Cancer is a leading cause of death worldwide, accounting for about 7 million deaths every year, with an estimated 24 million people living with cancer. In the United States, an estimated 1.4 million new cases are expected for 2009, with well over 500,000 deaths.
Though there is no definite cure for many cancer types, there have been steady advances in treatment with much improved outlook in many cases in terms of remission rates, prolongation and quality of life. Treatment modalities include chemotherapy (with drugs), radiotherapy and surgery, with adjunct and palliative therapy to improve quality of life. Anticancer drugs continue to play a very strong role in the treatment of cancer.
Cancer Biology
Normal cells mature and divide under strict controls. They go through a resting phase (interphase), during which growth and development with protein synthesis and ribonucleic acid (RNA) and deoxyribonucleic acid (DNA) synthesis take place. Some cells, like nerve cells, stay permanently at this stage. Others, especially epithelial cells, continue to "M" phase, where they divide in a process called mitosis.
Cancer usually develops from a complex interplay of environmental and toxicological influences and genetics to produce a malignant change in a cell population. Any part of the body is involved. A cell that begins to divide out of control with invasion of neighboring organs has undergone malignant change. Transplanting to other tissue sites is called metastasis, a major cause of death in cancer cases.
Anticancer Mechanisms
The main characteristic of malignant cells is rapid, uncontrolled cell division. Anticancer drugs are thus designed around directly affecting the process of cell division or indirectly by affecting factors or environments that encourage the continued multiplication of these malignant cells.
Alkylating agents like chlorambucil (breast cancer), cisplatin (bladder cancer) and cyclophosphamide (non-Hodgkin's lymphoma) alter the DNA crosslinkages, interfering with DNA transcription and protein synthesis.
Antimetabolites like thiouracil (bladder cancer), methotrexate (breast cancer) and mercaptopurine (leukemia) act by substituting essential metabolites with ineffective alternatives in essential steps in either protein synthesis or nucleic acid replication.
Antibiotics like bleomycin (testicular cancer), doxorubicin (leukemia) and dactinomycin (Kaposi's sarcoma) act by damaging single and double-stranded DNA, disrupting protein synthesis and stopping cell division.
Mitotic inhibitors like paclitaxel (ovarian cancer) and vincristine (lung cancer) intercalate with the mitotic spindles and "freeze" the mitotic phase.
Biological response modifiers or immune modulators like interleukin-2 (renal cell carcinoma), interferon alpha (leukemias) and monoclonal antibodies (trastuzumab in breast cancer) are natural defense products of white blood cells targeted at specific sites on the tumor cells that increase their clearance from the body.
Hormonal anticancer drugs hormones or hormone antagonists act to alter otherwise favorable hormonal environments for cancer growth, like tamoxifen in breast cancer and estrogen in prostate cancer.
Radio-pharmaceuticals, like Iodine-131 in Thyroid cancer, are natural compounds labeled with radioactivity and targeted at specific cancers that usually concentrate the compounds. They deliver comparative radioactivity with radiotherapy.
Other miscellaneous agents like tretinoin, asparaginase and levamisole are not clearly understood as to their exact mechanism of action.
Certain combinations of drugs are used at times to maximize effects, reduce dose related toxicity and overcome resistance to the drugs.
Adverse Effects
Normal cells, particularly those that are rapidly dividing like bone marrow, intestinal mucosa, hair follicles and gonads are also affected by anticancer drugs. Thus, hair loss, nausea, vomiting and diarrhea, bone marrow suppression and fetal loss or malformations are common side effects to almost all anticancer drugs.
Some agents have specific toxicity for certain organs like doxorubicin for the heart, bleomycin for the lungs, cyclophosphamide for the liver and cisplatin for the kidneys.
