In a single-patient-derived PIK3CA H1047R colorectal CSC xenograft model, PF-04691502 at 10 mg/kg orally once daily for 14 days inhibited growth versus vehicle. Day-14 tumor volumes were 360±35 versus 1252±71 mm³ (mean ± SEM; n=8/group; reported P<0.01), with reduced tumor AKT Ser473 phosphorylation and unchanged ERK phosphorylation. [1]
Across six ovarian cancer xenograft models, oral PF-04691502 at 10 mg/kg/day on days 0–4, 7–11, 14–18 and 21–25 produced predominantly tumor growth stasis. Some models initially decreased in volume, but tumors regrew after dosing stopped, limiting interpretation as durable tumor control. [3]
Colorectal CSC-derived xenograft efficacy and tumor signaling
Animal study · Single-patient-derived colorectal CSC xenografts in SCID-bg mice; PIK3CA H1047R. [1]
Daily oral PF-04691502 inhibited tumor growth relative to vehicle and reduced tumor pAKT. The experiment did not demonstrate tumor eradication or a safety margin in normal stem cells.
Conditions shared by the study groups
- Route
- Oral (PO)
- Frequency
- Once daily
- Treatment course
- 14 days
- Vehicle
- 0.5% methylcellulose in water
- PF-04691502 monotherapy
- Model: SCID-bg mice bearing PIK3CA H1047R colorectal CSC-derived xenografts; n=8 per treatment/control group.
- Reported limits: Tumor sampling time relative to final dose not specified in the adopted methods/caption. Methods mention three randomized groups but identify only the two plotted arms; third group is unexplained.
Methods and source locations
Compound reported in the paper: PF-04691502; Compound label in the paper: 502
Model-specific research findings for PF-04691502; no claim that the current A11024 lot was tested.
Materials and Methods: In vivo Antitumor Efficacy Evaluation, Western Blot Analysis; Results: Tumor Growth Inhibition and Reduction of pAKT; Figure 5B-E and caption
Tumor volume at Day 14: Serial tumor volume; Figure 5B caption specifies two-way ANOVA (*P≤0.05; **P≤0.001). Values and P<0.01 are taken from Results, not inferred from the curve. — Materials and Methods: In vivo Antitumor Efficacy Evaluation, Western Blot Analysis; Results: Tumor Growth Inhibition and Reduction of pAKT; Figure 5B-E and caption
Tumor pAKT Ser473 and pERK Thr202/Thr204: Western blot with α-tubulin loading control. No exact percent decrease inferred. — Materials and Methods: In vivo Antitumor Efficacy Evaluation, Western Blot Analysis; Results: Tumor Growth Inhibition and Reduction of pAKT; Figure 5B-E and caption
PF-04691502 monotherapy · Materials and Methods: In vivo Antitumor Efficacy Evaluation, Western Blot Analysis; Results: Tumor Growth Inhibition and Reduction of pAKT; Figure 5B-E and caption
Ovarian xenograft growth response and regrowth
Animal study · Six patient-derived ovarian cancer xenografts in adult female CD-1 nude mice. [3]
PF-04691502 produced predominantly tumor growth stasis across the panel. Initial shrinkage in some models converted to stasis, and growth resumed after treatment stopped. Gedatolisib was a separate comparator, not a combination treatment.
Conditions shared by the study groups
- Route
- Oral gavage
- Frequency
- Days 0–4, 7–11, 14–18 and 21–25
- Treatment course
- Four weeks of scheduled treatment, followed by off-treatment observation.
- Vehicle
- 0.5% carboxymethylcellulose in sterile distilled water
- PF-04691502 across six ovarian xenograft models
- Model: Adult female CD-1 nude mice bearing HOX552, OV1002, HOX516, HOX299, HOX424 or HOX493 xenografts; minimum 6 mice/group and at least 8 tumors/group.
- Reported limits: Exact per-model mouse and tumor counts are not given in the read main text. Two tumors per mouse can be present; tumors are not independent animals. Randomization/blinding not specified in the read growth-study methods.
Methods and source locations
Compound reported in the paper: PF-04691502
Model-specific research findings for PF-04691502; no claim that the current A11024 lot was tested.
Results: Assessment of the antitumour activity of Gedatolisib and PF-04691502 against a panel of xenograft models; Figure 1 and caption; Methods: Xenograft studies; Discussion
Relative tumor growth during treatment and after discontinuation: Calipers; volume = π/6 × length × width². No exact curve values inferred. — Results: Assessment of the antitumour activity of Gedatolisib and PF-04691502 against a panel of xenograft models; Figure 1 and caption; Methods: Xenograft studies; Discussion
PF-04691502 across six ovarian xenograft models · Results: Assessment of the antitumour activity of Gedatolisib and PF-04691502 against a panel of xenograft models; Figure 1 and caption; Methods: Xenograft studies; Discussion
