Lucia Altucci

In recent years, the study of anticancer bioactive compounds from marine sources has received wide interest. Contextually, world regulatory authorities have approved several marine molecules, and new synthetic derivatives have also been synthesized and structurally improved for the treatment of numerous forms of cancer. However, the administration of drugs in cancer patients requires careful evaluation since their interaction with individual biological macromolecules, such as proteins or nucleic acids, determines variable downstream effects. This is reflected in a constant search for personalized therapies that lay the foundations of modern medicine. The new knowledge acquired on cancer mechanisms has certainly allowed advancements in tumor prevention, but unfortunately, due to the huge complexity and heterogeneity of cancer, we are still looking for a definitive therapy and clinical approaches. In this review, we discuss the significance of recently approved molecules originating from the marine environment, starting from their organism of origin to their structure and mechanism of action. Subsequently, these bio-compounds are used as models to illustrate possible bioinformatics approaches for the search of new targets that are useful for improving the knowledge on anticancer therapies.

Chromatin has an extremely flexible structure that allows the fine regulation of gene expression. To orchestrate this process, small chemical modifications are dynamically added or removed on DNA, RNA and histone substrates. Epigenetic modifications govern a plethora of key cellular functions, whose dysregulation contributes to oncogenesis. The interrelationship between (irreversible) genetic mutations and (reversible) epigenetic alterations and how this crosstalk regulates gene expression has long been a major area of interest. Marks modulating the RNA code (epitranscriptome), such as the well‐studied N 6 ‐methyladenosine (m 6 A), are known to influence stability, metabolism and life cycle of many mRNAs, including cancer‐associated transcripts. Together, epigenetic and epitranscriptomic pathways therefore control the entire cellular expression profile and, eventually, cell fate. Recently, previously undescribed crosstalk between these two pathways has started to be unrevealed. For example, m 6 A and its effectors cooperate with histone modifications to localize chromatin‐modifying complexes to their target regions. Epigenetic marks governing the expression of m 6 A factors can also be found at specific genetic loci. m 6 A itself can mark noncoding RNAs (including lncRNAs, circRNAs and miRNAs), influencing their structure, maturation and function. These interactions affect both cell physiology and pathology. Clear evidence that dysregulation of this network plays a role in cancer has emerged, suggesting a new layer of complexity in the landscape of gene expression. Here, we summarize current knowledge on the interplay between m 6 A epitranscriptome and epigenome, focusing on cancer processes. We also discuss strategies to target m 6 A machinery for future therapeutic intervention.