Approximately 50% of ERMS is associated with RAS mutations, with NRAS mutations more common in adolescent cases and HRAS and KRAS mutations occurring in 70% of infant cases. Embryonal rhabdomyosarcoma is commonly driven by a mutation in the RAS family of proto-oncogenes, creating a powerful signal which is now known to promote tumor growth by preventing muscle lineage progression by blocking expression of the transcription factor myogenin. Inhibition of this signaling pathway with a cancer medication, trametinib, has been recently shown to overcome this differentiation block and reduce tumor progression in animal models of embryonal rhabdomyosarcoma.Tumor suppressor gene mutations, such as TP53 mutations, were shown in about 13% in the mutations and MYOD1 mutations were seen in about 3% of the mutations. Tumor suppressors signal the cell to stop the cell cycle and start apoptosis, known as programmed cell death, when the cell senses damage or irregular cell cycle growth patterns. Approximately 10% of ERMS cases include a loss of function mutation at TP53, which results in anaplasia, poor cellular differentiation that can be identified through nuclei that are larger and darker-colored than normal. An international study of more than 600 people with RMS showed worst outcomes in cases with anaplasia, regardless of fusion-status. Predisposing Conditions
Genetic conditions such as Gorlin syndrome, neurofibromatosis type 1, Beckwith-Wiedemann syndrome, Li-Fraumeni syndrome, Noonan syndrome, Costello syndrome, and DICER1 syndrome have been shown to predispose individuals to embryonal rhabdomyosarcoma. Risk factors associated with embryonal rhabdomyosarcoma include cigarette smoking, older age of birth parent, x-ray exposure, and maternal drug use.
Efavirenz/lamivudine/tenofovir (EFV/3TC/TDF), sold under the brand name Symfi among others, is a fixed-dose combination antiretroviral medication for the treatment of HIV/AIDS. It combines efavirenz, lamivudine, and tenofovir disoproxil. As of 2019, it is listed by the World Health Organization as an alternative first line option to dolutegravir/lamivudine/tenofovir. It is taken by mouth.Side effects can include joint pain, sleepiness, headaches, depression, trouble sleeping, and itchiness. Severe side effects may include depression, psychosis, or osteonecrosis. In those with a history of epilepsy, it may increase the frequency of seizures. Greater care should also be taken in those with kidney problems. Its use during pregnancy appears to be unsafe.It is on the World Health Organizations List of Essential Medicines. The combination received tentative approval in the United States in 2014, and was granted approval in February 2018. Its availability and importance is supported by Medecins Sans Frontieres. It is available as a generic medication. References
External links
"Efavirenz". Drug Information Portal. U.S. National Library of Medicine. "Lamivudine". Drug Information Portal. U.S. National Library of Medicine. "Tenofovir disoproxil". Drug Information Portal. U.S. National Library of Medicine. "Tenofovir disoproxil fumarate". Drug Information Portal. U.S. National Library of Medicine.