Merkel cell carcinoma is a rare and aggressive skin cancer. As it begins, a painless red or blue lump in the skin forms, and then metastasizes quickly. After metastasis, patients have a terrible prognosis, with only an 18% survival rate after five years. Moreover, the incidence of this malignant carcinoma is increasing.
Currently, few therapies are available for metastatic Merkel cell carcinoma. Fortunately, immunotherapies have recently been approved as treatment, but unfortunately, most patients eventually develop resistance.
Enzyme Inhibition Tactic
Because this cancer is so difficult to treat, a team of cancer researchers in California became interested in targeting Aurora kinase A to attempt to treat this cancer. Aurora kinase A is an enzyme needed for cell proliferation, and is overexpressed in many types of cancer. In theory, by inhibiting this enzyme, the growth of the cancer will be repressed. For this reason, an inhibitor specific to Aurora kinase A , LY3295668, has recently been developed. Therefore, the researchers decided to test the effectiveness of LY3295668 against Merkel cell carcinoma in cell culture.
Cell and Animal Testing
The first test involved the application of LY3295668 to Merkel cell carcinoma cell lines. The result was that Ly3295668 inhibited the cell growth and raised levels of biomarkers of cell cycle arrest and apoptosis. Then to investigate further, mice bearing Merkel cell carcinoma tumors were created. In these mice, after treatment with LY3295668, the tumors shrank. However, when the researchers stopped LY3295668 treatment, the tumors grew again and were resistant to further LY3295668 treatment.
Insufficient Results
These results suggest that LY3295668 has the potential to treat this type of carcinoma, but that this cancer can develop resistance to this drug quickly. As noted, this chemical does show effectiveness against the cancer, however, the overall result is rather insufficient. In consequence, if LY3295668 is to be developed into a clinical treatment, it will in all likelihood need to be used in combination with other drugs.
Das B, Kannan A, Nguyen Q, et al. Selective inhibition of aurora kinase A by AK-01/LY3295668 attenuates MCC tumor growth by inducing MCC cell cycle arrest and apoptosis. Cancers (Basel). 2021 Aug;13(15):3708. doi:10.3390/cancers13153708. PMID: 34359608.