After my wife Helen was diagnosed with cancer about 15 years
ago, I found myself obsessively reading clinical and other literature about the
disease. I was trying to fathom
what had befallen her, to understand what the doctors were saying, and to see
if I could divine any courses of action that they may have ignored, including
unconventional medicine. By the
time she died a year and a half later, after three operations and a course of
chemotherapy, I'd concluded that no one, experts included, had a fundamental
understanding of the root causes of the disease. While effective therapies had been developed over the
years, they seemed to have been derived through a helter-skelter process,
mostly trial and error. I couldn't
perceive a coherent scientific theory underpinning oncology at the level, say,
of our knowledge of how the immune system works.
It turns out that I was both right and wrong: mostly right about
the status of clinical oncology at the turn of the century, wrong about the
status of oncological science, whose fruits were then rapidly multiplying in
research labs but had not yet entered clinical use. An excellent book chosen by my book club has brought me up
to date: The
Emperor of All Maladies: A Biography of Cancer by Siddhartha
Mukherjee. It's a
page-turner that deserves the Pulitzer Prize it won. Mukherjee, a clinical and research oconologist with a
splendid gift for writing, takes the reader from the earliest surviving written
description of cancer (Egypt, 2500 BCE) through the present, using a mixture of
historical cameos, personal clinical reminiscences, and science writing for the
layperson.
Most of the book is of necessity devoted to the past century
or so, when "modern" methods have been employed in fighting
cancer. As Mukherjee describes the
situation, the three regimes of medical treatment—surgery, radiation and
chemotherapy—developed largely in isolation from one another, with each set of
practitioners unwarrantedly convinced that their own techniques would
ultimately lead to a "universal cure" for a disease of infinite variety. For many years, they took sometimes extreme paths in
desperate attempts to achieve that end.
For example, many surgeons by the mid-twentieth century
would attack breast cancer by excisions of not only the breast but also the
pectoral muscles, the axillary nodes, the chest wall and occasionally the ribs,
parts of the sternum, the clavicle and the lymph nodes inside the chest,
leaving the patient grossly maimed.
Similar excesses were devised by chemotherapists, who used megadoses of
cocktails of ever more poisonous cytotoxins, which massively killed both
cancerous and healthy cells indiscriminately, bringing patients to the verge of
death, or even killing them. Such
drastic measures were later shown to have no benefits beyond regimens of much
more limited scope, to which treatments reverted.
By the last decades of the twentieth century, although
preventive measures like the campaign against smoking and the widespread use of
screening to detect tumors at early stages were still yielding increasing
benefits, the standard regimes of surgery, radiation and chemotherapy were
encountering diminishing returns. A
more scientific and methodical oncology was needed to discover additional forms
of treatment. Fortunately,
advances in genomics provided the basis for such a new approach, by explaining
why cells can suddenly engage in runaway division rather than normal mitosis.
A normal cell has genes that turn on when necessary to allow
mitosis to occur, then turn off, stopping further cell division. Such genes can become mutated into
"oncogenes" by an environmental factor or an error in DNA
transcription, with the result that they are no longer able to turn off,
potentially allowing the cell to divide beyond control into tumors. Other genes, called
"anti-oncogenes," are control genes, programmed so that they normally
will suppress oncogene-driven, runaway cell division. When anti-oncogenes themselves suffer mutations, however,
they can lose this capability. It
normally takes a "pathway" of mutations of several different
proto-oncogenes and anti-oncogenes in a cell, over several years, before that
cell finally becomes fully tumorous.
A large number of proto-oncogenes and anti-oncogenes have
already been identified, and efforts have started on construction of a
compendium of all such genes and an "atlas" of where they are
typically located on the genome for various types of cancer. The latter effort is complicated by the
fact that apparently similar cancers in different people may have different
maps of mutated genes.
The great hope for the new scientific oncology, only
minimally fulfilled thus far, is that after identifying which genes in a
cancerous cell's genome are the culprits, specific directed agents that
incapacitate just those genes can be applied, eliminating cancer cells but not
healthy cells. (This would be more
akin to antibiotics directed against specific bacteria than to traditional
chemotherapy, which kills cells unselectively.) Some therapeutic drugs that disable specific cancer genes
have indeed already been identified, and hopefully a full pharmacopeia of such
drugs can be developed, each capable of attacking one or more cancer
genes.
Substantial progress has been made. In the past few years, comparison of
the faulty genome of a cancer cell with the healthy genome of a normal cell
from the same person has been achieved, in an attempt to identify the mutant
genes that are responsible for the tumor.
(Generally, only a small subset of mutant genes are cancer-related,
since other genes can also mutate as a tumor cell continues to divide.) Then, if appropriate agents that
incapacitate the cancer genes are known, they have been used. So far only limited success has been
achieved—the cancers, temporarily suppressed but ever wily, have regenerated
themselves. Perhaps it is the old
problem that can occur with traditional treatments, of a few cells surviving
the onslaught. Perhaps a tumor has
more than one type of cancerous cell in it. Perhaps not all the cancer genes were detected. Much more research clearly needs to be
done.
None the less, it seems to me, even as a layman, that
oncology is now on the right track. A rationally conceived, methodical plan, based
on good science, is under way.
With any luck, many—maybe most—cancers will become fully curable over the
next several decades, without the harmful side effects that many cancer therapies
now have. If that happened, it
would truly be a millennial accomplishment of medical science, equivalent to the
conquest of contagious diseases.