Ideal for: Efficacy studies with PDX tumor heterogeneity, mechanisms of chemotherapy (platinum) resistance, clinical trial design and co-clinical trials, cancer initiating cell studies (CIC)

Epithelial ovarian cancer is the most lethal gynecologic malignancy. Recurrence and resistance to standard platinum-based chemotherapy results in poor survival. This published collection of 31 Ovarian and 21 Endometrial PDX models, include different ethnic backgrounds, RNA-seq and mouse data, display varying sensitivities to platinum-based therapies has been utilized in the discovery of key characteristics and potential interventions. The large majority of the tumors tested also correlate with the patient’s platinum response therapies, presenting an opportune collection for both efficacy studies in discovery and clinical trial design (1-3).

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PDX collection products & services

  • Xenograft efficacy studies, including collection of blood, tissues and tumor for ADME, PK/PD and analysis.
  • Co-clinical trials for trial design and patient selection
  • OncoRats off-the-shelf for engraftment at the customers facility

In one example, the ovarian PDX model collection has been used to identify Wnt/β-catenin as a novel driver of platinum resistance by maintaining stem-like properties. Targeted inhibition of this pathway overcame platinum resistance by eliminating CICs.

Enabling Case Study: PDX tumor kinetics and response to platinum

PDX tumor, Hera-OV07, generated from a patient who was deemed platinum-resistant, was inherently resistant to platinum-based therapies compared to Hera-OV03, which was isolated from a patient who was platinum-sensitive.

ENDOMETRIAL CANCER

IDAge-EthnicitySubtypeStageGradeSample collectedSequencing availableMouse study
Hera-END0163-BlackSerousIV3Omental MetRNA seq, Exome sequencing (patient) 
Hera-END0252-WhiteRecurrent EndometriodRecurrent3ascites Y
Hera-END0383-BlackRecurrent SerousRecurrent3AscitesRNA seq, Exome sequencing (patient and PDX)Y
Hera-END0478-WhiteSerousIA3Ascites  
Hera-END0559-WhiteEndometriodIVb2Adnexal MetRNA seq, Exome sequencing (patient and PDX)Y
Hera-END0666-WhiteSerousIV3metastatic LN tumor  
Hera-END0765-BlackSerousIVb3omental tumorRNA seq, Exome sequencing (patient and PDX)Y
Hera-END0847-WhiteRecurrent LeiomyosarcomaRecurrent3pelvic mass Y
Hera-END0949-BlackEndometriodIIIC13uterine tumorRNA seq, Exome sequencing (patient)Y
Hera-END1082-WhiteSerousIVb3small bowel noduleRNA seq, Exome sequencing (patient) 
Hera-END1154-WhiteRecurrent EndometriodRecurrent1pelvic massRNA seq, Exome sequencing (patient and PDX)Y
Hera-END12BlackClear CellIIIC13Uterine tumor  
Hera-END1386-WhiteSerousIB3Endometrial tumorRNA seq, Exome sequencing (patient) 
Hera-END1462-Blackneuroendocrine tumor of the uterus (small cell)IB3Peritoneal nodule  
Hera-END1559-WhiteSerousIVb3Colon nodule tumorRNA seq, Exome sequencing (patient) 
Hera-END1667-WhiteSerousIV3peritoneal biopsyRNA seq, Exome sequencing (patient) 
Hera-END17BlackEndometriodIIIC13uterine tumor/pelvic LN  
Hera-END1859-BlackSerousIA3uterine tumor  
Hera-END1966-WhiteEndometriodIA3uterine tumor  
Hera-END2051-WhiteEndometriodIV2peritoneal nodule  
Hera-END2167-WhiteSarcoma 3uterine tissueRNA seq, Exome sequencing (patient and PDX)

OVARIAN CANCER

IDAge-EthnicitySubtypeStageGradeSample collectedOptimal/Suboptimal debulkingBRCA1/2 statusSequencing availableMouse study
Hera-OV0137-WhiteSerousIV3AscitesOptimalBRCA1 p.R762fs (GERMLINE)RNA seq, Exome sequencing (patient and PDX)Y
Hera-OV0256-BlackRecurrent Villoglandular Papillary EndometrioidIA3lymph node tissue with cancer; recurrentOptimal   
Hera-OV0357-WhiteSerousIIIC3Ascites (from Paracentesis) BRCA2 mutation- c.475+1G>T (GERMLINE)RNA seq, Exome sequencing (patient and PDX)Y
Hera-OV0464-WhiteSerousIV3AscitesOptimal   
Hera-OV0560-WhiteClear CellIIIC3Pelvic MassOptimal RNA seq, Exome sequencing (patient and PDX) 
Hera-OV0653-Whiteserous borderlineIIIA23Ovarian tumorOptimalBRCA2 p.V2728I (GERMLINE VUS)RNA seq, Exome sequencing (patient) 
Hera-OV0782-WhitecarcinosarcomaIIIC3Ovarian tumorOptimalBRCA2 p.T1915M (GERMLINE VUS)RNA seq, Exome sequencing (patient and PDX)Y
Hera-OV0865-WhiteserousIV3omentumOptimalBRCA1 (GERMLINE)  
Hera-OV0964-Whiterecurrent endometriodIIIC3skin noduleN/A   
Hera-OV1061-WhiteserousIV3ovarian tumoroptimal   
Hera-OV1168-BlackserousIIIC3TumorOptimal   
Hera-OV1261-BlackserousIIIC3TumorOptimal   
Hera-OV1358-Whitemixed high grade serous (60%) and poorly differentiated endometrioid (40%)IIIC3Omental noduleOptimal RNA seq, Exome sequencing (patient) 
Hera-OV1490-Whitelow-grade serousIV1Ascites    
Hera-OV1551-WhiteendometriodIIIC3Rectus muscle tumorSuboptimal  Y
Hera-OV1669-BlackserousIV3Ovarian tumorOptimalBRCA1 p.S1140G (GERMLINE VUS)RNA seq, Exome sequencing (patient and PDX) 
Hera-OV1753-WhiteserousIV3AscitesOptimal   
Hera-OV1858-WhiteClear cellIIIC3TumorSuboptimal   
Hera-OV1959-WhiteserousIIIC3Omental nodule tumorOptimalBRCA1 p.S1040N (GERMLINE VUS)RNA seq, Exome sequencing (patient) 
Hera-OV2049-WhiteserousIV3Omental nodule tumorOptimalBRCA 2 p.A2951T (GERMLINE VUS)RNA seq, Exome sequencing (patient) 
Hera-OV2159-WhiteserousIIIC3peritoneal noduleOptimalBRCA1 p.A1690P (SOMATIC)RNA seq, Exome sequencing (patient) 
Hera-OV2257-WhiteserousIIIC3omentumOptimalBRCA2 p.N3124I (GERMLINE)RNA seq, Exome sequencing (patient and PDX)Y
Hera-OV2337-Whiteserous borderlineIIIB3portion of adnexaOptimal RNA seq, Exome sequencing (patient) 
Hera-OV2448-WhiteserousIIIC3OmentumSuboptimalBRCA1 p.Y1874fs and p.Q356R (GERMLINE)RNA seq, Exome sequencing (patient) 
Hera-OV2563-WhiteendometriodIA3portion of adnexaOptimal   
Hera-OV2674-WhiteserousIIIC3small bowel nodule BRCA1 p.S1040N (GERMLINE VUS)  
Hera-OV2737-WhiteserousIII3omental noduleOptimal RNA seq, Exome sequencing (patient)Y
Hera-OV2874-BlackserousIIIC3peritoneal bx  RNA seq, Exome sequencing (patient) 
Hera-OV2956-WhitemucinousIIB2portion of adnexaOptimal   
Hera-OV3060-WhiteserousIIIC3peritoneal bx    
Hera-OV3143-WhiteserousIV3omental noduleOptimalBRCA1 p.Arg1443Ter (GERMLINE) 
  1. Nagaraj et al. (2015) Critical role of Wnt/β catenin signaling in driving epithelial ovarian cancer platinum resistance. Oncotarget V. 6, N. 27.
  2. Dimitrova et al. (2016) InFlo: a novel systems biology framework identifies cAMP-CREB1 axis as a key modulator of platinum resistance in ovarian cancer. Oncogene 1-11.
  3. Hudson et al (2016) Altered glutamine metabolism in platinum resistant ovarian cancer. Oncotarget V., N. 27