The gene BIRC5 is an “important player” in chondrosarcoma survival, say researchers from Leiden University, The Netherlands, and Athens University, Greece. They propose that targeting survivin, a protein encoded by BIRC5, could lead to a potential avenue for treating the tumor that accounts for 20% of all malignant bone cancers.
Chondrosarcomas are “intrinsically resistant” to chemo- and radiotherapy,” the researchers say, leaving surgery as the only curative option. So they aimed to identify genes that could be used in targeted drug treatment.
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They screened for 51 apoptosis-related genes. When the screening pinpointed survivin as essential for chondrosarcoma survival, the researchers used immunohistochemistry to analyze cytoplasmic survivin expression in 207 chondrosarcomas of different subtypes. Survivin is highly expressed, they found, in tumor tissue and cell lines of conventional as well as rare subtypes of chondrosarcoma.
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The researchers also tested sensitivity to YM155 (a survivin-inhibiting compound) and found chondrosarcoma cells lines were highly sensitive. They say their findings suggest that YM155, which is already in phase I and II clinical trials for other tumors, could be readily applicable in clinical trials for chondrosarcoma patients. Although some larger phase II studies have not shown promising antitumor activity in diffuse large B-cell lymphoma, non-small cell lung cancer, melanoma, or prostate cancer, that doesn’t mean YM155 can’t help in chondrosarcoma patients, they say. Especially, they note, because in chondrosarcoma,YM155 does not induce apoptosis but blocks the cell cycle.
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In particular TP53 mutant cell lines were sensitive; thus, TP53 mutation may be a biomarker that can allow preselecting patients for treatment.
Source:
de Jong Y, van Oosterwijk JG, Kruisselbrink AB. Targeting survivin as a potential new treatment for chondrosarcoma of bone. Oncogenesis. 2016;5:e222.
doi: 10.1038/oncsis.2016.33.
