NEW EPIGENETIC ANTICANCER DRUGS
Table I: FDA-approved epigenetic anticancer agents.
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In addition to the four drugs that have already been approved by FDA (see Table I), a number of new compounds are in clinical trials. Although they are a miniscule component of the current anticancer drug
market, their usage is expanding. Cai et al. (2012) have summarized those compounds under scrutiny for use in the treatment
of breast cancer (8).
Until recently, epigenetic changes had not been recognized as playing a significant role in the origin and progression of
cancers. This lack of attention is changing rapidly, as a wealth of research findings are appearing, documenting epigenetic
variation and its role in many disease processes. The dominant paradigm, however, has been based on the concept that alterations
in DNA base pair sequences are responsible for practically all the variability observed in normal and pathological expression
in humans and other living forms.
But the new concept of the origins of cancer is more complete, and proposes an interplay between epigenetic and genetic changes.
Baylin and Jones have summarized the history of this movement over the last decade, and they note that there is an emerging
view of what has come to be called "the cancer epigenome" (9). The cancer epigenome is essentially a wide collection of abnormalities
based on somatically heritable alterations that are not due to primary DNA sequence changes. In fact, the genesis and progression
of tumors appears to be a complex process in which DNA-based alterations can favor the development of epigenetic changes,
which increase the malignant status of a particular cancer.
The additional layers of complexity introduced by findings in epigenetics are highlighted by Tessema et al., who state that
in the past, the main focus was on the damage to the DNA caused by cigarette smoking, but now there is a major concern that
epigenetic control molecules may be as important a cause of cancer (10). This more complex mechanism means that an interactive
picture will need to be developed which takes into account the feedback between carcinogenic changes in the genome reflecting
back to the epigenome, and vice-versa.
The extent of epigenetic damage in cancerous tissue is startling. For example, epigenetic molecules are affected in 60% of
patients with pancreatic neuroendocrine tumors. Other molecules are abnormal in 41% of cases of kidney cancer. The aim with
epigenetic drugs is to revert those bar codes back to normal, according to Jonathan M. Yingling, vice-president for cancer
research at Eli Lilly (11).
EPIGENETICS AND THE BIOPROCESSING INDUSTRY
The epigenetics revolution has arrived at an opportune moment, in which old business models are under siege, and there is
an aggressive reassessment taking place within the pharmaceutial industry (12). For years, Big Pharma R&D pursued blockbuster
drugs that targeted chronic, widespread conditions requiring pharmaceutical agents to be taken over an extended and indefinite
period. Lipitor was the all-time poster child of this strategy, and brought in $70 billion in sales for Pfizer over the course
of its patent lifetime. Numerous other drugs developed for the treatment of allergies, high blood pressure, and sexual dysfunction
were extremely successful in the marketplace. This model has received a drubbing as year after year R&D costs rose and productivity
dropped.
But the rise of epigenetics has introduced a new variable into the equation. All the major pharma companies have epigenetics
divisions in place, and some latecomers may not be able to catch up with competitors such as Merck and Novartis. And while
the focus is currently on oncology-based drugs, evidence is emerging that many psychiatric disorders have a strong epigenetic
contribution (13).
Currently, epigenetics-based drugs are small slice of the large pharma pie. However there are a number of epigenetically targeted
compounds in clinical trials, all oncology-based. It is noteworthy that they are all small molecules that will not call for
bioprocessing facilities. The global market for one biologic product, monoclonal antibodies, was $44.6 billion in 2011, predicted
to grow to $58 billion by 2016. In 2011, epigenetic drug sales were only around $1 billion, but some analysts predict that
their growth rate in sales will be much higher, 80 to 100% annualized growth (14).
Of course such predictions come with many caveats, and many factors can intervene in the coming years. The most crucial unknowable
is how successful advances in epigenetics research will be in the near future. However, making reasoned assumptions concerning
the transformations of the industry driven by the epigenetics revolution, the bioprocessing industry should be prepared to
participate in a smaller percentage of the overall oncology drug market.
K. John Morrow, Jr., PhD, is head of Newport Biotechnology Consultants and a member of BioPharm International's editorial advisory board , kjohnmorrowjr@insightbb.com
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