The Hedgehog Signaling Pathway and Cancer Therapy
Cancer researchers based in Switzerland have uncovered a method to inhibit the development of malignant colon cancer. This process can keep the disease from growing into late-stage cancer and metastasizing throughout the body. The experimental data establishes that halting the genetic mutation known as “the Hedgehog-GLI pathway” can preclude the expansion of malignant growths and stop the creation of cancer stem cells in the body. Cancer stem cells are believed to be the main cause of most cancer development and growth. Although this research does not target mesothelioma specifically, any advances in cancer treatment are welcome in the fight against asbestos cancer.
Cancer of the colon frequently starts out as a tumor along the wall of the bowels. In the early stages, the disease is treatable with surgery and chemotherapy. If the disease is not detected early, it can metastasize and spread cancerous cells throughout the vital abdominal organs such as the liver, pancreas and intestines. A group of scientists from Geneva, Switzerland, has identified the crucial factor that the Hedgehog-GLI pathway brings in the advancement of the disease in the later stages.
This specific genetic pathway, also known as HH-GLI, is the method that cells use to pass information among themselves in order to regulate cell growth and mortality rates. HH-GLI is a necessary part of human growth during gestation and childhood. In most instances, the pathway shuts off when a person reaches full physical maturity. However, the pathway can also restart when a patient develops cancer. When that occurs, the HH-GLI pathway feeds into the growth and metastasis of cancer cells.
According to the leader of the Geneva research team, Dr. Ariel Ruiz i Altaba, other groups had carried out efforts to determine the nature of how HH-GLI reacts with colon cancer, but those studies did not come up with a conclusive answer. In the Geneva study, Dr. Ruiz i Altaba stated that their efforts have established the idea that HH-GLI is critical for the onset and maturation of colon cancer cells. The results from the Geneva research also show that HH-GLI pathways encourage the growth of other tumors that have spread to other organs from the malignant colon cells.
Scientists are also working on a new type of chemotherapy that could potentially inhibit the HH-GLI pathway and suppress the growth of cancer cells. New cancer therapy techniques, such as the chemotherapy drug Cyclopamine and gene therapy that interferes with the tumor’s molecular structure, have been found to stop the HH-GLI pathway from sending signals to nearby cell clusters. Advances such as this could open up new treatment options for patients with advanced stages of colon cancer.
Another way that this new research can help cancer patients is in how attacking the HH-GLI pathway can prevent recurrences of the previous cancer in patients who have shown signs of recovery. In an experiment conducted on laboratory mice, the Geneva research team found that mice treated with Cyclopamine did not show signs of recurrence and remained free of tumors after being administered the drug for one year. The mice treated with Cyclopamine also did not exhibit any of the major side effects associated with other chemotherapy treatments.
Some other types of cancer, such as basal cell carcinoma (skin cancer) and medulloblastoma (brain cancer), are highly reliant on the HH-GLI molecule to spur on their growth and expansion. A group of researchers from the Johns Hopkins School of Medicine in Baltimore, Maryland used another form of HH-GLI inhibitor to attack a patient’s brain cancer that had spread to other parts of the body. Up to that point, the patient had undergone numerous surgical procedures, chemotherapy treatments and radiation exposures to deal with the disease.
Dr. Charles Rudin, leader of the research team, treated the patient with a drug called GDC-0449 for two months. Within that short timeframe, the patient exhibited a remarkable decrease in the number of tumors. Eventually, however, the tumor cells developed a resistance to the drug and the tumors returned. While the group’s research was promising at first, their results led to the conclusion that the drug may not be sufficient by itself to treat such virulent and aggressive forms of cancer. Instead, they reasoned, GDC-0449 is best used in conjunction with other traditional cancer therapy methods.
Another group of scientists on the other side of the country conducted tests using GDC-0449 on patients with advanced skin cancers. A team of researchers from Scottsdale HealthCare Center in Arizona used the HH-GLI inhibitor drug on more than thirty patients with advanced basal cell carcinoma. During the ten months of the study, only four patients reported any advances in their disease and none reported any debilitating side effects.
As with all cancer research, efforts are still ongoing and no “silver bullets” have yet been discovered. However, scientists are continuing to pursue the avenue of hedgehog inhibitors and are optimistic about the potential of new drugs that can target and slow down the growth of the most aggressive and deadly forms of cancer.
Sources: AZCentral.com, WebMD, ScienceDaily.com
