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Advanced stage pancreatic cancer: novel therapeutic options
1Department of Medicine and Cancer Center, Tufts Medical Center, Tufts University School of Medicine, 800 Washington Street, Box 245, Boston, MA 02111, USA.
Abstract:
Despite advances in our understanding of the molecular and genetic basis of pancreatic cancer, it continues to be a therapeutic challenge. Gemcitabine approved by FDA in 1997, offers modest improvement of tumor-related symptoms and marginal advantage of survival. Many chemotherapeutic agents have been compared against or combined with gemcitabine in randomized Phase III trials and no drug was shown to be superior to single-agent gemcitabine except FOLFIRINOX and nab-paclitaxel plus gemcitabine. On the other hand, efforts to integrate targeted agents such as BAY 12-9566, SCH 66336, bevacizumab, cetuximab, axitinib and sorafenib have been quite dismal despite extensive pre-clinical and clinical research over the last decade in the field of novel agents. To date, erlotinib remains the only biological agent that has demonstrated a small, but significant, added benefit to single agent gemcitabine. However, numerous new agents, including monoclonal antibodies and tyrosine kinase inhibitors, are currently being tested in an attempt to achieve better response, while maintaining a safe toxicity profile. In this article, the author discusses the management of advanced pancreatic and the current role of novel agents in this setting.
Insights
Pancreatic cancer remains difficult to treat, with gemcitabine offering limited benefits. While many targeted therapies have failed, novel agents are being investigated for improved pancreatic cancer treatment outcomes.
Area of Science:
- Oncology
- Gastroenterology
- Pharmacology
Background:
- Pancreatic cancer presents significant therapeutic challenges despite advances in molecular and genetic understanding.
- Gemcitabine, FDA-approved in 1997, provides only modest symptom relief and marginal survival benefits for patients with pancreatic cancer.
- Numerous clinical trials combining or comparing chemotherapy agents with gemcitabine have yielded limited superior options beyond FOLFIRINOX and nab-paclitaxel plus gemcitabine.
Purpose of the Study:
- To review the current management strategies for advanced pancreatic cancer.
- To discuss the evolving role and efficacy of novel therapeutic agents in pancreatic cancer treatment.
- To highlight the challenges and future directions in developing effective pancreatic cancer therapies.
Main Methods:
- Review of randomized Phase III clinical trials evaluating chemotherapy and targeted agents in advanced pancreatic cancer.
- Analysis of pre-clinical and clinical research on novel agents, including monoclonal antibodies and tyrosine kinase inhibitors.
- Discussion of the clinical data for agents like FOLFIRINOX, nab-paclitaxel, and erlotinib in pancreatic cancer management.
Main Results:
- Most targeted agents (e.g., BAY 12-9566, bevacizumab, cetuximab) have shown dismal results in pancreatic cancer treatment.
- Erlotinib is the only biological agent to date providing a small but significant benefit when added to gemcitabine.
- FOLFIRINOX and nab-paclitaxel plus gemcitabine are notable exceptions demonstrating superiority over gemcitabine monotherapy.
Conclusions:
- The development of effective treatments for advanced pancreatic cancer remains a critical unmet need.
- Novel agents, including monoclonal antibodies and tyrosine kinase inhibitors, are under investigation to improve response rates and safety profiles.
- Continued research into novel therapeutic strategies is essential for advancing pancreatic cancer care and improving patient outcomes.
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