Combined Use of a SERCA Inhibitor and a Calmodulin Antagonist
SEC62 is a new candidate oncogene showing a significant overexpression and elevated protein content in cancer of the lung and prostate. Elevated Sec62 protein content has been shown to be functionally linked to increased cell migration capability and to reduced sensitivity to Thapsigargin-induced ER stress, both of which are crucially regulated by the cytosolic and ER luminal calcium concentration. Therefore there is the need of a pharmaceutical treatment that is able to treat SEC62 overexpressing tumor both
- by inhibiting the cell migration mechanism favored by the overproduction of Sec62 protein and
- by counteracting the effect that the Sec62 protein overproduction has in reducing the effect of SERCA inhibitors as used in the treatment of tumor.
Scientists of Saarland University found that the administration of a Calmodulin antagonist such as Trifluoperazine in combination with a SERCA inhibitor like Thapsigargin is surprisingly useful in the treatment of tumors, which are in particular characterized by the overexpression of the SEC62 gene/Sec62 protein. They showed that the combined use of a SERCA inhibitor and a Calmodulin antagonist acts
- on the inhibition of cell migration and
- counteracts the reduced efficiency of SERCA inhibitor observed in the treatment of tumors overexpressing SEC62 gene /protein, thereby providing an effective treatment of these tumors.
Notably, the Calmodulin antagonist Trifluoperazine is an approved antipsychotic und antiemetic drug.
Treatment of tumors with SEC62 overexpression as found in non small cell lung carcinoma (97%), lung adenocarcinoma (86%) and prostate carcinoma (50%).
- The combined use of a SERCA inhibitor and a Calmodulin antagonist outmatches the sole treatment with SERCA-inhibitors such as Thapsigargin analogues
- The combined use of a SERCA inhibitor and a Calmodulin antagonist enhances the sensitivity of the tumor for treatment with SERCA-inhibitors in Sec 62 overproducing tumors
- Reduced SERCA-inhibitor administration and thereby reduction of adverse effects
- Detection of SEC62 overexpression could guide personalized therapeutic strategies