Jaroslav Truksa

• Mission: Identify molecular targets that are essential for all cancer cells including those resistant to currently used treatment.
• Vision: Even the cancer cells have their vulnerabilities that should be identified and utilized, one of them being their dependency on iron.

We focus on the molecular mechanisms of cancer cell resistance and on targeting iron metabolism of cancer cells with mitochondrially targeted iron chelators. Finding novel targets responsible for cancer cell resistance to therapy, as well as identifying and targeting key metabolic pathways in cancer cells, is essential for treatment as well as diagnosis and prognosis of the disease.

Breast cancer is the most common cancer in women worldwide. In the estrogen-positive subtype of this cancer, the standard treatment is the administration of tamoxifen. This treatment is effective and well tolerated, yet, unfortunately, a significant proportion of patients eventually become insensitive to treatment and relapse and metastasis of the disease occurs. Our laboratory has documented a link between tamoxifen resistance and mitochondrial function and biology that has not yet been described. We have shown that tamoxifen-resistant cells have fragmented mitochondria that are less respiratory and contain elevated levels of superoxide, and their metabolism is more glycolytic. We also show that tamoxifen-resistant cells have deregulated lipid metabolism and increased level of the mitochondrial histone deacetylase, sirtuin 3. Confirmation of the link between mitochondria and tamoxifen resistance was then provided by the finding that cells with non-functional mitochondria, the so-called rho zero cells, exhibit strong resistance to tamoxifen.