutated  malignant  cells,  between  differently  mutated  malignant  clones,  between  epigenetically  different  subpopulations  within  clonal  populations,  and  between  cells  within  different  microenvironments  within  the  tumor  (Fig.  13–1;  see  Chap.  12,  Sec.  12.2).  Recognition  of  this  heterogeneity  gives  rise  to  the  intriguing  possibility  that  a  subset  of  cancer  cells  are  resistant  to  treatment,  may  cause  primary  tumor  recurrence  or  seed  distant  metastasis,  and  may  be  identifiable  a  priori.  A  surgeon's  concern  in  ensuring  complete  resection  of  primary  tumors  ("negative  margins")  where  more  invasive  cancer  cells  may  reside,  the  prognostic  relevance  of  circulating  tumor  cells  (see  Chap.  10,  Sec.  10.3.4),  and  the  resistance  of  disseminated  micrometastases  to  adjuvant  chemotherapy  are  phenomena  that  might  be  explained  by  "special"  cells  within  a  cancer,  so-called  cancer  stem  cells,  cells  that  must  be  targeted  to  achieve  long-term  remission  or  cure.  The  cancer  stem  cell  (CSC)  hypothesis  states  that  only  a  minority  of  cancer  cells  has  the  potential  to  (a)  self-renew,  (b)  proliferate  indefinitely,  and  (c)  differentiate  to  give  rise  to  more  differentiated  tumor  cells  (Reya  et  al,  2001).  This  chapter  addresses  the  competing  models  that  attempt  to  account  for  this  epigenetic  heterogeneity,  led  by  the  CSC  hypothesis,  but  first  describes  the  stromal  and  genetic  heterogeneity  of  human  cancers.