Dissecting tumorigenic mechanisms and identification of candidates for targeted therapies against cancer

The persistence of the inflammatory states of chronic diseases that cause constant damages to liver cells to can lead to tumor development. Liver carcinogenesis is a multistep process in which cells accumulate genetic and epigenetic alterations that lead to an uncontrolled proliferation. Indeed, proliferation, the resistance to inhibitory stimuli, angiogenesis (the formation of new blood vessels), and infinite replication are some of the cancer hallmarks. All these mechanisms derive from several molecular alterations. For example, during carcinogenesis cells re-activate the Telomerase reverse transcriptase, an enzyme that is essential the telomeres (the chromosomal extremities) length maintenance. The normal hepatocytes do not express telomerase and the telomere shortening results in a biological process named senescence. Senescent cells undergo to programmed death when telomeres become critically short. With the reactivation of telomerase in cancer the telomere shortening is prevented and cells can proliferate indefinitely. Aurora Kinase A is another enzyme important for cell proliferation since it is involved in replication. Aurora Kinase A is also involved in the “DNA damage response” pathway that triggers cell death in case of severe DNA damage. Cancer cells have a certain degree of tolerance towards these stimuli and are able to proliferate even in presence of some DNA damage.