Epigenetics Drives Pharma Innovation

Therapeutics targeting epigenetic mechanisms of disease will change the pharmaceutical marketplace.
Jan 01, 2013
Volume 26, Issue 1

K. John Morrow, Jr., PhD
In the past two decades, epigenetics has grown from an obscure concept applicable mainly to X chromosomal inactivation to one of the dominant driving forces in pharmaceutical R&D (1). Briefly stated, the epigenetic model of regulatory control is based on the observation that half of the structural genes of higher organisms are preceded by CpG islands, clusters of cytosines alternating with guanadines that constitute signaling points that respond to epigenetic signals (2). Modification of these sites through a methylation reaction blocks the transcription of linked genes. Whereas numerous pathological conditions demonstrate an epigenetic connection, progress has been most notable in the field of cancer biology.

Evidence linking epigenetic modi-fications to the activation of oncogenes or the inactivation of onco-suppressor genes is rapidly coalescing (3). Researchers currently propose a dynamically interactive model by which the genome and epigenome feed back on one another, driving the growth or the involution of tumors (4–6).

This complex model of regulatory control offers many opportunities for a more nuanced understanding of the cancer cell and how it spans the transformation from normal to various stages of malignancy. The new knowledge base opens up possibilities for early diagnosis, because subclinical tumors may release DNA molecules into the circulation that bear highly specific epigenetic modifications defining the type and stage of malignancy of a particular tumor type. These markers can be methylated sites in target genes, and as such, provide a specific and sensitive target. Currently, numerous diagnostic tests for these markers are under development (7).

By the same token, an epigenetic-based therapeutic attack on cancer has been launched. There are a number of basic science teams working with industry to define new epitherapeutics for a range of different cancers.

These changes, affecting both the diagnostic and the therapeutic aspects of oncology, demand a restructuring of our strategies for attacking this disease. There is much interest in other diseases that may have an epigenetic basis, but cancer-based investigation is far advanced over other diseases, so for the next few years this will no doubt be the prime focus of epi-drug development.

New targets call for new strategies for synthesis and production. This may influence the relative balance between small molecules and biological drugs, decisions that will affect the allocation of resources for large-scale production in the coming years. Companies have made decisions in the past reflecting their projected bioprocessing needs, with serious implications for cash flow, so it is crucial that these allocations be assigned on the basis of the best information available.

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