1. In 1971, Alfred Knudson Jr. studied the kinetics with which bilateral and unilateral retinoblastomas appeared in children. He determined that the bilateral occurred with one-hit kinetics, whereas the unilateral tumors occurred with two-hit kinetics. Each hit was believed to represent a somatic mutation. This gives reason that cancer is the result of multiple mutations.
2. FTI’s usually function by blocking the enzyme that links the 15 carbon farnesyl lipid group to recently synthesized H- and K-Ras protein molecules. Out of the four Ras proteins (H-, N-, and two K-Ras proteins), H-Ras is the only protein that depends entirely on its farnesyl group for function. N-Ras and K-Ras have alternative lipid groups attached to their C-termini such as geranylgeranyl, which allow them to continue to function as normal. Also, H-Ras oncoprotein is activated in less than 5% of tumor containing Ras oncogenes. This limits the efficacy of any FTIs that might be successively developed. These protein links may explain why FTIs are not effective inhibitors in such cancers as osteosarcoma. To counter this, the next target would be geranylgeranyl and like lipid groups that may attach to these Ras proteins.
3. Diagnosis and death rates are independent of each other. Although the chance of being diagnosed with either of these...