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Molecular Profiling in Pancreatic Cancer: Current Role and Its Impact on Primary Surgery
Carmen Mota Reyes1,2,3, Alper Doğruöz1,4, Rouzanna Istvanffy1,2,3
1Department of Surgery, Klinikum Rechts der Isar, Technical University of Munich, School of Medicine, Munich, Germany.
Background:
The advent of next-generation sequencing technologies has enabled the identification of molecular subtypes of pancreatic ductal adenocarcinoma (PDAC) with different biological traits and clinically targetable features.
Summary:
Although current chemotherapy trials are currently exploiting this knowledge, these molecular subtypes have not yet sufficiently caught the attention of surgeons. In fact, integration of these molecular subtypes into the timing of surgery can in theory improve patient outcome. Here, we present the molecular subtypes of PDAC from the surgeon's perspective and a clinically applicable algorithm that integrates the molecular subtyping of PDAC preoperatively into the decision of primary surgery versus neoadjuvant therapy. Furthermore, we point out the potential of "tailored" (in addition to conventional) neoadjuvant treatment for exploiting the molecular subtypes of PDAC.
Key Messages:
We believe that for surgeons, the preoperative knowledge on the subtype of PDAC can properly guide in deciding between upfront surgery versus neoadjuvant treatment for improving patient outcome.
Insights
Molecular subtypes of pancreatic ductal adenocarcinoma (PDAC) can guide surgical decisions. Integrating molecular subtyping preoperatively can optimize treatment timing and improve patient outcomes.
Area of Science:
- Oncology
- Genomics
- Surgical Oncology
Background:
- Next-generation sequencing identifies molecular subtypes of pancreatic ductal adenocarcinoma (PDAC).
- These subtypes exhibit distinct biological characteristics and potential therapeutic targets.
- Current research primarily focuses on chemotherapy, with limited surgical integration.
Purpose of the Study:
- To present molecular subtypes of PDAC from a surgical perspective.
- To introduce a preoperative algorithm for integrating molecular subtyping into surgical decisions.
- To highlight the potential of tailored neoadjuvant therapies based on molecular subtypes.
Main Methods:
- Review and synthesis of current knowledge on PDAC molecular subtypes.
- Development of a clinically applicable algorithm for preoperative molecular subtyping.
- Discussion of neoadjuvant treatment strategies tailored to molecular subtypes.
Main Results:
- Molecular subtypes of PDAC can inform surgical timing and treatment selection.
- A preoperative algorithm can guide decisions between primary surgery and neoadjuvant therapy.
- Tailored neoadjuvant treatments offer potential for improved outcomes.
Conclusions:
- Preoperative molecular subtyping of PDAC is crucial for surgeons.
- This knowledge aids in selecting the optimal treatment strategy (upfront surgery vs. neoadjuvant therapy).
- Personalized neoadjuvant approaches based on molecular subtypes can enhance patient outcomes.
