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. Author manuscript; available in PMC: 2015 Jul 14.
Published in final edited form as: Cancer Cell. 2014 Jul 4;26(1):136–149. doi: 10.1016/j.ccr.2014.05.020

Figure 6. Correlation between post-treatment pRB levels and sensitivity to single-agent PI3Ki in vitro and in patient biopsy specimens.

Figure 6

A) 5 sensitive PIK3CA mutant cell lines (IC50≤400nM to BYL719) and 5 de novo resistant PIK3CA cell lines (IC50≥800nM to BYL719) were treated with media or with BYL719 1 μM (BYL) for 24 hours, and lysates were probed with the indicated antibodies. The fraction of remaining pRB (relative to actin) was calculated for both the sensitive and resistant lines and a student's t test was performed. *indicates p<0.05 by student's t test.

B) Eight patients enrolled in early clinical trials of BYL719 were classified as responders or nonresponders as previously described (Elkabets et al., 2013) (n=4 in each group). Biopsy specimens were collected within 2 weeks prior to start of treatment and while on treatment. Slides were prepared, stained and scored for pRB (see Supplemental Experimental Procedures). The percentage change relative to pretreatment levels of pRB for both the responders and the nonresponders is depicted. * indicates p<0.05 by students t-test.

C) Representative sections from a tumor that initially responded to BYL719, stained by IHC for pRB 780 in paired biopsies prior to treatment, day 56 of BYL719 (during response), and at progression, with quantitative H-score.

D) Representative sections from a nonresponsive tumor to BYL719, stained by IHC for pRB 780 in paired biopsies prior to treatment and at day 56 of BYL719, with quantitative H-score.

All error bars in this figure represent +/- SEM.

See also Figure S6.