Chemotherapeutic sensitivity

The first platinum drugs entered human clinical trials in 1971—1972. The trials culMnated in 1978 in the United States with approval for use of cisplatin in the treatment of testicular and ovarian cancers, and later to bladder cancer. Using the definition of chemotherapeutic sensitivity as in Table 2JII [8], a summary of the present clinical utility is given in Table 2.IV. 

The pro- and antiapoptotic members of the Bcl2 family affect cellular sensitivity to apoptosis and thus to many chemotherapeutic agents [4]. For example, overexpression of the antiapoptotic genes Bcl2 and Bcl-XL in some cell lines and tumors can confer resistance to apoptosis triggered by ionizing radiation. Conversely, overexpression of proapoptotic Bax in experimental tumors can induce apoptosis directly or render such tumors more sensitive to cisplatin and 5-FU. 

Swanton, C., Marani, M., Pardo, O. et al. 2007. Regulators of mitotic arrest and ceramide metabolism are determinants of sensitivity to paclitaxel and other chemotherapeutic drugs. Cancer Cell, 11 (6) 498—512. 

In addition to trying to improve the results of standard chemoradiation by intensifying chemotherapy and/or radiation, a second approach has been to combine radiation therapy with some of the newer chemotherapeutic agents, which are also known to be potent radiation sensitizers. These agents have been used both in primary chemoradiation protocols, as well as in the preoperative setting. 

Zhang L, Hung MC. Sensitization of HER-2/neu-over-expressing non-small cell lung cancer cell to chemotherapeutic drugs by tyrosine kinase inhibitor emodin. Oncogene 1996 12 571-576. 

---