Overcoming drug resistance of ovarian carcinoma cell lines by treatment with combination of TNF-α/anti-Fas antibody and chemotherapeutic drugs or toxins
Current conventional therapies in the treatment of neoplastic diseases consist of surgery, chemotherapy, radiotherapy and combination therapy. While these forms of treatment have resulted in cures and prolonged survival, recurrent tumors and metastases continue to be very common. Treatment of these recurrent tumors has posed a major challenge to oncologists since these tumors become refractory to chemotherapeutic drugs and metastases are not amenable to surgery or radiotherapy. Thus, the development of tumor cell resistance to cytotoxic drugs has provoked the search for new means to overcome resistance. During the last few years, a surge of new approaches in cancer therapy has emerged that include biological response modifiers to boost the immune response, the use of activated cytotoxic cells such as LAK and TIL and the preparation of ’magic bullets’ consisting of targeted antibody-drug/toxin conjugates, the use of recombinant cytokines (e.g. TNF-α, IFN-γ, IL-2 etc.) and more recently, genetic engineering techniques to modify tumor cells or lymphocytes. Furthermore, new agents to reverse the multidrug resistance phenotype have been considered.
KeywordsChemotherapeutic Drug Ovarian Carcinoma Cell Line Overcome Drug Resistance Target Cell Lysis Human Ovarian Carcinoma Cell Line
Unable to display preview. Download preview PDF.
- Coleman, C.N., Glove, D.J. and Turrisi, A.T. (1990) Radiation and chemotherapy sensitizers and protectors. In Cancer Chemotherapy, (eds B.A. Chabner and J.M. Collins), J.B. Lippincott, Philadelphia, pp. 424–48.Google Scholar
- 15.McGown, A.T. and Gox, B.W. (1986) A proposed mechanism of resistance to cyclophosphamide and phosphoramide mustard in a Yoshida cell line in vitro. Cancer Chemother. Pharmacol, 17,223–9.Google Scholar
- 21.Reichman, B., Markman, M., Inotti, N. et al (1989) Phase I trial of intraperitoneal recombinant tumor necrosis factor. Proc. Am. Soc. Clin. Oncol, 8,64.Google Scholar
- 22.Raeth, U., Schmid, H., Karck, U. et al (1991) Phase II trial of recombinant human tumor necrosis factor in patients with malignant ascites from ovarian carcinomas and non-ovarian tumors with intraperitoneal spread. Proc. Am. Soc. Clin. Oncol, 10, 187.Google Scholar
- 24.Schiller, J.H., Alberti, D.B., Arzoomanian, R.Z. et al (1990) Phase I trial of combination of recombinant gamma interferon and recombinant tumor necrosis factor alpha. Proc. Am. Assoc. Cancer Res., 31,183.Google Scholar
- 28.Orr, D., Oldham, R., Lewis, M. et al (1989) Phase I study of the sequenced administrationD. of etoposide and recombinant tumor necrosis factor in patients with advanced malignancy, Proc. Am. Sac. Clin. Oncol, 8, 741.Google Scholar