Heat-shock proteins are upregulated in
cancer and protect several client
proteins from degradation. Therefore, they contribute to
tumorigenesis and
cancer metastasis by reducing apoptosis and enhancing cell survival and proliferation. These client
proteins include the
estrogen receptor (ER),
epidermal growth factor receptor (EGFR),
insulin-like growth factor-1 receptor (IGF-1R),
human epidermal growth factor receptor 2 (HER-2), and
cytokine receptors. The diminution of the degradation of these client
proteins activates different signaling pathways, such as the PI3K/Akt/NF-κB, Raf/
MEK/ERK, and JAK/STAT3 pathways. These pathways contribute to hallmarks of
cancer, such as self-sufficiency in growth signaling, an insensitivity to anti-growth signals, the evasion of apoptosis, persistent angiogenesis, tissue invasion and
metastasis, and an unbounded capacity for replication. However, the inhibition of HSP90 activity by
ganetespib is believed to be a promising strategy in the treatment of
cancer because of its low adverse effects compared to other HSP90 inhibitors.
Ganetespib is a potential
cancer therapy that has shown promise in preclinical tests against various
cancers, including
lung cancer,
prostate cancer, and
leukemia. It has also shown strong activity toward
breast cancer,
non-small cell lung cancer,
gastric cancer, and
acute myeloid leukemia.
Ganetespib has been found to cause apoptosis and growth arrest in these
cancer cells, and it is being tested in phase II clinical trials as a first-line
therapy for metastatic
breast cancer. In this review, we will highlight the mechanism of action of
ganetespib and its role in treating
cancer based on recent studies.