review · International Journal of Molecular Sciences
Heat-shock proteins, especially HSP90, are elevated in cancer cells and protect key client proteins from degradation. These protected proteins, including receptors such as EGFR and HER-2, drive cancer growth, cell survival, and metastasis through critical signalling networks. Ganetespib is an HSP90 inhibitor that counteracts these processes by inducing apoptosis and halting cell division in malignant cells. Compared to earlier HSP90 inhibitors, ganetespib exhibits fewer adverse side effects, making it a promising therapeutic candidate. Preclinical evaluations demonstrate strong anti-cancer activity across multiple malignancies, including prostate cancer, non-small cell lung cancer, gastric cancer, and acute myeloid leukaemia. Furthermore, ganetespib has progressed into human testing, currently undergoing phase II clinical trials as a first-line treatment for metastatic breast cancer. This positioning highlights its broad therapeutic potential across diverse tumour types.
Cancer cells rely on heat-shock proteins to maintain the stability of proteins that fuel rapid tumour growth and resist standard therapies. By selectively disrupting HSP90 with reduced toxic side effects, treatments using ganetespib offer a potential pathway to overcome drug resistance and inhibit multiple tumour-promoting pathways simultaneously, offering better therapeutic alternatives for patients with aggressive or advanced malignancies.
The drug ganetespib addresses oncology therapeutics for pharmaceutical developers and clinical oncologists targeting cancers such as breast, lung, gastric, and blood malignancies. Regarding readiness, it has advanced beyond preclinical evaluations and is currently in phase II clinical trials as a first-line therapy for metastatic breast cancer. Its development pathway suggests an applied clinical stage aiming at regulatory approval and integration into commercial cancer treatment regimens.
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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.
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DOI: 10.3390/ijms24055014
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