Medical brain notes 42

  Cell Biology and Principles of Cancer Therapy Treatment of cancers involving the breast and gen ital organs may involve surgery, chemotherapy,radiation therapy, or hormone therapy, used alone or in combination. The specific treatment plan depends on  the type of cancer, the stage of the cancer, and the charac-teristics of the individual patient.  Individualizing treatmentis an important aspect of cancer therapy.   CELL CYCLE AND CANCER THERAPY   Knowledge of the cell cycle is important in understand-ing cancer therapies. The ideal cancer treatment would be a drug that targets only cancer cells with no effect on healthy tissues. In order to optimally target only cancerous tissue, it is imper-ative to understand not only how normal cells function, but also how cancer cells differ from normal cells. Many treatments are based on the fact that cancer cells are constantly dividing, making them more vulnerable to agents that interfere with cell division.   The c...

  CHEMOTHERAPY   Chemotherapeutic agents  can be (1)  cell cycle (phase)-nonspecific,  which means that they can kill in all phases ofthe cell cycle and are useful in tumors with a low growth index, or (2)  cell cycle (phase)-specific,  which means that they kill in a specific phase of the cell cycle and are most use-ful in tumors that have a large proportion of actively divid-ing cells. Figure 40.1 illustrates common drugs and their sites of action within the cell cycle.   Several classes of  antineoplastic drugs  are available (Table 40.1).  Alkylating agents  and  alkylating-like agents  bind and cross-link DNA, interfering with DNA replica-tion and, ultimately, with RNA transcription. Dividing cells, especially those in the late G 1  and S phases, are most sensitive to the effects of these drugs; however, these drugs are considered phase-nonspecific (i.e., they are effective in all phases of the cell cycle). ...

  RADIATION THERAPY   Ionizing radiation  causes the production of free hydrogenions and hydroxyl ( OH) radicals. With sufficient oxygen, hydrogen peroxide (H 2 O 2 ) is formed, which disrupts the structure of DNA and, eventually, the cell’s ability to divide. As with chemotherapy, killing is by first-order kinetics.  Because dividing cells are more sensitive to radiation damage and because not all cells in a given tumor are dividing at any one time, fractionated doses of radiation are more likely to be effective than a single dose.  Providing multiple lower doses of radiation alsoreduces the deleterious effects on normal tissues.   The basis of fractionated dosage comes from the  “four Rs” of radiobiology:   ·       Repair of sublethal injury.  When a dose is divided,the number of normal cells that survive is greater than if the dose were given at one time (higher total amounts of radiation can be tolerated in fracti...

  NOVEL CHEMOTHERAPEUTIC AGENTS   The next horizon for cancer treatment is molecularly tar-geted agents, cancer vaccines, and gene therapy. Several drugs are currently available that target specific mole-cules or proteins in cancer cells. For example, trastuzumab is a DNA-derived monoclonal antibody to the human epidermal growth factor receptor 2 protein (HER-2). Treatment with trastuzumab is currently indicated in patients with metastatic breast cancer whose tumors over-express HER-2. Some ovarian, cervical, and endometrial tumors express the HER-2/ neu  receptor; therefore, investi-gation is currently ongoing regarding the usefulness of this agent in gynecologic tumors. Additionally, bevacizumab is a monoclonal antibody designed to target the VEGF pro-tein and inhibit angiogenesis in tumors. It is currently under investigation for possible treatment of a variety of tumors, including epithelial ovarian cancer.   Tumor vaccines  are also currently being investig...