Ras belongs to the family of small G-proteins and plays an important role in several signal transduction pathways involved in normal cell growth and differentiation. Over 30 years ago three isoforms of Ras – H-Ras, N-Ras, and K-Ras, have been identified for their oncogenic activation in human cancer cells. In fact aberrant Ras signaling could be shown in more than 30% of all human cancers including lung, colon, and pancreatic cancer. K-Ras has been identified as the most important Ras protein in cancer research.
As other small G proteins, Ras cycles between inactive (GDP-bound) and active state (GTP-bound) forms (see figure).
Although extensive research activities have been dedicated to Ras, no effective Ras inhibitor has been identified so far. But, there may be new hope in developing a therapeutic inhibitor to Ras proteins by targeting the upstream guanine nucleotide exchange factor (GEF) protein SOS (Son of sevenless).