Title:Anti-VEGF Mediated Immunomodulatory Role of Phytochemicals: Scientific Exposition for Plausible HCC Treatment
Volume: 22
Issue: 11
Author(s): Ayana R. Kumar, Aswathy R. Devan, Bhagyalakshmi Nair and Lekshmi R. Nath*
Affiliation:
- Department of Pharmacognosy, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Ponekkara P.O., Kochi, Kerala 682041,India
Keywords:
Hepatocellular carcinoma, vascular endothelial growth factors, phytoconstituents, immunotherapy, neutrophils, cytotoxic
T cells, regulatory T cells.
Abstract: Hepatocellular carcinoma (HCC) is one of the most common solid tumours and the second
leading cause of cancer-related mortality worldwide. Advanced-recurrent HCC often requires
a systemic drug therapy where multi tyrosine kinase inhibitor, Sorafenib represents the first-line
therapy option. But it exhibited very limited survival benefit and tumour response due to the early
emergence of drug resistance and drug-related adverse effect. Immunotherapy approaches now being
widely studied as an effective alternative treatment for HCC. Several immune checkpoint inhibitors
(ICI), such as Nivolumab and Pembrolizumab, are approved as monotherapy in
sorafenib-resistant HCC patients. But, the existence of a plethora of immunosuppressive signals in
the tumour microenvironment often leads to unsuccessful immunotherapies. In this context, combinatorial
immunotherapies are getting much acceptance as a way to improve therapeutic outcomes
by blocking immunosuppressive signals in the tumour microenvironment (TME). The combination
of Vascular Endothelial Growth Factor (VEGF) inhibitors with ICI resulted in significant
synergistic effects in various preclinical and clinical studies. However, the adverse effects associated
with current synthetic VEGF inhibitors limit its clinical utility. In this review, we have summarized
the potential of phytochemicals, especially the category of flavonoids, alkaloids,
glycosides, terpenoids, and coumarin, as the available-affordable-safe-effective repositories of
VEGF inhibitors. Their possibilities as an alternative for synthetic VEGF inhibitors by synergistic
combination with ICI are reviewed, thereby enhancing patient compliance and survival rates. This
review highlights the demand for a detailed investigation of the plausible role of plant-based
anti-angiogenic-immunotherapy combination against HCC.
