- What are targeted cancer therapies?
Targeted cancer therapies use drugs that block the growth and spread of cancer.
They interfere with specific molecules involved in carcinogenesis (the process
by which normal cells become cancer cells) and tumor growth. Because scientists
call these molecules “molecular targets,” these therapies are
sometimes called “molecular-targeted drugs,” “molecularly
targeted therapies,” or other similar names. By focusing on molecular
and cellular changes that are specific to cancer, targeted cancer therapies
may be more effective than current treatments and less harmful to normal cells.
Most targeted cancer therapies are in preclinical testing (research with
animals), but some are in clinical
trials (research studies) or have been approved by the U.S. Food and Drug
Administration (FDA). Targeted cancer therapies are being studied for use
alone, in combination with each other, and in combination with other cancer
treatments, such as chemotherapy.
- What are some of the cellular changes that lead to cancer?
Normally, cells grow and divide to form new cells as the body needs them.
When cells grow old, they die, and new cells take their place. Sometimes this
orderly process goes wrong. New cells form when the body does not need them,
and old cells do not die when they should. These extra cells can form a mass
of tissue
called a growth or tumor. The cells in malignant
(cancerous) tumors are abnormal
and divide without control or order. They can invade and damage nearby tissues
and organs.
Also, cancer cells can break away from a malignant tumor and spread to other
parts of the body.
Normal cell growth and division are largely under the control of a network
of chemical and molecular signals that give instructions to cells. Genetic
alterations
(changes) can disrupt the signaling process so that cells no longer grow and
divide normally, or no longer die when they should. Alterations in two types
of genes
can contribute to the cancer process. Proto-oncogenes are normal genes that
are involved in cell growth and division. Changes in these genes lead to the
development of oncogenes,
which can promote or allow excessive and continuous cell growth and division.
Tumor
suppressor genes are normal genes that slow down cell growth and
division. When a tumor suppressor gene does not work properly, cells may be
unable to stop growing and dividing, which leads to tumor growth.
To use the metaphor of a car, the presence of an oncogene is like having
a gas pedal that is stuck to the floorboard, causing cells to continually
grow and divide. Tumor suppressor genes act like a brake pedal. The loss of
a functioning tumor suppressor gene is like having a brake pedal that does
not work properly, allowing cells to continually grow and divide.
Genetic changes that are not corrected by the cell can lead to the production
of abnormal proteins.
Normally, proteins interact with each other as a kind of relay team to carry
out the work of the cell. For example, when molecules called growth
factors (GFs) attach to their corresponding growth factor receptors
(GFRs) on the surface of the cell, a process carried out by proteins signals
the cell to divide. Damaged proteins may not respond to normal signals, may
over-respond to normal signals, or otherwise fail to carry out their normal
functions. Cancer develops when abnormal proteins inside a cell cause it to
reproduce excessively and allow that cell to live longer than normal cells.
- How do targeted cancer therapies work?
Targeted cancer therapies interfere with cancer cell growth and division
in different ways and at various points during the development, growth, and
spread of cancer. Many of these therapies focus on proteins that are involved
in the signaling process. By blocking the signals that tell cancer cells to
grow and divide uncontrollably, targeted cancer therapies can help to stop
the growth and division of cancer cells.
- What are some types of targeted cancer therapies?
Targeted cancer therapies include several types of drugs. Some examples are
listed below:
- “Small-molecule” drugs block specific enzymes
and GFRs involved in cancer cell growth. These drugs are also called signal-transduction
inhibitors. Gleevec®
(STI–571 or imatinib mesylate) is a small-molecule drug approved by
the FDA to treat gastrointestinal
stromal tumor (a rare cancer of the gastrointestinal
tract) and certain kinds of chronic
myeloid leukemia (1, 2). Gleevec targets abnormal proteins, or enzymes,
that form inside cancer cells and stimulate uncontrolled growth. Iressa®
(ZD1839 or gefitinib)
is approved by the FDA to treat advanced non-small
cell lung cancer. This drug targets the epidermal
growth factor receptor (EGFR),
which is overproduced by many types of cancer cells. Other small-molecule
drugs are being studied in clinical trials in the United States.
- “Apoptosis-inducing” drugs cause cancer cells to undergo apoptosis
(cell death) by interfering with proteins involved in the process. Velcade®
(bortezomib)
is approved by the FDA to treat multiple
myeloma that has not responded to other treatments (3). Velcade causes
cancer cells to die by blocking enzymes called proteasomes, which help to
regulate cell function and growth. Another apoptosis-inducing drug called
Genasense™ (oblimersen),
which is only available in clinical trials, is being studied to treat leukemia,
non-Hodgkin lymphoma,
and solid
tumors. Genasense blocks the production of a protein known as BCL–2,
which promotes the survival of tumor cells. By blocking BCL–2, Genasense
leaves the cancer cells more vulnerable to anticancer drugs.
- Monoclonal antibodies, cancer
vaccines, angiogenesis
inhibitors, and gene
therapy are considered by some to be targeted therapies because they
interfere with the growth of cancer cells. Information about these treatments
can be found in the following National Cancer Institute (NCI) fact sheets,
which are available on the Internet or by calling the Cancer Information
Service (CIS) (see below):
—Biological Therapies for Cancer: Questions and Answers
includes information about monoclonal antibodies and cancer vaccines.
This fact sheet is available at http://www.cancer.gov/cancertopics/factsheet/Therapy/biological
on the Internet.
—Herceptin® (Trastuzumab): Questions and Answers contains
information about Herceptin, which is a monoclonal antibody. This fact
sheet can be found at http://www.cancer.gov/cancertopics/factsheet/Therapy/herceptin
on the Internet.
—Angiogenesis Inhibitors Therapy: Questions and Answers
is available at http://www.cancer.gov/cancertopics/factsheet/Therapy/angiogenesis-inhibitors
on the Internet.
—Gene Therapy for Cancer: Questions and Answers can be
found at http://www.cancer.gov/cancertopics/factsheet/Therapy/gene
on the Internet.
- What impact will targeted therapies have on cancer treatment?
Targeted cancer therapies will give doctors a better way to tailor cancer
treatment. Eventually, treatments may be individualized based on the unique
set of molecular targets produced by the patient's tumor. Targeted cancer
therapies also hold the promise of being more selective, thus harming fewer
normal cells, reducing side
effects, and improving the quality
of life.
- What are some resources for more information?
The NCI's Molecular Targets Development Program (MTDP) is working to identify
and evaluate molecular targets that may be candidates for drug development.
As part of the NCI's Center for Cancer Research, the MTDP provides research
support for NCI-designated, high-priority drug discovery, development, and
research focused on specific molecular targets, pathways, or processes. The
MTDP's Web site is http://home.ncifcrf.gov/mtdp/
on the Internet.
Information about clinical trials is available from the CIS (see below).
Information specialists at the CIS use PDQ®,
the NCI's cancer information database, to identify and provide detailed information
about specific ongoing clinical trials. PDQ includes all NCI-funded clinical
trials and some studies conducted by independent investigators at hospitals
and medical centers in the United States and other countries around the world.
People also have the option of searching for clinical trials on their own.
The clinical trials page of the NCI's Web site, located at http://www.cancer.gov/clinicaltrials/
on the Internet, provides information about clinical trials and links to PDQ.