The Proteoglycan Glypican-1 as a Possible Candidate for Innovative Targeted Therapeutic Strategies for Pancreatic Ductal Adenocarcinoma

Abstract

Pancreatic ductal adenocarcinoma (PDAC) accounts for 90% of all pancreatic cancers, with a 5-year survival rate of 7% and 80% of patients diagnosed with advanced or metastatic malignancies. Despite recent advances in diagnostic testing, surgical techniques, and systemic therapies, there remain limited options for the effective treatment of PDAC. There is an urgent need to develop targeted therapies that are able to differentiate between cancerous and non-cancerous cells to reduce side effects and better inhibit tumor growth. Antibody-targeted strategies are a potentially effective option for introducing innovative therapies. Antibody-based immunotherapies and antibody-conjugated nanoparticle-based targeted therapies with antibodies targeting specific tumor-associated antigens (TAA) can be proposed. In this context, glypican-1 (GPC1), which is highly expressed in PDAC and not expressed or expressed at very low levels in non-malignant lesions and healthy pancreatic tissues, is a useful TAA that can be achieved by a specific antibody-based immunotherapy and antibody-conjugated nanoparticle-based targeted therapy. In this review, we describe the main clinical features of PDAC. We propose the proteoglycan GPC1 as a useful TAA for PDAC-targeted therapies. We also provide a digression on the main developed approaches of antibody-based immunotherapy and antibody-conjugated nanoparticle-based targeted therapy, which can be used to target GPC1.

Value of Glypican-1 Expression in Pleural Epithelioid Mesothelioma, Adenocarcinoma and Squamous Cell Carcinoma of the Lung

“…Concerning lung SCC cases, GPC1 expression tumors such as oesophageal and pancreatic cancer [15,16]. Few previous studies were conducted to evaluate GPC1 expression levels in pleural mesothelioma and lung carcinoma.…”

Oral Administration of Cancer Vaccines: Challenges and Future Perspectives

“…TAAs are self antigens that are highly expressed by tumour cells and absent or low in normal tissues. NY-ESO1 and Glypican-1 (GPC1) are examples of TAAs [ 5 , 6 ]. NY-ESO1, also called New York oesophageal squamous cell carcinoma 1, belongs to the cancer testis antigens (CTAs).…”

“…It consists of a GPI anchor, a C-terminal, an N-terminal domain, and a secretory signal peptide. It is considered a TAA because it has low expression in adult tissues under physiological conditions but can be overexpressed in cancers, such as pancreatic ductal adenocarcinoma (PDAC), where it plays a role in supporting mitogenic stimuli [ 6 ]. The initial development of parenteral cancer vaccines focused on TAAs due to their versatility and potential for broad applicability across diverse patient populations [ 8 ].…”

Discovery of potent and noncovalent KRASG12D inhibitors: Structure-based virtual screening and biological evaluation

“…In addition, the tumor is resistant to all forms of routine clinical treatment. It is estimated that pancreatic cancer will become the second leading cause of cancer-related deaths by 2030 (Bazhin et al, 2014;Busato et al, 2022), which highlights the need to develop new treatment drugs to improve the survival rate of patients with pancreatic cancer. KRAS (Kirsten Ras protein) was found to be the most common locus for somatic gain-of-function mutations in patients with pancreatic cancer, accounting for about 95% (Morris et al, 2010;Eibl and Rozengurt, 2019).…”

“…In addition, the tumor is resistant to all forms of routine clinical treatment. It is estimated that pancreatic cancer will become the second leading cause of cancer-related deaths by 2030 ( Bazhin et al, 2014 ; Busato et al, 2022 ), which highlights the need to develop new treatment drugs to improve the survival rate of patients with pancreatic cancer.…”