The body’s function of generating new cells and replacing dead ones usually works fine, but it is by no means perfect. The key to generating new cells is communication or signaling between cells, and if this process does not function properly, it can lead to uncontrolled cell growth, which is the basis for many cancers.
A key discovery made by scientists from the Texas University Health Science Center at Houston (UTHealth) Medical School reveals that cell signaling plays an important role in the fight against melanoma and various other fast-spreading tumors.
The study is published online ahead of the June 5 edition of Current Biology.
About 9,000 people die each year from melanoma (skin cancer), according to the American Cancer Society. The researchers have now discovered the reason as to why BRaf inhibitors, which are frequently used for the treatment of skin cancers do not always work, and most significantly, how these drugs can possibly speed up the growth of cancer in certain patient populations.
Senior author John Hancock, M.B, B.Chir, Ph.D., a John S. Dunn Distinguished University Chair in Physiology and Medicine and chairman of the Department of Integrative Biology and Pharmacology, who is also interim director of the Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases at the UTHealth Medical School declared:
“This information may aid the development of more effective anti-cancer drugs and better inform the choice of new combinations of drugs.”
A chain of proteins that forms a signaling pathway transmits growth signals from a cell’s surface to the nucleus, whilst the command for dividing cells in order generate new cells is relayed by a chain of four proteins, namely RAS, BRaf, MEK and ERK. This pathway is shared by all cells and is generally very effective, yet difficulties occur when one of the first proteins in the chain is mutated, as both proteins lock the pathway in the ‘on’ position.
BRaf inhibitors are drugs that block the signaling from the second protein, and are successful in treating melanomas with mutant BRaf proteins. However, so far, there are no inhibitors available that can block the first protein (RAS). The team conducted in vivo studies to explore what happens when BRaf inhibitors are applied to human cancer tissues with Ras mutations.
Kwang-jin Cho, Ph.D., the study’s lead author and research fellow at the UTHealth Medical School declared:
“Surprisingly recent studies found that BRaf inhibitors do not block signaling in melanoma cells with Ras mutations. In fact, the drugs actually enhance the abnormal signaling activity. Our work now describes the mechanism for this seemingly paradoxical enhanced signaling activity.”
The majority of melanomas either have a mutation of the BRaf protein or of the Ras protein, yet they seldom feature both. Mutations of the RAS protein cause an otherwise normal BRaf protein to remain switched ‘on’.
Cho concluded:
“Our study also emphasizes the importance of genetic testing of melanomas before using BRaf inhibitors. Our study may also help design a better drug.”
Written By Petra Rattue