Circulating KRAS G12D but not G12V is associated with survival in metastatic pancreatic ductal adenocarcinoma
These videos have been matched automatically. Contact us if they are not relevant.
These videos have been matched automatically. Contact us if they are not relevant.
View abstract on PubMed
Summary
This summary is machine-generated.Circulating KRAS G12D tumor DNA (ctKRAS) levels and their clearance are linked to survival in metastatic pancreatic cancer (mPDAC). ctKRAS G12D, but not G12V, serves as a prognostic biomarker.
Area Of Science
- Oncology
- Molecular Biology
- Biomarker Discovery
Background
- High circulating tumor DNA (ctDNA) levels correlate with poor survival across many cancers.
- Variant-specific differences in ctDNA association with survival remain underexplored.
- KRAS mutations are common in pancreatic ductal adenocarcinoma (PDAC).
Purpose Of The Study
- To investigate KRAS ctDNA (ctKRAS) variant-specific associations with overall survival (OS) and progression-free survival (PFS).
- To evaluate ctKRAS G12D and G12V as prognostic biomarkers in first-line metastatic PDAC (mPDAC).
- To assess the utility of early ctKRAS clearance as a response biomarker.
Main Methods
- Analysis of ctKRAS variant-specific levels and survival in the PRINCE trial (chemoimmunotherapy) and an independent standard-of-care (SOC) chemotherapy cohort.
- Kaplan-Meier analysis and Cox regression to assess associations with OS and PFS.
- Evaluation of baseline ctKRAS levels and on-therapy clearance.
Main Results
- Higher baseline ctKRAS G12D levels associated with worse OS in PRINCE (p=0.0010), unlike G12V (p=0.7101).
- Early clearance of ctKRAS G12D strongly associated with improved OS (p=0.0002), but not G12V (p=0.4058).
- Similar findings were observed in the SOC cohort and for PFS in both cohorts.
Conclusions
- ctKRAS G12D, but not G12V, is a promising prognostic biomarker for mPDAC.
- Early G12D clearance may serve as an early biomarker of treatment response.
- Variant-specific ctDNA analysis is crucial for understanding prognostic and predictive value in mPDAC.
These videos have been matched automatically. Contact us if they are not relevant.
These videos have been matched automatically. Contact us if they are not relevant.
Related Concept Videos
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...