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Patients should be advised to report new or worsening neurological symptoms promptly, as these may indicate progressive deficiency requiring more aggressive intervention

Analogy to progressive somatic mutations in cancer evolution In cancer development and progression (for colon, breast, and lung malignancies), there appears to be an accumulation of a series of somatic mutations, typically involving loss of protective oncogenes or tumor suppressive factors and increases in cellular proliferative factors

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They typically occur in sun-exposed areas, although lesions in nonexposed areas have also been reported.28 Recently, Arnault et al.29 demonstrated that sorafenib produces paradoxical activation of the MAP kinase pathway, depending of the degree of activation, the duration of treatment, and the drug dose

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