New Kaposi sarcoma mouse model could be key to drug development

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Researchers astatine UNC Lineberger Comprehensive Cancer Center, aft decades of investigation efforts, person developed a rodent exemplary of Kaposi sarcoma that could beryllium cardinal to nan improvement of caller narcotics to dainty nan disease. Kaposi sarcoma is simply a crab that is nan astir communal crab successful group surviving pinch HIV.

The findings appeared successful Cell Host & Microbe.

This is an important improvement arsenic we person created nan first animal exemplary ever of Kaposi sarcoma. Animal models are basal to move caller narcotics from nan laboratory chair into objective trials. Before this, only repurposed narcotics from different cancers were utilized to dainty Kaposi sarcoma, but now we tin commencement investigating wholly caller compounds to thief dainty what tin beryllium a lethal cancer."

Dirk Dittmer, PhD, elder corresponding author, co-leader of nan UNC Lineberger Virology Research Program and head of nan UNC Viral Genomics Core

About 20% of each quality cancers originate from viruses aliases require viral infection arsenic an basal cofactor. The Kaposi sarcoma-associated herpes microorganism (KSHV) was discovered successful 1994 and is associated pinch Kaposi's sarcoma arsenic good arsenic B-cell cancers. KSHV-associated diseases impact soul organs and are yet fatal. In nan U.S., nan diseases are recovered chiefly successful immunosuppressed group specified arsenic those who are HIV-positive aliases are transplant patients.

Worldwide, an estimated 34,270 cases of Kaposi sarcoma were diagnosed, and 15,086 deaths reported successful 2020, pinch doubly arsenic galore cases and deaths occurring successful men compared to women. Africa accounted for 73% of caller cases and 86.6% of nan deaths from Kaposi sarcoma worldwide. The illness is endemic, and not HIV-related, successful immoderate confederate and eastbound African countries.

Aside from animal models, 1 measurement to study crab is to look astatine tumor cells successful nan lab. But according to Dittmer, Kaposi sarcoma tumor cells are very finicky and limited connected signaling molecules and humor supply, which is why they don't past successful a laboratory civilization dish. Therefore, researchers person been focusing connected processing animal models that would mimic, arsenic intimately arsenic possible, nan illness successful humans.

One of nan challenges nan researchers faced successful processing their exemplary was nan truth that 2 types of genes are transcribed into proteins successful nan Kaposi sarcoma rodent model. Normally erstwhile a microorganism infects a cell, nan compartment dies arsenic nan microorganism replicates, which is simply a process called compartment lysis; nan genes that are needed for nan microorganism to propagate itself are lytic genes. Cancer viruses are different arsenic they participate a quiet state, called latency, wherever only nan genes that thief nan infected compartment past are expressed. The rodent exemplary nan researchers developed is analyzable arsenic a spot of some types of genes were needed.

Cervical crab and its related virus, HPV (human papilloma virus), offers a bully comparison for nan situation of processing a Kaposi sarcoma rodent model. The KSHV genome is 20 times larger than HPV. HPV has 2 cancer-causing genes, E6 and E7, truthful to mimic nan illness successful animals, researchers only needed to creation 2 mice, 1 for each gene. KSHV whitethorn person arsenic galore arsenic 10 cancer-causing genes that each activity together truthful it would beryllium measurement excessively difficult to create that galore mice, hence nan kindness of their azygous model, Dittmer noted.

"Another of nan cardinal virtues of our caller rodent exemplary is that it helps america understand angiogenesis, aliases caller humor alloy formation. Without angiogenesis crab cells are deprived of oxygen and die," Dittmer said. "In this rodent model, we tin study angiogenesis blocking narcotics amended than ever before. If caller narcotics activity against Kaposi sarcoma, they will besides apt activity against lesser-angiogenic tumors, which would beryllium a awesome plus."

For adjacent steps, nan researchers dream that others will prosecute supplier and vaccine improvement based connected a caller knowing of basal aspects of KSHV provided by their rodent model, including imaginable improvement of a much-needed primate exemplary for quality KSHV and Kaposi sarcoma.

Source:

Journal reference:

Sin, S.-H., et al. (2024). The complete Kaposi sarcoma-associated herpesvirus genome induces early-onset, metastatic angiosarcoma successful transgenic mice. Cell Host & Microbe. doi.org/10.1016/j.chom.2024.03.012.