Before Treatment: Making Sense of Cancer Therapies

Scientists continue to learn more about cancer’s biology and how it affects each patient. As they make new discoveries, they are able to refine existing treatments and develop new ones.

SURGERY

If the cancer has not spread, surgery may be used to remove the tumor and, depending on the pathology of the cancer, the surrounding tissue. In some cases, patients may be eligible for less invasive surgical options.

Types of Cancer Surgery:

Laparoscopic surgery requires one or more small incisions that allow a thin fiberoptic scope, called a laparoscope, and specially designed surgical instruments to be inserted into the body to remove the tumor. Disease-free survival and recurrence rates for many types of cancer seem to be about the same when laparoscopic surgery is compared with traditional open surgery but for very specific tumor types and situations. The main benefits are faster recovery times, shorter hospital stays and fewer complications.

Robotic surgery may have even more benefits for some patients. As with laparoscopic surgery, the operation requires a few small incisions. But instead of holding the surgical instruments, the surgeon sits at a control panel and moves the instruments with the aid of precise robotic arms. In addition to prostatectomy (surgery to remove the prostate gland), robotic surgery can be used for hysterectomy to treat cervical and endometrial cancers, for gastric bypass and for mitral valve repair, as well as some bladder, throat, thyroid and kidney cancers, and is being investigated in other cancers.

Radiofrequency ablation, or RFA, is an outpatient procedure that utilizes heat delivered through a thin, needle-like probe inserted into the tumor to kill tumor cells. Cryoablation is a similar procedure that uses rapid freezing and thawing to kill the cancer cells.

RADIATION THERAPY

Radiation therapy may be used alone to treat some cancers but is most often used in combination with other therapies to improve the cure rate following surgery. Radiation may also be used to allow less extensive surgery or to relieve side effects of advanced cancer. High doses of radiation may cause side effects after treatment, as well as late effects, such as secondary cancers. Newer specialized techniques target radiation more accurately to tumor sites to minimize these effects.

Types of Targeted Radiation Therapy:

Brachytherapy radiates the tumor directly by implanting radioactive seeds or wires into the body near the tumor. Brachytherapy is used in prostate, cervical and other cancers. Brachytherapy may also be used in breast cancer. Called partial breast irradiation (PBI), it is still considered experimental and is sometimes used for smaller lymph node-negative breast cancers.

Conformal radiation employs several weak beams of radiation originating from different angles that intersect to produce a concentrated high dose of radiation at the tumor site. Advanced conformal therapy, such as intensity-modulated radiation therapy (IMRT), uses multiple beams with varying intensity.

Stereotactic radiosurgery, such as Gamma Knife, uses a computer to simultaneously focus about 200 small beams onto a tumor in the brain while the patient’s head is immobilized in a special helmet. A similar technique, known as CyberKnife, bypasses the need for the helmet by using imaging to make adjustments for movements. Gamma Knife is used for small- to medium-sized tumors in the brain, while CyberKnife is employed for larger tumors and tumors in other areas of the body.

Proton beam therapy uses positively charged particles, called protons, that only travel a certain distance. The method allows doctors to control the depth of radiation more precisely and deliver more of it to tumors while sparing nearby healthy tissue. Proton beam therapy is used for some childhood cancers and certain brain, central nervous system, eye, head and neck, liver, lung and some sarcomas. It’s also being investigated in other cancers, such as breast, esophageal and prostate. Side effects are less intense than with older types of radiation.

CHEMOTHERAPY

While surgery and radiation target the tumor, chemotherapy targets the whole body systemically through a number of mechanisms of action. New chemotherapy drugs are more effective and less toxic than first-generation chemotherapy drugs developed 50 years ago, due to greater knowledge about how to deliver them, including optimal dose and frequency of dose, alone and in combination.

Chemotherapy can be given as the primary—or main—treatment for some cancers, such as lymphoma and leukemia. It can also be given after the cancer has been removed as adjuvant therapy, which may improve survival and delay or prevent disease progression. Neoadjuvant chemotherapy is given before surgery to shrink tumors enough to permit less extensive surgery. When cancer is not curable, palliative chemotherapy can often reduce symptoms caused by tumors.

Classes of Chemotherapy Agents:

Mitotic inhibitors disrupt mitosis, a phase of cell division in which a cell duplicates and separates the chromosomes in its cell nucleus. Mitotic inhibitors include taxanes and vinca alkaloids (which are used to treat some solid tumors, as well as lymphomas and leukemias) and epothilones (which are used to treat advanced breast cancer when taxanes no longer work). Mitotic inhibitors are known for their potential to cause peripheral nerve injury (neuropathy), which can be a dose-limiting side effect.

Alkylating agents are active against blood-related cancers, such as non-Hodgkin lymphoma, Hodgkin lymphoma, chronic leukemias and multiple myeloma, but are also effective in breast, lung, ovarian and some gastrointestinal cancers. Alkylating agents work by damaging the DNA of cancer cells to prevent them from dividing and multiplying.

Antimetabolites interfere with DNA and RNA production. These agents are effective in a specific cycle of cell growth and are used against leukemias, lymphomas and cancers of the ovary, breast, gastrointestinal tract and lung.

Topoisomerase inhibitors interfere with enzymes that are important for accurate DNA replication. They are used to treat certain types of leukemia, as well as colorectal, gastrointestinal, lung, ovarian and other cancers.

Anthracyclines are anti-tumor antibiotics that interfere with enzymes involved in DNA replication. Anthracyclines treat a variety of tumors and work in all phases of the cell cycle. Because they can damage the heart muscle, anthracyclines have a lifetime dose limitation.

STEM CELL TRANSPLANTATION

Bone marrow, the spongy material inside the bone, is the natural home for hematopoietic stem cells (HSCs), the “parent cells” that develop into different types of blood cells. These stem cells can be retrieved from either the patient (called an autologous transplantation) or a donor (called an allogeneic transplantation). Patients who provide their own HSCs have them removed from the bone marrow or the bloodstream prior to chemotherapy or radiation, and the cells are frozen for later use. In other cases, the HSCs come from a donor, which may be an identical twin, another close relative (often a sibling), an unrelated person or even ffrom an unrelated newborn. Patients with leukemia, myeloma, low-grade lymphoma, myelodysplastic syndromes and, less often, various other cancers, may be treated with a stem cell transplantation.

HORMONE THERAPY

Hormone therapies interfere with the interaction of sex hormones (androgens and estrogens) and some types of cancer, particularly breast and prostate. Hormone therapy can be used alone or with other treatments (as adjuvant therapy).

Following surgery, women with breast cancer that is shown to be fueled by estrogen are treated with an estrogen blocker and/or newer drugs, called aromatase inhibitors. These drugs are taken for at least five years, although some studies suggest the optimal length of time may be 10 years.

Aromatase inhibitors block an enzyme that converts androgens to estrogens in postmenopausal women. Patients with prostate cancer may receive androgen deprivation therapy to lower testosterone levels. Another group of drugs, known as anti-androgens, are sometimes helpful if other hormone therapies stop working. Removing the ovaries or testicles can also reduce the level of sex hormones.

TARGETED THERAPY

Researchers have learned more about specific molecular changes responsible for cancer growth, resulting in new drugs called targeted, or biologic, therapy. These drugs target genes or proteins in the cell. However, many of these newer agents must be combined with traditional chemotherapy, and some carry their own side effects, such as rash, diarrhea, heart malfunction or high blood pressure.

Types of Biologic Therapy:

Monoclonal antibodies were among the first targeted agents. In 1975, researchers mass-produced antibodies of a single (mono) type in the laboratory. Initially, these “monoclonal” antibodies, often referred to as MoAbs or MAbs, were made entirely from mouse cells, so the human immune system recognized them as foreign, and in some cases, destroyed the MoAbs before they could be helpful. Today, researchers have replaced some parts of these mouse antibody proteins with human parts, making some MoAbs from fully human sources. An even newer approach uses fragments of antibodies instead of whole ones to better reach a tumor.

The Food and Drug Administration has approved MoAbs for non-Hodgkin lymphoma, some leukemias, advanced melanoma, and HER2-positive breast, gastric, advanced colorectal, and head and neck cancers. The FDA has also approved two radioactive antibody-based drugs that bring radioactive atoms directly to the cancer cells.

MoAbs are now also being combined with chemotherapy, forming an antibody-drug conjugate to deliver the chemotherapy agent to a specific biologic target. The FDA has approved this type of treatment for HER2-positive breast cancer and certain types of lymphoma.

Angiogenesis inhibitors prevent angiogenesis, the formation of new blood vessels in the tumor. Shutting down a tumor’s blood supply shrinks the tumor, which needs nutrients and oxygen from blood to survive and grow. Most anti-angiogenic drugs target either a protein secreted by certain tumors to promote the growth of new blood vessels (called vascular endothelial cell growth factor, or VEGF) or the VEGF receptor on blood vessel cells.

Anti-angiogenic drugs that are not monoclonal antibodies have been approved for colorectal, kidney, liver and thyroid cancers, as well as gastrointestinal stromal tumors (GIST) and multiple myeloma.

Kinase inhibitors block enzymes with a variety of functions, including angiogenesis, growth factor receptors and other aspects of cell signaling, and are used in treating certain breast, colorectal, kidney, non-small cell lung, pancreatic and thyroid cancers, as well as GIST, some leukemias and soft tissue sarcoma.

Proteasome inhibitors treat multiple myeloma and mantle cell lymphoma by blocking multi-enzyme complexes called proteasomes that break down proteins involved in regulating cell processes relevant to cancer.

mTOR inhibitors block the mammalian target of rapamycin (mTOR), a key protein in cells that regulates cell growth and survival. These inhibitors block the translation of genes that regulate the cell cycle and reduce levels of certain cell growth factors involved in the development of new blood vessels, such as VEGF. Several mTOR inhibitors are currently used for breast, advanced kidney and other cancers.

Other inhibitors that have been approved include one for basal cell carcinoma that blocks the hedgehog pathway, a celluar pathway involved in controlling cell division, and another for chronic myeloid leukemia that targets protein synthesis in the cell, thus halting cancer growth.

Immunotherapy uses the body’s immune system to stimulate the production of T-cells (immune cells that recognize and kill cancer cells). Naturally occurring substances in the body (cytokines) have been found to increase T-cell activity and signal the body to produce more T-cells. Some cytokines, such as interleukins and interferons, can be produced in the laboratory and are used to treat melanoma, kidney and bladder cancers. Other targeted immunotherapies also treat multiple myeloma. Therapeutic vaccines program the body’s immune system (both antibodies and T-cells) to recognize and attack cancer cells, sparing the normal tissue. One such vaccine is currently used for prostate cancer.