PAK in Pancreatic Cancer-Associated Vasculature: Implications for Therapeutic Response.

Cells

Department of Surgery, Austin Precinct, The University of Melbourne, 145 Studley Rd, Heidelberg, VIC 3084, Australia.

Published: November 2023

Angiogenesis has been associated with numbers of solid tumours. Anti-angiogenesis drugs starve tumours of nutrients and oxygen but also make it difficult for a chemo reagent to distribute into a tumour, leading to aggressive tumour growth. Anti-angiogenesis drugs do not appear to improve the overall survival rate of pancreatic cancer. Vessel normalisation is merging as one of the new approaches for halting tumour progression by facilitating the tumour infiltration of immune cells and the delivery of chemo reagents. Targeting p21-activated kinases (PAKs) in cancer has been shown to inhibit cancer cell growth and improve the efficacy of chemotherapy. Inhibition of PAK enhances anti-tumour immunity and stimulates the efficacy of immune checkpoint blockades. Inhibition of PAK also improves Car-T immunotherapy by reprogramming the vascular microenvironment. This review summarizes current research on PAK's role in tumour vasculature and therapeutical response, with a focus on pancreatic cancer.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10705971PMC
http://dx.doi.org/10.3390/cells12232692DOI Listing

Publication Analysis

Top Keywords

anti-angiogenesis drugs
8
pancreatic cancer
8
inhibition pak
8
tumour
5
pak pancreatic
4
pancreatic cancer-associated
4
cancer-associated vasculature
4
vasculature implications
4
implications therapeutic
4
therapeutic response
4

Similar Publications

Association of VEGFR2 Polymorphisms with Clinical Outcomes of Anti-angiogenesis Therapy in Cancer Patients: A Systematic Review and Meta-analysis.

Eur J Pharmacol

January 2025

Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang 110840, China; Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address:

Background: Some cancer patients derive limited benefit from anti-angiogenic therapy or discontinuation due to adverse reactions. Vascular endothelial growth factor receptor 2 (VEGFR2) plays an important role in regulating angiogenesis in tumors. This study aims to evaluate the association of VEGFR2 polymorphisms with clinical outcomes of anti-angiogenic drugs (AADs) in cancer patients.

View Article and Find Full Text PDF

Dual-drug loaded chondroitin sulfate embolization beads enhance TACE therapy for HCC by integrating embolization, chemotherapy, and anti-angiogenesis.

Mater Today Bio

February 2025

State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Sciences & Medical Engineering, Southeast University, Nanjing, 210009, China.

Hepatocellular carcinoma (HCC) is a major public health threat due to its high incidence and mortality rates. Transcatheter arterial chemoembolization (TACE), the primary treatment for intermediate-to-advanced hepatocellular carcinoma (HCC), commonly utilizes embolic agents loaded with anthracycline-based cytotoxic drugs. Post-TACE, the hypoxic microenvironment in the tumor induced by embolization stimulates the formation of new blood vessels, potentially leading to revascularization and diminishing TACE's efficacy.

View Article and Find Full Text PDF

Objectives: GPC3 has been recognized as a promising target for immunotherapy in hepatocellular carcinoma (HCC). However, the GPC3-targeted immunotherapies have shown limited therapeutic efficacy. The use of anti-PD-1/PD-L1 monoclonal antibodies in HCC treatment is considerably constrained.

View Article and Find Full Text PDF

Combination therapy with anti-angiogenic drugs and immune checkpoint inhibitors has shown enhanced clinical activity and has been approved for the treatment of multiple tumor types. Despite extensive research, predictive biomarkers for combination therapy remain poorly understood. Microvessel density (MVD), a surrogate marker for aberrant angiogenesis measured by immunohistochemistry (IHC), has been associated with response to monotherapy with anti-angiogenesis inhibitors.

View Article and Find Full Text PDF

Background: The vascular endothelial growth factor (VEGF) signaling pathway is closely related to pathological angiogenesis in liver disease. Anti-angiogenesis is an effective intervention in the clinical treatment of liver disease. Some antiangiogenic drugs are resistant and have limitations in clinical use.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!