Kanduri, Chandrasekhar – Long non-coding RNA molecules: Studies of their function and therapeutic applications.

Background

The development of new cancer treatments, e.g. Immunotherapies have been very successful in recent times. However, many patients with advanced cancer do not respond to these treatments. Lung cancer is an example where about 70% of patients do not respond to immunotherapy. Neuroblastoma, a childhood cancer, is another example, where 50% of the high-risk forms cannot be cured with current treatment methods. It is thus obvious that cancer must be treated in a completely new way. In this project, we will study a new type of molecule, ‘non-coding RNA’ (lncRNA), which has recently been shown to be strongly associated with cancer – some propellant, others protective.

Description

We have recently identified several embryonally expressed lncRNAs that are not produced in healthy adult tissue but are found in cancer cells. We believe that these lncRNAs are harmful, and we want to develop treatments that can block their effect. In another part of the project, we have also identified cancer-driving cell cycle-specific lncRNA. We now want to investigate whether blocking these lncRNAs can be used to cure cancers that no longer respond to chemotherapy. Impaired cell differentiation is an important characteristic of cancer, and we want to find out how loss of protective lncRNA associated with cell differentiation causes neuroblastoma.

Goal

Our development of therapeutic oligonucleotides that inhibit the function of tumor-driving embryonic and cell cycle-specific lncRNAs in cancer cells may lead to less toxic and more specific cancer treatments. In the longer term, this will facilitate the establishment of lncRNA-based precision medicine. If we understand how cell differentiation-specific lncRNA protects against cancer, we can also develop a completely new type of cancer treatment – inhibition of incorrectly activated signaling pathways that lead to the development of cancer cells.

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