Calcium channel linked to cancer drug resistance
Chemotherapy tumor resistance develops after long-term regimens of the platinum-containing anticancer drug carboplatin. Scientists have observed an enlarged cell morphology and involvement of T-type calcium channels in resistant ovarian cancer cells. Sooyun Kim and researchers at Seoul National University wanted to find out if these characteristics also relate to carboplatin resistance seen in retinoblastoma, an aggressive childhood cancer. They published their findings in a recent Journal of Biological Chemistry article.

Immunofluorescence staining and pharmacological inhibition experiments identified the Cav3.3 channel as the overexpressed calcium channel subtype that contributes to the sustained currents. The authors further showed that messenger RNA expression levels only for Cav3.3 increased after carboplatin exposure, while the levels for the other Cav3.1 and Cav3.2 subtypes slightly decreased in the resistant cells relative to the original retinoblastoma strain.
Finally, the researchers determined that treating the resistant retinoblastoma giant cells with a Cav3.3 inhibitor increased their sensitivity to carboplatin. They only observed this increase in carboplatin sensitivity in the resistant cells and not in the original retinoblastoma strain, indicating that Cav3.3 plays a specific role in drug resistance.
Cav3.3 could potentially be a target for the treatment of carboplatin-resistant retinoblastoma. Future experiments will help identify additional proteins and pathways that may connect Cav3.3 to chemotherapeutic resistance in retinoblastoma and whether the involvement of Cav3.3 over the other channel subtypes is observed in other cancers.
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