H-ras Oncogene Mutation and Human Papillomavirus Infection in Oral Carcinomas

The molecular pathogenesis of head and neck squamous cell carcinoma

“…While it is currently unknown whether HRAS-dependent signals function in collaboration with or independently of PI3K activation in HNSCC, several findings underscore the importance of this particular RAS family member to the pathogenesis of the disease. These include the more frequent occurrence of HRAS than KRAS mutations in HNSCC, particularly in relationship to tobacco history, whereas the reverse is true for several other malignancies (74,75); the presence of HRAS mutations in HPV-driven tumors, suggesting potential cooperativity in tumor promotion (76); and the more frequent association of HRAS versus KRAS mutation in squamous cell carcinomas arising in the setting of tobacco exposure in humans and chemical carcinogen exposure in mice (77). Although Ras proteins themselves have proven difficult to target directly, therapeutic strategies that target downstream effectors of Ras proteins or the synthetic lethal dependencies that result from their mutational activation have already been successful in preclinical models (78)(79)(80).…”

Advances in Chemoprevention of Head and Neck Cancer

“…A mutation in the H-ras gene is found in 27%-61% of squamous cell carcinoma cases and 30% of cases of oral leukoplakia [53,54]. FTIs inhibit an enzymatic step in the expression of this gene and have been shown to have extensive activity in preclinical studies using HNSCC cell lines, as well as in nonsmall cell lung cancer lines.…”

Treatment of Head and Neck Squamous Cell Carcinoma According on the Specific Molecular Features of the Tumor (A Literature Review)

“…Сигнал Ras может взаимодействовать с активированной ки-назой PI3K или проявляться независимо в развитии ПРГШ, который зачастую ассоциирован с мутациями HRAS, особенно у курящих больных ПРГШ [25]. Как и PI3K, мутации HRAS ассоциированы с ВПЧ-пози-тивными опухолями [29]. Амплификации или мутации гена PI3K выявлены у 56 % ВПЧ-позитивного ПРГШ и в 34 % случаев ВПЧ-негативных опухолей [13].…”