Radiotherapy tumor cells, effects

The three main treatment modalities currently available to cancer patients are surgery, radiotherapy, and chemotherapy [1], Radiotherapy and chemotherapy non-selectively inhibit rapidly proliferating cells, including cancer cells, and the generality of the antiproliferative effect of these treatments leads to the severe dose-limiting toxicides experienced by cancer patients. In addition, the genetic instability of tumor cells facilitates the development of resistance to radiotherapy and cytotoxic chemotherapy that eventually causes these treatment approaches to fail in most patients with solid or metastatic tumors. 

One of the varieties of malignant tumor radiotherapy is neutron capture therapy (NCT) (De Stasio et al., 2001). NCT is a cancer therapy that uses radiation from the reaction of capturing thermal neutrons by or Gd isotopes, previously accumulated in tumor cells (Detta and Craickshank, 2009 Turanska et al., 2010). The result of thermal neutron interaction with isotopes is a significant cytotoxic effect caused by the influence of the products of nuclear reaction on cancer cells. 

Fig. 10.6. Mechanisms of chemoradiation on a cellular level. At least four major mechanisms contribute to the efficacy of the combination of radiation with chemotherapy. In general, the addition of chemotherapy adds to the combined effect simply by an additional independent killing of clonogenic tumor cells. This mechanism is backed up by several other more interactive pathways chemotherapy may induce a certain reassortment of tumor cells in more vulnerable phases of the cell cycle, chemotherapy may reduce the level of repopulation during a course of fractionated radiotherapy, and, finally, chemotherapy may partially overcome hypoxia-mediated radiation resistance...

The combination of radiotherapy and chemotherapy is a promising approach because of its independent cell kill effect and the property of some cytotoxic agents to enhance the effect of radiotherapy. At the end of the 1970s, platinum complexes were described as being able to act as potent radiosensitizers of hypoxic tumor cells (Dou-PLE and Richmond 1978,1979). As an obstacle in this type of chemoradiation, Koukourakis etaL (2002) have suggested that (hypoxia-induced ) overexpression of HIF-1 a in patients with head and neck cancer may be related to substantial resistance to carboplatin chemo-radiotherapy. More in-depth research is needed to accurately characterize adverse effects of hypoxia in this type of combination therapy. 

Effective tumor control can be achieved by the use of substances that can increase the sensitivity of the tumor cells for chemotherapeutic agents and therefore reduce the side effects for the normal cells. Withaferin A (2), the major constituent of the Withania somnifera, was found to be a potent radiosensitizing agent when administered before radiotherapy. The effect was studied on B16F1 melanoma and fibrosarcoma mouse tumors grown in C57BL and Swiss albino mice, respectively. The study concluded that the radiotherapy response of both tumors increased substantially on administration of withaferin A (2) [87]. 

The efficacy of radiotherapy is not clear. Several studies have shown a tumor control rate as different as 90% and 25%. The mechanism of treatment is due to its effect on the vascular component causing vascular arteritis and fibrosis rather than affecting the tumoral cells. Brain tissue necrosis is an undesirable side effect related with this method and is usually detectable by CT or MRI. 

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