Abstract
Simple SummaryPancreatic cancer is a leading cause of cancer death worldwide. In the majority of patients, cancers are diagnosed at advanced stages of disease and are resistant to current treatments. Therefore, more effective and less toxic therapeutic agents are urgently needed. Monoclonal antibody (mAb)-based technology is an important tool in the discovery of novel therapeutic targets and development of novel therapeutic agents including antibody-based drugs. In this article, we review the therapeutic potential of monoclonal antibody-based agents when used as single agents or in combination with other treatments in pancreatic cancer, factors contributing to the poor response to therapy and emerging opportunities for more effective treatment with antibody-based agents. Pancreatic cancer remains as one of the most aggressive cancer types. In the absence of reliable biomarkers for its early detection and more effective therapeutic interventions, pancreatic cancer is projected to become the second leading cause of cancer death in the Western world in the next decade. Therefore, it is essential to discover novel therapeutic targets and to develop more effective and pancreatic cancer-specific therapeutic agents. To date, 45 monoclonal antibodies (mAbs) have been approved for the treatment of patients with a wide range of cancers; however, none has yet been approved for pancreatic cancer. In this comprehensive review, we discuss the FDA approved anticancer mAb-based drugs, the results of preclinical studies and clinical trials with mAbs in pancreatic cancer and the factors contributing to the poor response to antibody therapy (e.g. tumour heterogeneity, desmoplastic stroma). MAb technology is an excellent tool for studying the complex biology of pancreatic cancer, to discover novel therapeutic targets and to develop various forms of antibody-based therapeutic agents and companion diagnostic tests for the selection of patients who are more likely to benefit from such therapy. These should result in the approval and routine use of antibody-based agents for the treatment of pancreatic cancer patients in the future.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) is one of the most common and aggressive cancer types, with a five-year survival rate of only 2–9% [1]
The results of the recently published ESPAC-4 trial showed that the combination of gemcitabine plus capecitabine increased median overall survival compared to gemcitabine alone (28.0 vs 25.5 months) with an acceptable toxicity profile, and an estimated 5-year survival of 28.8% for the combination group compared to 16.3% with gemcitabine monotherapy, making this combination the new standard of care in the adjuvant setting [7]
The combination of liposomal irinotecan, fluorouracil and folinic acid (NAPOLI-1 regimen) is the only currently approved second-line chemotherapy for patients with metastatic pancreatic cancer based on a phase 3 trial that showed median overall survival of 6.1 months for the triple combination compared to 4.2 months in patients receiving fluorouracil and folinic acid [12]
Summary
Pancreatic ductal adenocarcinoma (PDAC) is one of the most common and aggressive cancer types, with a five-year survival rate of only 2–9% [1]. Erlotinib was approved by the FDA for use in metastatic pancreatic cancer patients based on a study that showed a modest improvement in median survival in patients who received erlotinib plus gemcitabine compared to gemcitabine alone (6.4 vs 5.9 months) but the clinical relevance is controversial [11]. The combination of liposomal irinotecan, fluorouracil and folinic acid (NAPOLI-1 regimen) is the only currently approved second-line chemotherapy for patients with metastatic pancreatic cancer based on a phase 3 trial that showed median overall survival of 6.1 months for the triple combination compared to 4.2 months in patients receiving fluorouracil and folinic acid [12]. We shall highlight some of the contributing factors for the poor response to therapy with mAbs, and emerging opportunities for more effective treatment of pancreatic cancer with antibody-based agents in combination with other treatments
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