Characterization of Treatment Response to Recombinant Interferon-a2b in Osteosarcoma Xenografts

Abstract

Interferons (IFNs) may target cancer cells both through their regulation of the immune response, effect on angiogenesis and through direct effect on cancer cells. Treatment response has been demonstrated in osteosarcoma patients, but tumour resistance to IFN-α is common. Hence, understanding the molecular mechanisms involved in response and resistance is essential for improving therapeutic efficacy. Of five xenografts screened for specific growth delay in response to treatment with unconjugated and PEGylated IFN-α2b, one displayed growth inhibition and tumour shrinkage. Growth inhibition increased on a dosing schedule of PEGylated IFN every third day. Xenografts resistant to PEGylated IFN were similarly resistant to unconjugated IFN. Combination treatment with IFN-α2b and doxorubicin resulted in improved growth control rates. Transcriptional profiling analysis of the one sensitive and two resistant xenografts identified a common set of 79 genes significantly affected by IFN-α2b treatment independent of tumour growth inhibition. All but four of the 79 genes were up-regulated. The majority of these genes were well characterized IFN-stimulated genes and core members of the IFN-α signalling pathway. The expression of a set of 128 unique genes changed only in the sensitive xenograft; 52/128 genes were up-regulated. The specific geneexpression pattern seen in the responsive xenograft identified possible pathways important for the antitumor effect of IFN-α in osteosarcoma, including ssubsets of genes involved in cell adhesion and osteogenic tissue development. The observed improved control rates of combined treatment with IFN and doxorubicin are encouraging and should be further explored.

Vaccine Potentiality and Stem Cells Enhancing Cure to Cancer

“…Interactions initiate the classical HJanus kinaseH-STAT (HJAK-STATH) signalling pathway, whereas the early studies were performed with mixtures of IFNs extracted from white blood cells, most clinical trials have been performed with single-species recombinant IFN-a, and more recently with variants conjugated to poly-ethylene-glycol (PEGylation). PEGylation delays the elimination of IFN, allowing for once weekly treatment in humans and carries a promise of higher efficacy and reduced toxicity Although IFN is in some clinical use in advanced osteosarcoma, the relative contributions of direct antitumour effects, inhibition of angiogenesis and indirect immune-mediated effects are not known [33]. Metastasis a cure induced for the breast cancer regulates PTEN (phosphatase tensin) protein.…”

Role of Tumor Suppressor Protein p53 in Apoptosis and Cancer Therapy

“…It seems that radiotherapy or chemoradiation can be appropriate alternative to total laryngectomy in laryngeal cancers [23]. Treatment with IFN and doxorubicin has been demonstrated in osteosarcoma patients, but tumour resistance to IFN-a is common [24]. Lymphangiomas is also a type of cancer for this surgical resection still remains the best treatment for lymphangiomas; other treatment options, such as sclerotherapy have been proposed as an alternative to reduce the impact and complications of surgery [25].…”

A Compendium of Cancer Therapeutic Strategies and their Modality

“…These can be made in the laboratory and used to shrink or stop the growth of cancer cells. Some interferon's stimulate the growth of lymphocytes which then destroys the cancer cells [66,67]. The side effects with this include fever, chills, muscle and joint aches, and fatigue.…”