Mary is a 46-year-old mother of two daughters, ages 17
and 19. Eight years ago she was diagnosed with breast
cancer, and after a conventional course of chemotherapy
followed by radiation, the cancer was driven into remission.
Lately she is having increasingly severe back pains. At a
routine check-up, she mentions the pains to her surgeon, who
performs a bone scan. The scan reveals several "hot
spots," regions of increased metabolic activity in her
spinal column. The diagnosis made on a biopsy of one of
these hot spots catches her completely off guard: metastasis
of her breast cancer.
Patients like Mary
inevitably ask the question: Why me? But for those of us who
study what cancer is, its development and spread, the
question is rather: Why at all?
The simple answer is that in cancer the genes and
chromosomes of cells become disorganized, leading them to
enact genetic programs far different from the intended
normal program. It has often been noted that cancer cells
are unusual because they are undifferentiated; that is, they
lose functions and, as a result, fail to fully develop the
characteristics and proper activities of mature cells of
their type. Quite remarkably, metastatic cancer cells gain
new functions, taking on characteristics unrelated to the
normal, often sedentary cell type.
Most cells are
designed to remain fixed in their organs in order to perform
the specialized activities for which they are particularly
adapted. They are held tightly in place by molecular tethers
that link them with the other cells and the proteinaceous
matrix in that tissue. Clearly, these cells are not meant to
roam around the body and take up residence in other organs.
Metastatic cancer cells are altered in such a way that they
can break those bonds. Further cellular remodeling allows
metastatic cells to chew through the proteinaceous walls
that line tissues and blood vessels and quite literally walk
away from their parent organ to invade other tissues and
organs.
If it were not so potentially damaging,
metastasis might be just an interesting cellular oddity. But
the fact is that the metastatic tumor is often more
dangerous than the original, or primary, tumor. Metastatic
cancer cells crowd out normal cells in the tissue and
deprive them of nutrients. In effect, the metastatic cells
starve and displace functional cells. This can be lethal
when the organ—or organs, since cancer cells can go
almost anywhere and often end up in several new
organs—can no longer perform its vital functions.
Over the past few decades, biologists have become ever
more precise in determining the genetic, biochemical and
cellular changes that drive a cell first to become cancerous
and then to become metastatic. And new discoveries are being
reported daily. So, although not all of the details are
entirely known, a comprehensive picture of these alterations
is emerging. Each new piece of information not only
contributes to this overall picture; it also provides a site
of potential therapeutic intervention to inhibit the
progression of cancer—if not, someday, to eliminate it
entirely.