Cancer has always been a topic of interest for me. When I was around eight my grandmother died from breast cancer at age 52 and since then I’ve had a wonder about the disease. The more I looked into the science and medical area the more I saw I was proficient in it and thought “I could become a doctor and further cancer research myself” so that is the plan of action for the next seven years. In the meantime, learning more about the disease and keeping up with terminology and new discoveries will aid my progression into that community and hopefully ease my workload a little in medical school. Class assignments similar to this also help motivate my research because all of us get bored of things after a while and these keep re-igniting the flame for me, thankfully.
Tumors are collections of cancer cells that do not serve any bodily function and can obstruct vital organs or cause complete organ failure. What defines a cancer cell is a cell that replicates too quickly and never enters G0 phase (the dormant stage of a cell in which it does not replicate itself and only expends energy on normal cellular function). Basically, the cells replicate to a point where the cells build up to a mass and the cells cannot function or they function incorrectly because they replicated too quickly to develop proper internal structure for that cell type. Tumors are first benign, meaning it does not spread and stays local, but as soon as it enters another area of the body it is considered malignant and poses a much higher threat to the individual. Once the cancer has progressed this far, it become much harder to treat and if the cancer is resisting treatment to begin with, it is pretty much assumed terminal and you’ll get an estimated time to live based on how far the cancer has progressed and what stage you are in (stage 1-4). A stage 1 cancer is normally treatable or operational but anything stages 2-4 is considered terminal with varying degrees and usually people don’t respond well to the news.
Some cancers are naturally resistant to chemotherapy and cancer fighting drugs but others diminish and later return with a resistance to the drug. This makes is why when a cancer comes back after it’s been treated once already, doctors usually use a secondary method of treatment because they know the cancer has become resistant to the first method. Peter Shelby writes in the British Medical Journal, “most times, biological resistance of cancer cells to drugs is because of biochemical changes within tumor cells”. Larry E. Hogwood concurs with that statement and describes more in depth that reasons for ineffective drugs treatments are altered target enzymes, gene amplification and surface glycoproteins being present which inhibits the drug from entering the cell.
Manson, Scott R., Benjamin E. Derverman, and Steven J. Weintraub. “Resistance to Antineoplastic Therapy.” Cell Press. Elsevier Inc, 2004. Web. 7 April. 2016.
Zhao and coworkers present the findings of studies in which they used a transgenic mouse model of T cell lymphoma to dissect the components of the transforming function of an activated form of the Src-related tyrosine kinase Lck. They compared the effects of two different levels of Lck activity on the response to γ radiation and etoposide. Amazingly, even though the p53 signaling pathway was equally responsive to treatment in thymocytes expressing either “intermediate activity” (higher activity than wild-type Lck, but nononcogenic) or “hyperactive” (oncogenic) Lck, and both levels of Lck activity induced expression of similar levels of Bcl-xL, the “hyperactive” Lck was strikingly more effective in preventing both γ radiation-induced and etoposide-induced apoptosis (the death of cells that occurs as a normal and controlled part of an organism’s growth or development).
Selby, Peter. “Acquired Resistance to Cancer Chemotherapy”. British Medical Journal (Clinical Research Edition) 288.6426 (1984): 1252–1253. Web. 7 April. 2016.
Many cancers are naturally resistant to cancer treatment such as malignant melanoma or colorectal carcinoma. Some others are diminished by treatment but later on return because the cancer becomes drug resistant. Most times, biological resistance of cancer cells to drugs is because of biochemical changes within tumor cells. When human and murine tumors are exposed to continuous or graded concentrations of methotrexate in vitro they become resistant for several reasons. One of which is because uptake of the drug by the cells is reduced. Mutant enzymes with a low affinity for the drug may be synthesized or the amount of dihydrofolate reductase may be increased. Resistant cells have greater excess of dihydrofolate reductase genes.
Hopwood, Larry E., and John E. Moulder. “Radiation Induction of Drug Resistance in RIF-1 Tumors and Tumor Cells”. Radiation Research 120.2 (1989): 251–266. Web. 6 April 2016.
For the most part, drug-resistant cells in tumors account for the failure of chemotherapy, used alone or combined with radiation. Reasons for the cell being resistant to treatments are altered target enzymes, defective transport, the drug not activating, gene amplification, surface glycoproteins being present, and abundance of drug inactivating enzyme. Goldie, Coldman and Skipper created mathematical models that help determine drug resistance after the primary wave of treatment and observing the mutants that resisted it and will subsequently not be affected by later similar treatments. They work by assuming background frequency of drug resistant cells. Tumors do not show any mutations initially after radiation therapy. Instead, it is assumed that the wild type gene is diluted before any of the mutated genes are expressed and this takes place over several replications. The delay between irradiation and the expression of drug resistance by radiation-induced mutants may be an important consideration in the scheduling of combined radiation and chemotherapy treatments.