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New discoveries about a key signaling pathway could eventually lead to better cancer treatments. Image credit: VICTOR TORRES/Stocksy.
  • Cancer encompasses a wide variety of types. Treatment options vary, and some forms of cancer can be fatal.
  • Understanding the underlying mechanisms of cancer growth can be vital to developing treatment.
  • A recent cell study has highlighted a mechanism of action that may influence cancer development.

Cancer is a disease where the cells of the body grow uncontrollably and can invade other parts of the body. These cells can destroy healthy cells by blocking essential nutrients and changing the function of organs.

Cancer impacts millions of people in the United States alone. Treatment options have improved in recent decades, but many underlying mechanisms of cancer remain unknown.

A​ recent study published in Nature Structural & Molecular Biology explored a specific molecular pathway that may underlie several cancer types, including basal cell carcinoma of the skin, which is the most common form of skin cancer, and medulloblastoma, the most common brain tumor affecting children.

Understanding how this pathway works could open the door for new cancer treatment options.

I​n 2020, cancer was the second leading cause of death in the U.S. Experts are still working to understand what triggers and contributes to cancer development and growth.

Researchers have collected some data on risk factors for specific cancer types so that people can understand their risks and work to take preventative steps.

Treatment options for cancer have increased in recent decades, with more targeted therapies becoming available that cause less damage to the rest of the body. Cancer treatment can involve a combination of several treatments, such as radiation, immunotherapy, hormone therapy, or surgery.

To develop new treatments with greater success rates and fewer side effects scientists are working to better understand the biological mechanisms which can increase an individual’s risk of developing the disease.

Studying what happens at the cellular and molecular levels can identify new targets for treatment.

Researchers involved in this study looked at a key signaling pathway in organ development, known as the Hedgehog pathway. Underactivity of this pathway has been linked to birth defects, while overactivation has been shown to drive certain cancers.

Study author Dr. Benjamin Myers, assistant professor in the Department of Oncological Sciences at the Huntsman Cancer Institute, University of Utah School of Medicine, explained the underlying mechanism of interest in this current study.

“This study was focusing on a system in our bodies known as a ‘signaling pathway.’ A signaling pathway is a bit like a ‘telephone wire’ in our cells that helps relay important information from the outside of the cell to the inside,” he explained.

“The signaling pathway that we are studying, known as ‘Hedgehog,’ is very important in helping our tissues and organs develop correctly. Also, errors in this signaling pathway can lead to birth defects or cancers, including some fairly common skin tumors and pediatric brain tumors,” the study author further noted.

Researchers focused on the Smoothened protein (SMO). They found that the SMO protein physically blocks a key signaling enzyme in the Hedgehog pathway called the PKA catalytic subunit (PKA-C).

The lack of PKA-C causes the release of gene-regulating proteins which are usually inhibited and the promotion of the Hedgehog pathway.

D​r. Myers explained:

“For many years, scientists knew that Hedgehog played all these critical roles in development and disease but didn’t understand how the actual ‘telephone wire’ worked — what type of molecular signal was encoded, and how did it travel from the outside of the cell to the inside? Our study helps to resolve this longstanding mystery by revealing the underlying molecular basis for how Hedgehog signals travel along this ‘telephone wire’.”

Dr. Santosh Kesari, director of neuro-oncology at Providence Saint John’s Health Center and chair of the Department of Translational Neurosciences and Neurotherapeutics at Saint John’s Cancer Institute in Santa Monica, CA, who was not involved in this study, offered a further explanation to Medical News Today.

“This study elaborates on the mechanism of how these tumors grow when a signal on the surface of the tumor cell initiates a signaling program that makes these grow uncontrolled. They found a novel mechanism whereby hedgehog signaling goes through PKA-C to activate the pathway. This opens up a new understanding and possible a new drug target,” he told us.

The study offered significant findings and is a critical step towards understanding an underlying mechanism in particular cancer development. However, it only utilized mouse and cellular models, which can only provide a certain level of information. Further research is going to be essential when it comes to translating this information into clinical practice.

D​r. Kesari noted: “Future research will focus on confirming this signaling pathway and how it affects tumor growth. This pathway can be looked at as a target for drug development to try to prevent this activation of tumor growth program.”

Ideally, the data from this study can help to forward the development of more targeted cancer treatments. Dr. Myers was optimistic about what they had found and what it could mean for the future.

“Our study helps to explain at a molecular level how errors in Hedgehog signaling can lead to birth defects or cancer. Having this knowledge help scientists and clinicians understand these diseases at a more fundamental level. In the future, our research may enable new types of drugs to correct the faulty Hedgehog signaling events that occur in cancer and thereby provide therapeutic benefit to cancer patients in the clinic,” he said.

“This was very difficult in the past due to a lack of knowledge about how the Hedgehog pathway worked at a molecular level, but the insights provided by our study may help to realize this long-term therapeutic goal in the future,” added Dr, Myers.