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Validating the use of a luciferase labeled breast cancer cell line, MDA435LCC6, as a means to monitor tumor progression and

to assess the therapeutic activit of an established anticancer drug, doceta!el "Dt# alone or in combination $ith the %L& inhibitor, 'L()*6+
Volume 11, Issue 9 Ma ,, *),, -ages .*6 / .3. http://dx.doi.org/10.4161/cbt.11.9.15183 Jessica Kalra, Malathi Anantha, Corinna Warburton, Dawn Waterhouse, Hong Yan, Young !oo Yang, Dita "trut, Mar#am $sool#, Dana Masin an% Marcel &' &all# View a((iliations

A signi(icant issue in %rug e((icac# stu%ies is animal stu%# %esign' Here we h#)othesi*e that when e+aluating new or e,isting thera)eutics (or the treatment o( cancer, the location o( %isease bur%en will in(luence %rug e((icac#' -o stu%# this, .emale /Cr nu%e mice were inoculate% with luci(erase )ositi+e human breast cancer cells 01CC2W- luc3 orthoto)icall# 0o't'3, intra)eritoneall# 0i')'3 or intracar%iacl# 0i'c'3 to create locali*e%, ascites or %isseminate% %isease, res)ecti+el#' -umor %e+elo)ment was monitore% using bioluminescence imaging' Doceta,el 0Dt3 )harmaco4inetics an% %istribution to sites o( tumor growth were %etermine%' Disease )rogression was (ollowe% in animals treate% with Dt alone an% in combination with 51-6728, an Integrin 1in4e% Kinase inhibitor' -umor relate% morbi%it# was most ra)i% when cells were inoculate% i'c', where %isease )rogression was obser+e% in brain, o+aries, a%renal glan%s, an% lungs' Dt )harmaco4inetics were com)arable regar%less o( the mo%el use% 0mean )lasma A9C6 7:hrs :;7'2 ng<ml=hr3, howe+er, Dt le+els were lowest in those tissues %e+elo)ing %isease (ollowing i'c' cell in!ection' -reatment with low %ose Dt 0> mg<4g3 increase% o+erall sur+i+al an% re%uce% tumor cell growth in all three mo%els but the acti+it# was greatest in mice with orthoto)ic tumors' Higher %oses o( Dt 01> mg<4g3 was able to )rolong sur+i+al in animals bearing i')' tumors but not i'c' tumors' A%%ition o( 51-6728 )ro+i%e% no a%%e% bene(it abo+e Dt alone in the %isseminate% mo%el' -hese stu%ies highlight a nee% (or more com)rehensi+e in +i+o e((icac# stu%ies %esigne% to assess multi)le %isease mo%els an% multi)le en%)oints, (ocusing anal#sis o( %rug )arameters on the most chemoresistant %isease'