Is There A Link Between Skin and Brain Cancers?

There are many types of cancer affecting people today. While some types of cancer are treatable, others are not. When it comes to treatment options, there are a wide variety of treatment options available, though some types of cancer can prove to be fatal regardless of whatever treatment is provided. Understanding what is the underlying mechanism of cancer growth can be crucial to developing a more focused treatment that can save lives. A recent study has now put the focus on a mechanism of action that may influence the development of cancer. Understanding this pathway and how it works could help develop newer treatments while also establishing if there is a link between skin and brain cancers.

A recent study published in October 2022 in the Nature Structural and Molecular Biology journal looked at a certain molecular pathway that can be found in various cancer types. This includes basal cell carcinoma of the skin (one of the most common forms of skin cancer) and medulloblastoma, which is the most common brain tumor observed in children. ^(1,2,3)

Cancer was the second leading cause of death in the US in 2020, and experts all over the world are continuing to work on understanding what triggers and contributes to the growth, development, and spread of cancer in certain people. ⁽⁴⁾ Over the years, researchers have gathered some data on some of the risk factors for certain types of cancer so that people can understand the risks better and also work towards taking preventive action. ⁽⁵⁾ At the same time, the treatment options for cancer have gone up substantially in recent years, with the advent of more targeted therapies becoming available, which cause less damage to the rest of the body. ⁽⁶⁾ Cancer treatments today revolves around a combination of various treatments, including immunotherapy, radiation therapy, hormonal therapy, or surgery. And to develop newer, more innovative treatments with a better success rate and fewer side effects, researchers are working hard to gain a better understanding of the exact biological mechanisms that go on inside to increase a person’s risk of developing cancer in the first place. Researching what takes place at the molecular and cellular levels can help find new targets for treatment.

The authors of the study researched the key signaling pathway in organ development, which is known as the Hedgehog pathway. ^(7,8,9) In certain people, under activity of the Hedgehog pathway has been associated with birth defects, while over-activation of the pathway has been linked to the growth of certain cancers. The study, led by Dr. Benjamin Myers from the University of Utah School of Medicine, focused on a system in the body known as the signaling pathway, which is used by cells in the body to help pass on critical information from the outside of the cell to the inside. ⁽¹⁰⁾

The Hedgehog signaling pathway is extremely critical in the correct development of tissues and organs in the body. Any errors in this signaling pathway can cause cancers or birth defects, including some pediatric brain tumors and some common skin tumors.

The study focused on the smoothened protein (SMO), and it was discovered that the protein physically blocks one of the most important signaling enzymes in the Hedgehog pathway, known as the PKA catalytic subunit (PKA-C). ⁽¹¹⁾ The lack of PKA-C leads to the release of certain gene-regulating proteins that are typically inhibited as well as the promotion of the Hedgehog pathway.

For the last so many years, experts were aware that the Hedgehog pathway played many important roles in the development of organs and diseases, though there was no clear understanding of how the pathway actually worked, what type of molecular signal was getting encoded, and how was the signal traveling from the outside of the cell to the inside. The new study helped find answers to this longstanding question and revealed that the underlying molecular basis for how the signals travel through the Hedgehog pathway.

The study found that the mechanism of how tumors grow in the body is when one signal on the surface of the tumor cell initiates a signaling program that starts making the tumors grow in an uncontrolled manner. The study also discovered a new and innovative mechanism whereby the signaling through the Hedgehog passes through the PKA-C in order to activate the pathway. This, in turn, opened up a new understanding of how the pathway works and towards the potential development of a new drug target. ⁽¹²⁾

The study provided substantially significant findings, and it proved to be an important step forward toward understanding the underlying mechanism in particular cancer development. However, the biggest limitation of the study was that it used only mouse and cellular models, due to which it only provided a certain level of data. Further research is going to be important in converting this information and bringing it to clinical practice. Future research will continue to focus on confirming the role of the Hedgehog signaling pathway and how it impacts the growth of cancer. This pathway can potentially be used as a target for new drug development in an attempt to prevent the activation of tumor growth programs.

The data from this study can help usher in the development of more targeted cancer treatments as the study helped explain clearly at a molecular level how any errors in the Hedgehog signaling can cause birth defects or cancer. Armed with this knowledge, researchers and clinicians can better understand diseases like cancer at a more basic level. In the near future, this type of research can help enable the development of new kinds of medications to correct the faulty Hedgehog signaling events that take place in cancer and also provide therapeutic benefits to cancer patients.

Achieving this was very challenging in the past owing to the lack of information about how the Hedgehog pathway functioned at a molecular level. However, the insights provided by this study can help realize the long-term therapeutic benefits of correcting the faults in the Hedgehog signaling pathway.

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