| 摘要 |
Disclosed herein are methods for treating a subject with, or at risk for, developing a tumor which has aberrantly increased Ras signaling. The method involves obtaining a biological sample from the subject, determining whether the biological sample contains cells which have aberrantly increased Ras signaling, and administering an agent that selectively inhibits Protein Kinase C (PKC) delta to the subject upon determination of the aberrantly increased Ras signaling, to thereby inhibit PKC-delta in the cell. The increased Ras signaling may result from expression of activated Ras, e.g. resulting from mutations in codon 12, 13, 59, 61, 63, 116, 117, or 146. Such mutations can be determined by detection of a nucleotide sequence encoding an activated form of Ras protein, or by detection of the activated Ras protein. The increased Ras signaling may result from over-expression of wild-type Ras, over-activation of wild-type Ras, or increased activation of one or more effector pathways downstream of Ras. The tumor cells of the individual may be malignant or non-malignant. The inhibitor(s) of PKC-delta may inhibit PKC-delta gene expression, reduce PKC-delta protein levels, and/or inhibit PKC-delta protein function by inhibiting kinase activity. Appropriate inhibitors are Rottlerin, Balanol, balanol analogs, KAI 9S03, and combinations thereof. Also disclosed are methods for determining the likelihood of effectiveness of administering an agent that selectively inhibits PKC-delta to a subject with a tumor. The methods involve determining the presence or absence of aberrantly increased Ras signaling in the tumor, wherein the presence of aberrantly increased Ras signaling indicates that administration of the PKC-delta inhibitor is likely to be effective.
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