Other non phase-specific drugs

There are several drugs that act in all phases of the cell cycle.

Anthracyclines – These drugs originally isolated from a soil-dwelling fungus, form free oxygen radicals that prevent DNA synthesis by breaking the DNA strands. They are effective across many types of cancer. Their major drawback is the particularly toxic effect they can have on heart muscle. Anthracyclines came into use, beginning in the 1970s.

Idamycin (idarubicin) was approved for the treatment of leukemia in 1990,
DanuoXome (danurubicin) was approved in 1996 for treatment of Karposi’s sarcoma.
Ellence (epirubicin) was approved for treatment of a variety of cancers in 2006 ,

Platinums - Platinums are natural metal derivatives that create cross-links in DNA peptide bonds during any phase of the cell cycle. The first platinum-based chemotherapy drug, cisplatin, was approved in 1978. Like other drugs that create cross-bonds, platinum-based chemotherapy drugs can have a toxic effect on other organs, specifically the kidneys.

Antitumor antibiotics – Japanese researchers discovered antitumor properties of the antibiotic Bleomycin in the 1960s. Bleomycin creates free oxygen radicals that break DNA strands, similar to anthracyclines. In 1973 Bleomycin was approved by the FDA as Blenoxane. Brand and generic forms of Bleomycin are in use today with caution due to possible toxic effects on the lungs. A second drug, hydroxyurea, classified as an antiviral drug that breaks DNA strands and is most effective for blood-based cancers, was FDA-approved in 1967.

Combination Therapies

In the mid 1960s, researchers began to experiment with combinations of drugs, such as pairing drugs that work in different phases of the cell cycle, to fight cancer. This method remains in prominent use today, with many regimens identified by anagrammatic names such as ABVD or adriamycin, bleomycin, vinblastine and dacarbazine or R-CHOP, R-CHOP is rituximab (monoclonal antibody), cyclophosphamide doxorubicin (originally called Adriamycin), vincristine (Oncovin) and prednisolone, a steroid.

Longitudinal Therapies

Chemotherapy is often administered in conjunction with other therapies. Adjuvant chemotherapy is given after surgical removal of cancerous tissue as a way to eliminate any trace of cancer left or any metastasis that may have occurred. Neoadjuvant therapy uses chemotherapy to shrink tumors prior to surgery. Combination therapy uses chemotherapy in conjunction with radiation or surgery.

Targetted Therapies

As cancer research provides insight into the ways that cancer cells function, cancer treatment is moving from traditional chemotherapy drugs to drugs that can differentiate between healthy cells and cancer cells and target their interventions directly at the cancer. These non-chemotherapy drugs are making major improvements in the treatment of cancer because their cancer cell-specific action dramatically reduces the side effects associated with traditional chemotherapy. More on targeted therapies.

Kinase inhibitors

In the normal cell, cell growth is stimulated by the presence of a growth factor. In the cancerous cell, cell growth takes place without the need for growth factor. This ability is connected to a mutation in the gene for kinase, an enzyme involved in cell reproduction. Kinase inhibitors “turn off” the kinase pathway that allows for uncontrolled cell growth.

Gleevac (imatinib) was one of the first kinase inhibitors to be approved, moving rapidly through the FDA review process with approval in 2000 for leukemia.
Tarceva (erlotinib) was approved for lung cancer in 2004.
Iressa (gefitinib) was approved in 2005 for the treatment of lung cancer.
Nexavar (sorafenib tosylate )was approved in 2005 for the treatment of kidney cancer
Sutent (sunitinib) was approved for gastrointestinal cancer and advanced kidney cancer in 2006.

Monoclonal antibodies

Monoclonal antibodies are proteins synthesized in the laboratory that target specific cancer cells. These antibodies can be fused with toxins and carry those toxins directly to specific can cells. For example:

Herceptin (trastuzumab) was approved for metastatic breast cancer in 1998
Erbitux (cetuximab) was approved in 2004 for colorectal cancer.
Velcade (bortezomib) was approved for the treatment of multiple myeloma in 2003.
Avastin (bevacizumab), a therapeutic antibody, goes beyond simply bringing other drugs to cancer cells. Avastin actually inhibits the development of blood vessels that feed tumors. Avastin has been approved for use in combination with several other drugs for treatment of colorectal cancer, beginning in 2004.

Protective approaches

Research has also provided opportunities to package chemotherapeutic drugs differently to reduce side effects. Liposomal therapy encapsules drugs in a synthetic fat globule which increases penetration of cancer cells and reduces side effects. For example, Doxil, the encapsulated form of doxorubicin, was approved by the FDA in 1999.

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