Molecular chaperones, or heat shock proteins (Hsps), are integral to protein production, protection from environmental stress, and identification of proteins for degradation. One, Hsp90, has been implicated in oncogenesis, as it is overexpressed in many tumors and may protect them from chemotherapy and radiation.
They may have use as monotherapies, though they probably will be used in combination with chemotherapy and radiotherapy, since blocking Hsp90 should render malignant cells more sensitive to these treatments. Trojantec has developed a derivative of the p21 gene to counter the effects of Hsp90.
The Hedgehog pathway provides an intercellular regulatory mechanism that serves essential functions in the normal proliferation and differentiation of stem cells. Mutations in this pathway figure in basal cell carcinoma, medulloblastoma, and other malignancies. Three drugs that interfere with hedgehog signaling are in clinical trials—two, Infinity Pharmaceuticals’ IPI-926 and Genentech/Curis’ GDC-0449, are derivatives of cyclopamine, which has been studied extensively.