Odies (Figure 1). Similar selectivity for tumor cells was observed in vivo. FTI treatment of mice for as little as three days eliminated > 90 of the tumor cells, while only slightly affecting the normal lymphocyte populations in the same mice (Figures 2, 3, and 4). When mice without tumors were treated with L-744,832 for as long as 28 days, no significantPage 9 of(page number not for citation purposes)Molecular Cancer 2008, 7:http://www.molecular-cancer.com/content/7/1/strated that L-744,832 could prevent the formation of diffuse large B cell splenic lymphomas in mice that expressed an activated PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/25645579 N-Ras oncogene under the MMTV promoter [8]. L-744,832 has also been shown to cause regression of mammary and salivary tumors in mice expressing MMTVv-H-Ras alone [45], or together with MMTV- c-Myc [7]. Unlike the above transgenic tumor models, the murine lymphoma studied here does not contain an activated Ras transgene but may express a spontaneously activated Ras allele. Such mutations are not commonly found in B cell non-Hodgkin lymphomas in humans [46], however, we cannot rule out that a spontaneous mutation occurred at one of the Ras alleles L 663536 cost during the process of tumorigenesis in our mouse model. FTIs have mixed results with other mouse tumors that are not known to harbor Ras mutations. For example, the mammary tumors in MMTV- cNeu mice do not respond to L-744,832 [7], but the pre-Bcell leukemia in BCR/Abl transgenic mice regressed upon treatment with SCH66336 [21]. Our results are consistent with other models that do not use Ras mutations as an initiating tumorigenic event but have shown that FTI treatment can still effectively block tumor growth.Implications for treatment of human B cell lymphomas Our preclinical results with this mouse lymphoma model indicate that patients with mature B cell lymphomas should be considered for inclusion in FTI clinical trials. One of the important features of this mouse model is the self-reactivity of the transformed B cells. Although FTIs do not appear to block proliferation of nontransformed B cells in response to antigen receptor stimulation, these drugs were able to block proliferation and induce cell death in the self-reactive transformed B cells. Antigen receptor activation by self or environmental antigens may contribute the generation of certain B cell malignancies in humans [35]. Recognition of autoantigens or foreign antigens from a chronic infection appears to be an important feature of a substantial fraction of B cell chronic lymphocytic leukemias [47,48], follicular lymphomas [49], and certain other leukemias and lymphomas [35]. We suggest that FTIs may be able to block the proliferation of BCR-expressing B cell lymphomas by interfering with the antigen receptor and/or cytokine signaling pathways within the transformed cells.likely to harbor activating Ras mutations, such as pancreatic cancer. However, subsequent experience has led to the inclusion of many additional patient groups in FTI clinical trials. For example, SCH66336 is undergoing a phase III clinical trial on myelodysplastic syndrome and chronic myelomonocytic leukemia (Study ID P02978). However, mature B cell lymphomas, such as Burkitt’s, are not specifically targeted in any of the current FTI clinical trials, perhaps because of the high success rate of current therapies for Burkitt’s lymphoma. Treatment of Burkitt’s lymphoma typically involves a combination of chemotherapies: cyclophosphamide, etoposide, vincristine, bleomycin, d.