or more sentences. Understanding how these changes arise
and how they affect cellular functions is part of the field of
research called epigenetics.
Each cell in an individual contains the same 25,000 genes.
Natural differences in genome accessibility, which generate
different patterns of gene usage, lead to the diverse array
of cell types in our bodies. Special chemical marks on DNA
and histones together determine genome accessibility, and
thus gene usage, in a given cell type. The sum of these
chemical marks, called epigenetic marks, is referred to as the
Most cancer cells have profound abnormalities in their
epigenomes when compared with normal cells of the same
tissue. In many cases, these epigenetic defects work in
conjunction with permanent changes in the genetic material of
the cell to promote cancerous behaviors.
One of the most exciting discoveries is that some epigenetic
abnormalities are reversible. As a result, researchers are
exploring whether therapies that work by reversing specific
epigenetic defects can be used to treat cancer. The potential
of this concept is highlighted by the fact that there are
already four FDA-approved epigenetic drugs, which are
used to successfully treat some patients with lymphoma
or preleukemia who are nonresponsive to traditional
chemotherapy. With efforts underway to map the epigenetic
changes in all major types of cancer, it seems likely that more
epigenetic drugs are destined to benefit many more patients in
the near future and for years to come.
Over the years, researchers have determined that cancer-associated genetic mutations are most often found in one of
two classes of genes: proto-oncogenes and tumor suppressor
genes. These genes normally regulate the natural processes of
cell growth and death to keep our tissues and organs healthy.
Mutations in proto-oncogenes change them into oncogenes
that result in altered proteins that can drive the initiation and
progression of cancer. These altered proteins usually work by
over activating the normal networks that drive cell division and
survival; some can be directly targeted by precision medicines.
Tumor suppressor genes code for proteins that normally stop
the emergence of cancer by repairing damaged DNA or by
restraining signals that promote cell survival and division.
Mutations in these genes typically inactivate them and can
result in the production of dysfunctional proteins that do not
stop the accumulation of harmful mutations or that allow
overactive cells to survive, causing cancer to develop.
The understanding that cancer can be caused by genetic
changes that lead to altered proteins and disruption of normal
cell behaviors has spurred the development of cancer drugs
that target these proteins. This approach, treating cancer
patients based on the genetic and molecular profile of their
cancer, is referred to as personalized cancer medicine,
molecularly based medicine, precision medicine, or tailored
therapy. Although it is a relatively new concept, it is already
transforming the prevention, detection, diagnosis, and
treatment of cancer.
Beyond Genetics: The Role of Epigenetics
It is clear that mutations in the genome of a normal cell can
lead to cancer. However, recent research has shown that
changes in the regions of the genome available for use by a
cell also influence the development of cancer. To return to the
analogy of a book, these changes in genome accessibility alter
how the book is read; for example, creasing a page to hide one
Patterns of DNA methylation and histone acetylation, which are epigenetic marks
that control genome accessibility, are modified in many cancer cells. The FDA has
approved the DNA methylation inhibitors azacitidine (Vidaza) and decitabine (Dacogen)
for the treatment of myelodysplastic syndrome. Likewise, the histone deacetylase
inhibitors romidepsin (Istodax) and vorinostat (Zolinza) are FDA-approved for the
treatment of certain lymphomas.