Researchers at UNC Lineberger Comprehensive Cancer Center have created a model of Kaposi sarcoma that could help speed up the process of developing new drugs to treat the disease, which is the most common cancer in individuals with HIV. The findings were published in Cell Host & Microbe. This advancement is critical in the fight against Kaposi sarcoma and could lead to the creation of new drugs for treatment.The first animal model of Kaposi sarcoma has been developed, which is crucial for testing new drugs in clinical trials, according to Dirk Dittmer, PhD, senior corresponding author at UNC Lineberger. Previously, only repurposed drugs from other cancers were used to treat Kaposi sarcoma, but now researchers can explore completely new compounds to combat this potentially lethal cancer. Around 20% of human cancers are either caused by viruses or depend on viral infection as a necessary factor.The Kaposi’s sarcoma-associated herpes virus (KSHV) was first identified in 1994 and is linked to Kaposi’s sarcoma and B-cell cancers. KSHV-related diseases affect the body’s organs and are ultimately fatal. In the U.S., these diseases are mainly found in people with weakened immune systems, such as those who are HIV-positive or have had organ transplants.
Globally, an estimated 34,270 cases of Kaposi’s sarcoma were diagnosed in 2020, with 15,086 reported deaths. Men had twice as many cases and deaths compared to women. Africa accounted for 73% of new cases and 86.6% of the deaths from Kaposi’s sarcoma worldwide. The disease is widespread in Africa and is not related to HIV.Researchers in some parts of Africa have been looking for ways to study cancer, particularly Kaposi sarcoma, which is a type of cancer commonly found in southern and eastern African countries. One method of studying cancer is to examine tumor cells in a lab setting, but Kaposi sarcoma tumor cells are difficult to work with because they are highly dependent on signaling molecules and blood supply, making it hard for them to survive in a laboratory culture dish. That’s why researchers have been focusing on creating animal models that closely resemble the disease in humans. One challenge they faced in developing the model was the fact that two types of genes are transcribed into proteins in the Kaposi sarcoma mouse model.Normally when a virus infects a cell, the cell dies as the virus replicates, a process called cell lysis; the genes required for the virus to replicate itself are lytic genes. Unlike cancer viruses, which enter a dormant state called latency, where only the genes that help the infected cell survive are activated. The mouse model created by the researchers is complex, as it required a combination of both types of genes.
When compared to cervical cancer and its associated virus, HPV (human papilloma virus), developing a Kaposi sarcoma mouse model presents a significant challenge. The KSHV genome is 20 times larger than HPV. HPV has two.The researchers created two mice, one for each of the cancer-causing genes E6 and E7, to replicate the disease in animals. KSHV may have up to 10 cancer-causing genes that work together, making it difficult to develop that many mice. Therefore, the single model created by the researchers has great value, according to Dittmer.
Dittmer also highlighted that the new mouse model is beneficial for understanding angiogenesis, which is the formation of new blood vessels. Dittmer explained that without angiogenesis, cancer cells do not receive enough oxygen and die. The mouse model allows for better study of angiogenesis blocking drugs, providing a more effective way to test new drugs.Kaposi’s sarcoma, they are also likely to be effective against less-angiogenic tumors, which would be a major advantage.”
As the next steps, the researchers are hopeful that others will pursue drug and vaccine development based on a new understanding of the fundamental aspects of KSHV provided by their mouse model. This could also include the potential development of a much-needed primate model for human KSHV and Kaposi’s sarcoma.
Â
