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 you 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. The main benefits are faster recovery times, shorter hospital stays and fewer complications.

Robotic surgery may have even more benefits for you. 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. 

Radiofrequency ablation, or RFA, is an outpatient procedure where a thin needle-like probe is inserted into the tumor. The tip is then heated 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 techniques target radiation more accurately to tumor sites to minimize these effects.

View Illustration: Radiation Manipulation

TYPES OF TARGETED RADIATION THERAPY:

Brachytherapy radiates the tumor directly by implanting radioactive seeds or wires directly into the body near the tumor. Brachytherapy is used in prostate, cervical and some other cancers. Brachytherapy may be used in breast cancer by implanting radiation into the lumpectomy cavity using a balloon catheter. This partial breast irradiation (PBI), still considered experimental, is increasingly being used for smaller lymph node-negative breast cancers and can be completed in a few days instead of the usual six weeks.

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. Gamma Knife is used for small- to medium-size tumors in the brain, while CyberKnife is employed for larger tumors. 

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 some prostate, brain, lung, esophageal, and head and neck cancers. Side effects are less intense than with conventional radiation. Experts say clinical research still needs to determine whether proton beam therapy works better than standard radiation therapy at improving survival and quality of life. Several proton beam radiation centers are now open in the U.S., with more scheduled to open soon.

Chemotherapy

While surgery and radiation target the tumor, chemotherapy targets the whole body through a number of mechanisms of action. New chemotherapy drugs have greater efficacy and less toxicity 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, such as Taxol (paclitaxel), Taxotere (docetaxel) and a newly approved advanced prostate cancer drug, Jevtana (cabazitaxel). Also included are the vinca alkaloids, including Velban (vinblastine), Oncovin (vincristine) and Navelbine (vinorelbine), which are used to treat some solid tumors, as well as lymphomas and leukemias. Epothilones, such as Ixempra (ixabepilone), 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. The newest inhibitor, Halaven (eribulin), is derived from a sea sponge and was approved in late 2010 for metastatic breast cancer. 

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, ovarian, lung and some gastrointestinal cancers. Some examples include cisplatin, carboplatin, Eloxatin (oxaliplatin), Cytoxan (cyclophosphamide), Ifex (ifosfamide) and Treanda (bendamustine). Alkylating agents work by damaging the DNA of cancer cells to prevent them from dividing and multiplying.

Antimetabolites are in a class of drugs that interfere with DNA and RNA production. Examples include Gemzar (gemcitabine), 5-FU (fluorouracil), Xeloda (capecitabine), Cytosar-U (cytarabine), Alimta (pemetrexed) and Folotyn (pralatrexate). These agents are effective in a specific cycle of cell growth and are used in leukemia, lymphoma and cancers of the ovary, breast, gastrointestinal tract and lung.

Topoisomerase inhibitors, such as Camptosar (irinotecan) and Hycamtin (topotecan), interfere with enzymes that are important for accurate DNA replication. They are used to treat certain types of leukemia, as well as colorectal, lung, ovarian, gastrointestinal 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. Adriamycin (doxorubicin), Ellence (epirubicin) and Cerubidine (daunorubicin) are the more commonly used anthracyclines.

Stem Cell Transplant

Bone marrow, the spongy material inside the bone, is the natural home for hematopoietic stem cells, the “parent cells” that develop into different types of blood cells. These stem cells can be “harvested” or removed from the blood using machines that separate blood components. Patients with leukemia, myeloma, low-grade lymphoma, myelodysplastic syndromes and, less often, various other cancers, may be treated with a stem cell transplant.

High doses of radiation and/or chemotherapy have the unwanted side effect of damaging a patient’s bone marrow stem cells. Thus, stem cell transplants “rescue” patients from this high-dose treatment. Returning stem cells from the patient’s own body after high-dose treatment is known as an autologous transplant. Transplantation of stem cells from a related or unrelated donor whose tissue type matches that of the patient is called allogeneic transplant.

View Illustration: Types of Stem Cell Transplant

Over time, the infused  cells find their way to the bone marrow, where they divide and mature into cells normally produced by healthy bone marrow. This process is known as engraftment.

Graft-versus-host disease, or GVHD, may occur after allogeneic transplants if the donor immune cells view the recipient’s body as foreign. The recipient’s immune system has largely been destroyed by conditioning treatment and cannot fight back. The donor immune cells may attack certain organs (most often the skin and liver), which impairs the organs’ ability to function and increases the chance of infection. 

About one-third to half of allogeneic transplant recipients develop acute GVHD within 25 days on average, which can be serious and sometimes fatal. However, a small amount of GVHD can actually be helpful since the transplanted immune cells can also attack residual cancer cells.

Hormonal Therapy

Hormonal therapies interfere with the interaction of sex hormones (androgens and estrogens) and some types of cancer, particularly prostate and breast. Hormonal 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 tamoxifen and/or newer drugs called aromatase inhibitors, which include Femara (letrozole), Arimidex (anastrozole) and Aromasin (exemestane).These drugs are taken for at least five years, although the optimal length of time is not yet known. 

Aromatase inhibitors block an enzyme that produces small amounts of estrogen in postmenopausal women. Prostate cancer patients may receive androgen deprivation therapy to lower testosterone levels. Another group of drugs, known as anti-androgens, are sometimes helpful if other hormonal 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 biological, 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, heart damage or high blood pressure.

Types of Biological 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, abbreviated 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 MAbs before they could be helpful. Today, researchers have replaced some parts of these mouse antibody proteins with human parts. Some MAbs are now fully human. An even newer approach uses fragments of antibodies instead of whole ones to better reach a tumor. 

In the past 10 years or so, the Food and Drug Administration has approved several MAbs, including Rituxan (rituximab) for non-Hodgkin lymphoma and some leukemias, Herceptin (trastuzumab) for HER2-positive breast and gastric cancers, Erbitux (cetuximab) for advanced colorectal and head and neck cancers, Vectibix (panitumumab) for advanced colorectal cancer, Yervoy (ipilimumab) for advanced melanoma and Arzerra (ofatumumab) for chronic lymphocytic leukemia. Zevalin (ibritumomab tiuxetan) and Bexxar (tositumomab), both for non-Hodgkin lymphoma, are currently the only radioactive antibody-based drugs approved by the FDA. These drugs use MAbs that bring radioactive atoms directly to the cancer cells.

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 antiangiogenic drugs target either a protein secreted by certain tumors to promote the growth of new blood vessels called vascular endothelial cell growth factor (VEGF) or  the VEGF receptor on blood vessel cells. Avastin (bevacizumab) was the first successful drug to inhibit angiogenesis.

Avastin is approved in combination with chemotherapy for advanced colorectal, non-small cell lung and kidney cancers, as well as glioblastoma. The drug has shown benefit with chemotherapy in clinical studies for a variety of other cancers, including gastric. 

Antiangiogenic drugs that are not monoclonal antibodies include Revlimid (lenalidomide) and thalidomide, both for multiple myeloma; Sutent (sunitinib) for kidney cancer and gastrointestinal stromal tumors (GIST); Nexavar (sorafenib) for kidney and liver cancers; and Votrient (pazopanib) for kidney cancer.

View Illustration: Cancer Therapy's Many Targets

Tyrosine kinase inhibitors block enzymes with a variety of functions, including angiogenesis, growth factor receptors and other aspects of cell signaling.

The drug Gleevec (imatinib) has changed the way doctors treat people with chronic myeloid leukemia (CML) and GIST. Almost all cases of CML have the Philadelphia chromosome, created when parts of chromosomes 9 and 22 break off and switch places. This produces an abnormal protein called bcr-abl, which is in a class of enzymes called tyrosine kinases. 

Gleevec inhibits bcr-abl. Almost all patients respond to this oral drug. Side effects are fewer than with traditional chemotherapy or interferon. Two new drugs, Sprycel (dasatinib) and Tasigna (nilotinib), are now also approved for patients with CML. Tarceva (erlotinib), a kinase inhibitor approved for non-small cell lung cancer and pancreatic cancer, blocks the overexpression of the epidermal growth factor receptor, or EGFR. Tykerb (lapatinib) inhibits both EGFR and HER2 and is approved in combination with Femara for advanced HER2-positive breast cancer and estrogen-positive advanced breast cancer. 

Proteasome inhibitors, such as Velcade (bortezomib), 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. Two mTOR inhibitors are used for advanced kidney cancer: Torisel (temsirolimus) and Afinitor (everolimus). 

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 called 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. Therapeutic vaccines program the body’s immune system (both antibodies and T-cells) to recognize and attack cancer cells, sparing the normal tissue. Only one therapeutic vaccine has been approved, Provenge (sipuleucel-T) for adavnced prostate cancer, but many clinical trials, including those for breast and brain cancers, are ongoing. 

The principles of cancer therapy are straight-forward—eliminate as much of the cancer as possible using surgery, radiation or chemotherapy, individually or in combination, while leaving normal cells unharmed. But as simple as these principles are, the required expertise comes from different disciplines, including pathology, surgery, radiation and medical oncology.

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