Establishment of 12 PDX from BRAF inhibitor–progressed patients.

Slides:

Advertisements

Similar presentations

Dose-escalation patient response.

Advertisements

Volume 18, Issue 8, Pages (February 2017)

Combined RAF and EGFR inhibition leads to improved in vivo efficacy in BRAF-mutant colorectal cancer. Combined RAF and EGFR inhibition leads to improved.

Genetic alterations in the PI3K–PTEN–AKT pathway detected during disease progression and their functional impacts. Genetic alterations in the PI3K–PTEN–AKT.

Supplementary Figure 2 Secondary transplanted brain tumors from PASC1 express human GH. Immuno-fluorescence staining of brain sections from mice implanted.

Cells from TUM622 acini are capable of self-renewal and recapitulate the intratumoral heterogeneity observed in the PDX model and original human tumor.

Sunitinib plus rMVA–CEA–TRICOM vaccine decreased tumor burden and increased intratumoral infiltration of T lymphocytes in the MC38-CEA colon carcinoma.

H31m1-PDL1 cells form progressively growing tumors in WT mice.

JNK signaling mediates mammary tumor growth and metastasis to lungs

The EGF receptor confers BRAF inhibitor resistance in BRAF-mutant melanoma cells. The EGF receptor confers BRAF inhibitor resistance in BRAF-mutant melanoma.

Fig. 4. BET inhibition sensitizes HR-proficient tumors to PARPi treatment in vivo. BET inhibition sensitizes HR-proficient tumors to PARPi treatment in.

Pharmacodynamic effects of PI3K inhibitor NVP-BKM120 on breast carcinomas in MMTV-CreBrca1f/fTrp53+/− mice. Pharmacodynamic effects of PI3K inhibitor NVP-BKM120.

Antitumor effect of local cancer immunotherapy treatment toward distant B16F10 tumors. Antitumor effect of local cancer immunotherapy treatment toward.

Fig. 4. Improved tumor response to docetaxel in TNBC and trastuzumab in HER2-amplified PDX models with the addition of S Improved tumor response.

Sequencing and PDX technologies for the identification and validation of therapeutic targets in non–V600 mutant BRAF melanoma. Sequencing and PDX technologies.

Core promoter methylation in mediators of adipogenesis.

Volume 18, Issue 8, Pages (February 2017)

B cells infiltrate mouse and human pancreatic neoplasia and promote growth of KrasG12D-PDEC in vivo. B cells infiltrate mouse and human pancreatic neoplasia.

CD8+ T cells were immunomodulated and required for the efficacy of anti–4-1BB/anti–PD-1 combination treatment. CD8+ T cells were immunomodulated and required.

Pharmacologic inhibition of eIF5A hypusination sensitizes KRas-driven tumor cells to MEK and KRas inhibition. Pharmacologic inhibition of eIF5A hypusination.

Effect of MI-773 and/or cisplatin in a preclinical model of ACC

Effect of MI-773 dosing on long-term efficacy.

Instigating, noninstigating, and responding human tumor specimens.

Vaccine MN confer protective innate and adaptive immunity.

Antitumor efficacy of PI3K inhibitor NVP-BKM120 alone and in combination with olaparib. Antitumor efficacy of PI3K inhibitor NVP-BKM120 alone and in combination.

CO-1686 does not inhibit WT EGFR signaling in vivo and is active in EGFR-mutant transgenic mouse lung cancer models. CO-1686 does not inhibit WT EGFR signaling.

CD8 T cells play a critical role in responses of TILs due to BRAF inhibition. CD8 T cells play a critical role in responses of TILs due to BRAF inhibition.

E-cadherin synthetic lethal effects operate in vivo in E-cadherin–defective breast tumors. E-cadherin synthetic lethal effects operate in vivo in E-cadherin–defective.

Effects of AG on the colon histology score in the acute DSS colitis model. Effects of AG on the colon histology score in the acute DSS colitis model. Ten.

Subcutaneous tumor growth was significantly increased in Ogt-Tg/+ mice

In vivo homing of intravenously injected CSNRDARRC peptide to bladder tumor in rats. In vivo homing of intravenously injected CSNRDARRC peptide to bladder.

The SFKs confer BRAF inhibitor resistance in BRAF-mutant melanoma cells. The SFKs confer BRAF inhibitor resistance in BRAF-mutant melanoma cells. A, phospho-protein.

Effects of DPM treatment on tumor volume, tumor mass, and pulmonary metastasis at experimental end point. Effects of DPM treatment on tumor volume, tumor.

Inhibitory effect of different doses of IP6 on prostate tumor progression in TRAMP mice. Inhibitory effect of different doses of IP6 on prostate tumor.

MiR-200c suppresses tumor growth and metastasis of CRC in vivo by targeting Sox2. MiR-200c suppresses tumor growth and metastasis of CRC in vivo by targeting.

Active AR signaling in enzalutamide-resistant xenograft tumors.

EMT gene expression patterns of M-Wnt and E-Wnt cells in vitro and in vivo. EMT gene expression patterns of M-Wnt and E-Wnt cells in vitro and in vivo.

Study overview. Study overview. A, Schematic illustrating clinical trial design and the nature and number of tissue specimens available for downstream.

PD-L1 expressed on edited T3 sarcoma cells prevents their immune elimination. PD-L1 expressed on edited T3 sarcoma cells prevents their immune elimination.

In vivo efficacy of targeted EDVTM in an orthotopic neuroblastoma mouse model with high EGFR protein levels. In vivo efficacy of targeted EDVTM in an orthotopic.

Antitumor effects of celastrol in vitro and in vivo.

ESKM is superior to ESK1 in vivo, and is effective against multiple tumor models. ESKM is superior to ESK1 in vivo, and is effective against multiple tumor.

A protracted ketogenic diet increases radiation response in H292 lung cancer xenografts given conventional fractionated radiation. A protracted ketogenic.

Ketogenic diets combined with fractionated radiation treatment results in decreased immunoreactive PCNA in tumor tissue. Ketogenic diets combined with.

The responses of H292 and A549 lung cancer xenografts to hypofractionated radiation were enhanced by the ketogenic diet. The responses of H292 and A549.

SY-1425 induces maturation in RARA-high AML

Ablation of Nf1 in HOXB7 lineage cells gives rise to diffuse cNF.

Derivation of the 4102 tumor cell lines.

Location of the ER mutations and frequencies per cohort.

Expression of PCNA, K10, and K5 in skin lesions from Stat3+/−:HPV8 and Stat3+/+:HPV8 mice. Expression of PCNA, K10, and K5 in skin lesions from Stat3+/−:HPV8.

Comparison of in vivo activity of 4D5scFvZZ and 4D5scFv.

Lapatinib cooperates with PLX4032 to inhibit BRAF-mutant thyroid cancer cell growth. Lapatinib cooperates with PLX4032 to inhibit BRAF-mutant thyroid cancer.

MGA271 exhibits potent in vivo antitumor activity toward tumor cell carcinoma xenografts. MGA271 exhibits potent in vivo antitumor activity toward tumor.

In vivo effects of TTFields on intradermal tumors in mice.

Targeting GAPLINC decreased CD44 expression and tumor growth in vivo.

Proliferation of TA3-Ha and TA3-St cells in vitro and in vivo.

PDL192 and inhibit the growth of xenograft tumors.

Ganetespib suppresses tumor growth and extends survival in ALK+ NSCLC xenografts. Ganetespib suppresses tumor growth and extends survival in ALK+ NSCLC.

Survival, subsequent therapies, and response.

Effects of ZOL treatment on pulmonary metastases.

GCS-100 selectively kills KRAS-addicted lung tumors.

Validation of KMT2D function in MM23, MM2, and MM25 PDXs

Core melanoma escape pathways during disease progression on BRAF inhibitor therapy. Core melanoma escape pathways during disease progression on BRAF inhibitor.

SCLC PDX models recapitulate patient responses to an experimental therapy. SCLC PDX models recapitulate patient responses to an experimental therapy. A,

Detection of microcalcifications in 4T1 mammary tumors and human breast tumor tissue. Detection of microcalcifications in 4T1 mammary tumors and human.

High genomic fidelity of SCLC PDX models derived from both CTCs and biopsies. High genomic fidelity of SCLC PDX models derived from both CTCs and biopsies.

Wnt5A and ROR2 contribute to intrinsic resistance to BRAF inhibitors.

PD-L1 expression is not associated with PTEN expression status in melanomas. PD-L1 expression is not associated with PTEN expression status in melanomas.

Coincidence and prognostic significance of PD-1+ and CD103+ cells in HGSC. Serial sections from the 490-case TMA were stained with antibodies to CD103.

Parthenolide inhibits tumor promotion and increases p21 expression in vivo. Parthenolide inhibits tumor promotion and increases p21 expression in vivo.

Presentation transcript:

Establishment of 12 PDX from BRAF inhibitor–progressed patients. Establishment of 12 PDX from BRAF inhibitor–progressed patients. A, schematic of BRAF inhibitor–resistant PDX generation, expansion, characterization, and in vivo testing. The arrow shown in blue outline denotes possible future clinical translation. B, PFS of patients is measured from first day on drug (vemurafenib/solid bar or dabrafenib/hatched bar) to progression by RECIST. Best response is denoted by the color of each bar: stable disease, light blue; partial response, blue; surgical complete response, green. Each bar represents one patient, 1/2 denote two samples collected from the same patient. C, PDX tumor grafts are followed from implantation until palpable; blue bars are untreated mice; and red bars are mice continuously dosed with BRAF inhibitor (PLX4720) diet. Mean of mouse cohorts (n > 5) is shown; error bars are SEM. D, growth rate of the same tumor grafts from palpable until sacrifice is calculated by maximum tumor volume in mm3/time in weeks, thus higher values indicate a faster growth rate; blue bars are untreated mice; and red bars are mice continuously dosed with BRAF inhibitor (BRAFi; PLX4720) diet. Mean of mouse cohorts (n > 5) is shown; error bars are SEM. E, histologic examination of patient tumor tissue used to generate the PDX and subsequent PDX passages harvested; WM3965-2 is shown as a representative model, all others are shown in Supplementary Fig. S2; MP1, first mouse passage; MP4, 4th serial transplantation in mice; on BRAFi, Rel., relative; mice were continuously dosed with BRAF inhibitor diet; H&E staining except PDX S100, a melanoma marker. Clemens Krepler et al. Clin Cancer Res 2016;22:1592-1602 ©2016 by American Association for Cancer Research