Increasingly, there is more evidence pointing towards the inhibition of neuropilin-1 activity in slowing the progression of tumours in several types of cancers.
Cancer is a multifaceted disease that can be very difficult to diagnose or even treat at advance stages. Discovery of new therapeutic targets against cancer has been of focus in biomedical research for decades. At present, together with advancements in research methods, our fundamental understanding of the mechanisms of cancer development and proliferation have increased. This has opened more doors for better diagnostic methods and more promising avenues for cancer treatment.
In a new review article published in Chinese Medical Journal, scientists from Guangxi Medical University, China, have organized and analysed the latest papers published on the cell receptor neuropilin-1 (NRP-1) and its potential as a treatment target for many cancers. Their work provides a much-needed overview of the salient findings in this field that helps direct future research on cancer treatment.
Neuropilins are transmembrane protein receptors with many functions in the body. They act as part of cell signalling pathways, regulating cellular function when various ligands (proteins) bind to them. NRP-1 is critical to nerve cell and heart and blood vessel development and is otherwise found to be expressed on the surface of many types of cells, including regulatory T cells (a type of immune cell), osteoblasts (bone forming cells), adipocytes (fat storage cells), keratinocytes (a type of skin cell), and bone marrow fibroblasts (connective tissue in the bone marrow).
Its critical roles in cell growth and blood vessel formation (angiogenesis) have granted this receptor involvement in development and proliferation of cancer. NRP-1 can form complexes with various growth factors, helping the cancer cells to multiply and promote tumour proliferation and metastasis. On top of this, NRP-1 would bind to a protein expressed on regulatory T cells, an important player in anti-tumour immunity. The binding would interfere with T cell functioning, speeding up tumour progression. It is also able to promote the action of tumour-associated macrophages, which suppresses the body’s normal immune system, helping the tumour to proliferate. The involvement of NRP-1 in blood vessel formation in tumours allows for its continued growth and nourishment through the capillary network.
The combination of these roles by NRP-1 in tumour progression makes it an attractive target in cancer treatment. Several therapeutic strategies have already been developed, including blocking the interaction of NRP-1 with growth factors to prevent tumour blood-vessel formation, preventing NRP-1 presence in tumour regulatory T cells so that cancers are more susceptible to the body’s immune system, and directly targeting NRP-1 expression in several types of cells.
Other, more cutting-edge technologies include the development of alternative splicing variants which are basically mutant versions of original proteins that bind to NRP-1; these variants change how NRP-1 acts when they bind to it. Some studies have also investigated combining multiple drugs that target NRP-1 or administering NRP-1-related drugs along with existing chemotherapy drugs. These studies have found that such “combination therapies” work well to eliminate multiple types of cancers.
Lead author of the article, Dr Liu Shao-Dan, discusses the importance of reviewing recent progress in research on NRP-1 and its relationship to cancers. “A comprehensive review gives us a better sense of where we are now and what still needs to be known. For example, a lot of questions remain to be answered about the exact molecular mechanisms of NRP-1 action in cancer progression.” Said Dr Liu.
Nonetheless, recent NRP-1 research has considerably increased our understanding of this receptor’s role in tumour development and enhanced our ability to predict the likely outcome of cancers, in addition to diagnosing and treating them. Dr Liu adds, “We also hope that reading about all these advancements in cancer treatments will give the public confidence that cancer research is on the right track.” [APBN]