For more than three decades,
platinum compounds have been the first line treatment for a wide spectrum of solid
tumors. Yet,
cisplatin resistance is a major impediment in
cancer therapy, and deciphering the mechanisms underlying chemoresistance is crucial for the development of novel
therapies with enhanced efficacy. The Rho subfamily of
small GTPases plays a significant role in
cancer progression, and a growing body of evidence points toward the involvement of these
proteins in anticancer drug resistance, including
cisplatin resistance. The cycling between active and inactive states, governed by the balance between their GEFs, GAPs and
GDIs, RhoGTPases, acts as molecular switches with a pivotal role in actin cytoskeleton organization. The Rho subfamily of
proteins is involved in many key cellular processes including adhesion, vesicular trafficking, proliferation, survival, cell morphology and cell-matrix interactions. Although RhoA, RhoB and RhoC are highly homologous and share some upstream regulators and downstream effectors, they each have different roles in
cancer progression and chemoresistance. While RhoA and RhoC are upregulated in many
tumors and can stimulate transformation, RhoB appears to exhibit
tumor suppressor characteristics with proapoptotic effects. In the current review, we discuss the role of Rho subfamily of
proteins in
cancer, and focus on their involvement in intrinsic and acquired drug resistance.