LINCURE · Harness lncRNA targeting to treat colorectal cancer

Colorectal cancer (CRC) is the third leading cause of cancer-related death globally. Despite the therapeutic advances, innate and acquired resistance is still an adversity that needs to be overcome. Therefore, there is an urgent need to identify more targeted and specific therapeutic approaches in order to increase success of the treatment and reduce the medical and economic burden of therapeutic failures. Numerous studies have been conducted to target the replication stress response, a hallmark of cancer and drug resistance, in cancer therapy. However, hitting this essential pathway can trigger deleterious and non-specific cellular responses. Our research introduces a novel perspective to this problem by focusing on the RNA components of the replication stress pathway. lncRNAs are untranslated RNAs whose emerging role in regulating gene expression has changed the way we look at genes and their functions. lncRNAs play a regulatory role in mechanisms of acquired tumour drug resistance. Moreover, their rapid turnover, tissue and pathology specificity make them ideal targets for effective therapeutic avenues that don’t bare the same toxicity as conventional approaches. Our dedicated ERC research has unveiled a lncRNA with remarkable biological properties. CRC cells subjected to replicative stress are addicted to its expression, representing a highly promising therapeutic target. Building on these novel findings, we propose LINCURE, a new therapy based on the inhibition of this lncRNA. lncRNA inhibitors will be used alone or in combination with the conventional 5-FU therapy to reach therapeutic efficacy for drug resistant CRC. We will integrate our unique knowledge with recent advancements in the successful development of delivery methods for RNA-based therapies, which have generated a surge of optimism in the realm of RNA therapeutics. The objective is to start a promising pathway toward translating our findings into effective clinical therapies.