Therapeutic Application of Monoclonal Antibodies in Pancreatic Cancer: Advances, Challenges and Future Opportunities

Abstract

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.

Factors Affecting the Readmission of Patients with Pancreatic Cancer after Surgery

“…Pancreatic cancer is one of the deadliest human cancers [1] and has a very poor 5-year survival rate [2]. Studies have shown that smoking, alcohol consumption, dietary factors, diabetes, obesity, and genetics are important factors associated with the incidence of pancreatic cancer [3,4].…”

In Vitro Tumor Cell-Binding Assay to Select High-Binding Antibody and Predict Therapy Response for Personalized 64Cu-Intraperitoneal Radioimmunotherapy against Peritoneal Dissemination of Pancreatic Cancer: A Feasibility Study

“…Antibody arrays, which have been variously developed for biomarker detection in pancreatic cancer [ 36 , 37 ], might be applied in the 64 Cu-TuBA format in the future. Thus far, no pancreatic cancer-specific therapeutic antibodies have been approved for the treatment of pancreatic cancer despite the effort of previous studies; that is, it is difficult to cover most pancreatic cancer patients by targeting one specific target antibody [ 38 ]. Therefore, personalized 64 Cu-ipRIT with 64 Cu-TuBA could be a beneficial strategy for pancreatic cancer treatment.…”

Positive clinical outcomes following therapy with programmed cell death protein 1/programmed cell death ligand 1 inhibitors in neuroendocrine carcinoma of the cervix

“…Pembrolizumab can bind to PD-1, antagonize PD-1 interaction with its ligands, and enable the immune system to eliminate cancer cells ( Sahni et al, 2018 ). The first tissue-agnostic/site-agnostic medication, pembrolizumab is effective for treating melanoma, NSCLC, recurrent or metastatic cervical cancer, metastatic SCLC, endometrial carcinoma, TMB-H solid tumors, MSI-H or dMMR CRC, triple-negative breast cancer expressing PD-L1 and other types of cancer ( Arias-Pinilla and Modjtahedi 2021 ). In addition, the NCCN guidelines state pembrolizumab can be considered a second-line or subsequent treatment for cervical malignancies that are PD-L1 positive, MSI-H/dMMR, and TMB-H recurrent or metastatic ( NCCN Guidelines 2022 ).…”