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Ultrasound-Guided Orthotopic Implantation of Murine Pancreatic Ductal Adenocarcinoma
Published on: November 19, 2019
Precision medicine for KRAS wild-type pancreatic adenocarcinomas
Imen Ben-Ammar1, Adrien Rousseau2, Rémy Nicolle3
1Gustave Roussy, Département de Médecine, 94800 Villejuif, France; Sorbonne Université, Faculté de Médecine, 75005 Paris, France.
Background:
KRAS mutation is the most common molecular alteration in pancreatic adenocarcinoma (PDAC), and around 10% of patients harbor KRAS wild-type tumors (KRASWT).
Methods:
A retrospective chart review of clinical/molecular data was performed including all PDAC patients with a determined KRAS status (tumor molecular profiling on tissue or liquid biopsy).
Results:
342 patients were included with 54 KRASWT PDAC (16%) compared to 288 patients with KRASm PDAC. Median age was 61 years [IQR:54.0;67.0] and 164 pts (48%) were female. At diagnosis, KRASWT patients (63%) were more frequently diagnosed at a non-metastatic stage compared to KRASm patients (41%) (p = 0.003). Regarding metastatic sites, liver was less frequent in KRASWT (39%, p < 0.0001). Median overall survival (mOS) from initial diagnosis was significantly higher in the KRASWT group compared to KRASm (50.8 months, CI95% [32.0-NR] vs 21.1 months, CI95% [18.9-23.4] (p < 0.004 after adjustment on age, ECOG and stage at diagnosis). In first-line systemic treatment, (mostly FOLFIRINOX) progression-free survival (PFS) was also higher in KRASWT. Based on ESCAT classification, a putative actionable alteration (ESCAT I-III) was identified in 19 (36%) KRASWT pts and 46 (16%) KRASm patients (p < 0.0001) with more alterations in FGFR2, BRAF(V600E), NRTK and more MSI tumors. KRASWT harbored also fewer alterations in TP53, CDKN2A, and SMAD4. 12 KRASWT patients received a molecularly-matched treatment with clinical benefit and improved outcomes compared to KRASm patients.
Conclusions:
KRASWT patients display distinct disease characteristics and outcomes with prolonged overall survival. KRASWT patients also harbor more actionable molecular alterations, leading to higher survival rates after receiving molecularly matched treatments.
Insights
Patients with KRAS wild-type (KRASWT) pancreatic ductal adenocarcinoma (PDAC) have better outcomes and more actionable mutations. Molecularly-matched treatments improve survival in KRASWT PDAC patients.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- KRAS mutation is the most frequent molecular alteration in pancreatic ductal adenocarcinoma (PDAC).
- Approximately 10% of PDAC patients present with KRAS wild-type (KRASWT) tumors.
- Understanding the distinct characteristics of KRASWT PDAC is crucial for targeted therapy development.
Purpose of the Study:
- To investigate the clinical and molecular differences between KRAS wild-type and KRAS-mutated PDAC.
- To evaluate the impact of KRAS status on patient outcomes and treatment response.
- To identify actionable molecular alterations in KRASWT PDAC for personalized treatment strategies.
Main Methods:
- Retrospective chart review of clinical and molecular data from PDAC patients.
- Analysis of KRAS status (mutation or wild-type) using tissue or liquid biopsy.
- Comparison of demographic, clinical, and molecular features between KRASWT and KRAS-mutated groups.
Main Results:
- KRASWT PDAC patients were more frequently diagnosed at a non-metastatic stage (63% vs 41%).
- Liver metastasis was less common in KRASWT patients (39%).
- KRASWT patients exhibited significantly longer median overall survival (50.8 months vs 21.1 months) and improved progression-free survival.
- KRASWT tumors harbored more actionable molecular alterations (36% vs 16%), including FGFR2, BRAF(V600E), and NRTK.
- 12 KRASWT patients receiving molecularly-matched treatment showed clinical benefit and improved outcomes.
Conclusions:
- KRASWT PDAC is characterized by distinct disease features and superior overall survival.
- The higher prevalence of actionable molecular alterations in KRASWT PDAC offers opportunities for targeted therapies.
- Molecularly-matched treatments in KRASWT PDAC patients lead to improved survival rates.
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