Alternative to Paclitaxel Under Study in Ovarian and Uterine Cancers
Posted: Tuesday, October 2, 2018
Resistance to paclitaxel and related microtubule inhibitors is common in women with high-grade ovarian or uterine cancer, driving researchers to focus on identifying new chemotherapy agents. A preclinical study has revealed that SQ1274, a novel microtubule inhibitor, appears to be a “viable alternative to paclitaxel” in this patient population. Kathryn A. Mills, MD, of Washington University School of Medicine, St. Louis, and colleagues published their findings in Gynecologic Oncology.
Rather than binding to the taxane-binding site on microtubule polymers like paclitaxel, SQ1274 binds to the colchicine-binding site on tubulin and destabilizes microtubules. Studies have shown that cancer cells are less susceptible to developing resistance to colchicine and colchicine derivatives than to other microtubule inhibitors.
Using assays, Dr. Mills and colleagues assessed the sensitivity of ovarian and uterine cancer cell lines to SQ1274 and paclitaxel. The half maximal inhibitory concentration (IC50) values for SQ1274 were 7.7- and 12.2-fold lower than the IC50 values for paclitaxel in ovarian and uterine cells, respectively, indicating a higher level of potency for SQ1274 versus paclitaxel. The researchers also found that SQ1274 causes increased cell-cycle arrest and apoptosis compared with paclitaxel, possibly by decreasing RNA and AXL protein expression. As for in vivo activity, SQ1274 more effectively inhibited tumor growth in mouse models compared with paclitaxel, the study found.
“These preclinical observations, in combination with previous studies of SQ1274, strongly support its further development as a therapeutic alternative to paclitaxel for both ovarian and uterine serous cancers,” concluded the investigators.