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The trend toward more target therapy in pancreatic ductal adenocarcinoma
Chiara Deiana1, Margherita Agostini1, Giovanni Brandi1,2
1Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
Introduction:
Despite the considerable progress made in cancer treatment through the development of target therapies, pancreatic ductal adenocarcinoma (PDAC) continues to exhibit resistance to this category of drugs. As a result, chemotherapy combination regimens remain the primary treatment approach for this aggressive cancer.
Areas Covered:
In this review, we provide an in-depth analysis of past and ongoing trials on both well-known and novel targets that are being explored in PDAC, including PARP, EGFR, HER2, KRAS, and its downstream and upstream pathways (such as RAF/MEK/ERK and PI3K/AKT/mTOR), JAK/STAT pathway, angiogenesis, metabolisms, epigenetic targets, claudin, and novel targets (such as P53 and plectin). We also provide a comprehensive overview of the significant trials for each target, allowing a thorough glimpse into the past and future of target therapy.
Expert Opinion:
The path toward implementing a target therapy capable of improving the overall survival of PDAC is still long, and it is unlikely that a monotherapy target drug will fulfill a meaningful role in addressing the complexity of this cancer. Thus, we discuss the future direction of target therapies in PDAC, trying to identify the more promising target and combination treatments, with a special focus on the more eagerly awaited ongoing trials.
Insights
Pancreatic ductal adenocarcinoma (PDAC) remains resistant to targeted therapies. This review analyzes current and future trials for various targets, emphasizing combination treatments for improved patient survival.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Pancreatic ductal adenocarcinoma (PDAC) shows significant resistance to targeted therapies, necessitating combination chemotherapy regimens.
- Despite advances, effective targeted drug monotherapy for PDAC remains elusive due to cancer complexity.
Purpose of the Study:
- To review past and ongoing clinical trials for established and novel therapeutic targets in PDAC.
- To analyze the efficacy of various targeted agents and combination strategies.
- To identify promising future directions for PDAC targeted therapy.
Main Methods:
- Comprehensive analysis of clinical trial data for PDAC targets.
- In-depth review of targets including PARP, EGFR, HER2, KRAS pathways, JAK/STAT, angiogenesis, metabolism, epigenetics, claudin, P53, and plectin.
- Evaluation of trial outcomes to assess therapeutic potential.
Main Results:
- Numerous targets are under investigation, including well-known and novel agents.
- Combination therapies are increasingly recognized as crucial for overcoming PDAC resistance.
- Ongoing trials are exploring diverse therapeutic strategies and combinations.
Conclusions:
- Targeted therapy for PDAC is complex and unlikely to be solved by monotherapy.
- Future research should focus on identifying optimal combination treatments and promising novel targets.
- Careful selection of targets and combinations is essential for improving overall survival in PDAC patients.
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