Chemotherapy
Most, if not all, chemotherapeutic agents kill cancer cells through the induction fo apoptosis.
Specific Chemotherapeutic agents
Colchicine: has been investigated as an anti-cancer agent and has proven to be effective in treating cancerous cells. However, colchicine brutally damages a cell’s inner layers by blocking the action of a protein called tubulin. Tubulin plays an important role as cells divide into two. Thus, colchicine effectively halts cell division. Stopping cell division is a vital part of potential cancer drugs. Unfortunately, colchicineattacks not only cancer cells, but healthy ones as well, classifying it as a poison. One strategy to deal with this has been proposed by Laurence Patterson, Professor of Drug Discovery and Institute Director of the Institute of Cancer Therapeutics at the University of Bradford. Patterson uses a drug delivery system that targets colchicine directly to the target. Many cancers produce a lot of enzymes called matrix metalloproteases (MMPs) which are useful to the cancer because they can disolved extracellular matrix around cells and give the cancer cells access to new blood vessels. Patterson attach long molecular tails to colchicine molecules which target the colchicine directly to the cancer cells. The colchicine is nontoxic until it comes into contact with MMP1, a metalloprotease protein released by tumors.
Side Effects oc Chemotherapeutic agents
Chemotherapy suffers from problems like drug toxicity and drug resistance (due to increased drug metabolism, increased DNA repair mechanisms and decreased drug import into cells). Although chemotherapeutics and radiation exposure can effectively kill rapidly proliferating tumor cells, the rapidly dividing stem cells of the host’s mucosal epithelium, including the stem cells of the interstinal crypts and epidermis, are also damaged or killed, leading to the clinical condition termed “mucositis”. Oral and gastrointestinal mucositis can be sufficiently painful or debilitating to deter patients from continuing their course of treatment. Cytotoxic chemotherpay is known to cause mucosal injury (MI) both in the oral cavity and to mitotically active intestinal crypt cells. The manifestations of oral mucositis include erythema, ulcer formation, bleeding and exudates. Most of patietns treated for head and neck cancer and almost half of the patients receiving chemotherpay for non-head and neck cancer develop oral complications. The effect of radiation therpay on oral cavity primarily results form local tissue changes. These changes are initiated by a reduction in the prolfieration of basal epithelial cells, causing atrophy. Compromise of the mucosal barrier can also contribue to local invasaion by colonizing microorganisms and, subsequently, to systemic infection (Khan, “Infection and Mucosal Injury in Cancer Treatment, 2001).
Recombinant human keratinocyte growth factor (rhKGF, sold as Kepivance by Amgen, Inc, used as pretreatment, has been shown to cause an increase in measures of mucosal thickness and a 3.5 fold improvement in crypt surfival in the small intestine.
Drugs which Counteract Side-Effects
Granulocyte colony stimulating factor: is used to stimulate neutrophil production in patients udnergoing chemotherapy. Amgen, for example, sells Neupogen® (filgrastim) which is a recombinantly products version of G-CSF and FDA approved for cancer patients receiving myelosuppressive chemotherapy, actue myeloid leukemia patients receiving induction or consolidation chemotherapy, patients udneroing bone marrow transplantation, autologous periopheral blood progenitor cell collection and therapy and patients with severe chronic neutropenia. Sandoz has recentrly received approval for a biosimilar under the provisions of the Biologics Prcie Competition and Innovation Act (BPCIA).