TY - JOUR

T1 - Breast cancer stem cells

T2 - A moving target for cancer nanomedicine

AU - Mollenhauer, Jan

AU - Knoop, Ann

AU - Bak, Martin

AU - Laenkholm, Anne Vibeke

AU - Thomassen, Mads

AU - Kruse, Torben A.

AU - Hoilund-Carlsen, Poul Flemming

PY - 2012/12

Y1 - 2012/12

N2 - The identifi cation of so-called cancer stem cells (CSCs) has sustainably changed our views on cancer by adding hierarchical principles, where tumor cells emerge from a founder population similar to steady-state regenerative processes in normal tissues. The rare founder population of CSCs is thought to be responsible for the recurrence of treatment-resistant tumors and metastatic spread and thus has been declared as the number one target for the next generation of anti-cancer drugs. Here, we will review the state of the art in research on breast cancer stem cells (BCSCs), for which a huge amount of data has accumulated in the past few years. Initial studies have suggested that the CD44 + /CD24- profi le and epithelial-tomesenchymal transition (EMT) are associated with BCSCs, which has resulted in the recent identifi cation of fi rst compounds with BCSC-eliminating properties. In this early phase, however, it remains mostly unclear, to which extent these new compounds may exert toxicity to normal stem cells, since a substantial part targets molecular pathways critical for normal stem cell function. Moreover, these new drugs often require combination with conventional chemotherapeutics potentially posing new challenges to nanomedicine in circumventing toxicity and enabling targeted delivery. Most recent data further suggests that normal breast cancer cells might be able to re-create BCSCs and that additional, yet undiscovered kinds of BCSCs may exist. This points to future escape mechanisms. As a consequence, another broad future fi eld of nanomedicine might be fi nding new drugs via systematic screening approaches. Collectively, this area provides ample possibilities for both traditional and novel nanomedical approaches.

AB - The identifi cation of so-called cancer stem cells (CSCs) has sustainably changed our views on cancer by adding hierarchical principles, where tumor cells emerge from a founder population similar to steady-state regenerative processes in normal tissues. The rare founder population of CSCs is thought to be responsible for the recurrence of treatment-resistant tumors and metastatic spread and thus has been declared as the number one target for the next generation of anti-cancer drugs. Here, we will review the state of the art in research on breast cancer stem cells (BCSCs), for which a huge amount of data has accumulated in the past few years. Initial studies have suggested that the CD44 + /CD24- profi le and epithelial-tomesenchymal transition (EMT) are associated with BCSCs, which has resulted in the recent identifi cation of fi rst compounds with BCSC-eliminating properties. In this early phase, however, it remains mostly unclear, to which extent these new compounds may exert toxicity to normal stem cells, since a substantial part targets molecular pathways critical for normal stem cell function. Moreover, these new drugs often require combination with conventional chemotherapeutics potentially posing new challenges to nanomedicine in circumventing toxicity and enabling targeted delivery. Most recent data further suggests that normal breast cancer cells might be able to re-create BCSCs and that additional, yet undiscovered kinds of BCSCs may exist. This points to future escape mechanisms. As a consequence, another broad future fi eld of nanomedicine might be fi nding new drugs via systematic screening approaches. Collectively, this area provides ample possibilities for both traditional and novel nanomedical approaches.

KW - Breast cancer stem cells

KW - Cancer nanomedicine

KW - Cancer stem cells

KW - Cancer treatment

UR - http://www.scopus.com/inward/record.url?scp=84882428464&partnerID=8YFLogxK

U2 - 10.1515/ejnm-2012-0006

DO - 10.1515/ejnm-2012-0006

M3 - Review

AN - SCOPUS:84882428464

VL - 4

SP - 59

EP - 72

JO - European Journal of Nanomedicine

JF - European Journal of Nanomedicine

SN - 1662-5986

IS - 2-4

ER -