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Emerging protein kinase inhibitors for treating pancreatic cancer
Junji Furuse1, Fumio Nagashima1
1a Department of Medical Oncology , Kyorin University, Faculty of Medicine , Tokyo , Japan.
Introduction:
Pancreatic cancer, the incidence and mortality of which are increasing around the world, has the most dismal prognosis among the commonly encountered cancers. Systemic chemotherapy plays an important role in the treatment of patients with pancreatic cancer, and development of more effective chemotherapies is being sought. Areas covered: This review article provides a summary about protein kinase inhibitors that have been investigated for the treatment of pancreatic cancer, not only existing agents targeting RAS, EGFR, VEGFR, MEK, etc., but also various compounds targeting, including the MAPK, PI3 K/Akt/mTOR, and JAK/STAT signaling pathways, trials of which are currently ongoing. To date, none has shown sufficient efficacy as to merit becoming established as a standard treatment agent for pancreatic cancer. Expert opinion: As the toxicities of protein kinase inhibitors usually differ from those of cytotoxic agents, it could be of value to use these agents in combination with gemcitabine plus nab-paclitaxel. It may be reasonable to identify a suitable disease and/or predictive markers for new compounds in proof of concept trials. It is an urgent need to conduct phase III trials, on the basis of the results obtained, in subpopulations with biomarkers to predict the efficacy of these drugs.
Insights
Protein kinase inhibitors show promise for pancreatic cancer treatment but lack sufficient efficacy alone. Combining them with standard chemotherapy may improve outcomes, with biomarker identification crucial for future trials.
Area of Science:
- Oncology
- Pharmacology
Background:
- Pancreatic cancer has a dismal prognosis with increasing global incidence and mortality.
- Systemic chemotherapy is vital, necessitating the development of more effective treatments.
Purpose of the Study:
- To review protein kinase inhibitors investigated for pancreatic cancer treatment.
- To summarize targeted signaling pathways and ongoing clinical trials.
Main Methods:
- Literature review of protein kinase inhibitors and their targeted pathways.
- Analysis of ongoing clinical trials for pancreatic cancer therapies.
Main Results:
- Various protein kinase inhibitors targeting RAS, EGFR, VEGFR, MEK, MAPK, PI3K/Akt/mTOR, and JAK/STAT pathways have been studied.
- Currently, no single agent has demonstrated sufficient efficacy for standard pancreatic cancer treatment.
Conclusions:
- Protein kinase inhibitors may be valuable in combination with gemcitabine plus nab-paclitaxel due to differing toxicities.
- Identifying predictive biomarkers is essential for future drug development and clinical trials, including urgent Phase III studies in biomarker-defined subpopulations.
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