2DG-ABT Combination Therapy afternoon, and Group E mice received a glucose/deoxyglucose mix in the morning and ABT-263 in the afternoon. After treatment with 2DG only, there was only a 5- to 6-day delay in tumor growth (Fig. 7a). In contrast, except for one mouse in Group E, the tumors in all of the mice in Groups C, D, and E regressed during treatment. The rates of tumor regression among these groups were roughly similar. However, when treatments were concluded at day 27, tumors began to grow in mice in Groups C and D, such that all these mice required euthanasia before day 50. The mice in Group E fared better, and most of their tumors remained small until day 50; these mice survived an average of 2 weeks longer than the mice in Groups C and D (Fig. 7b). The mouse experiments were repeated twice with very similar results (Fig. S6). These results concur with our tissue culture results, demonstrating the clear advantage of the combination treatment. When we surveyed literature on treat- ments of PPC-1/PC-3 tumor bearing mice, we only found treatments that had arrested or slowed tumor growth (cytostatic effects) – and we alone had the treatment to induce tumor regression (cytoxic effect) [27,55,56,57,58,59]. To summarize, these preclinical data suggest that deoxyglucose-ABT-263/737 combination therapy may provide a safe and effective alternative to the genotoxin-based chemotherapies currently used for treatment of cancer. Discussion In order to induce apoptosis in cancer cells, genotoxin-based therapies activate cell cycle checkpoint and genomic surveillance programs. Rapidly dividing cancer cells are also under pressure to compromise those same programs. As cancer progresses and accumulates more mutations, it seems natural that it becomes more resistant to genotoxin-based therapies. Therefore, to effectively treat advanced cancers, we need a different approach. Uncontrolled cell growth is one of the defining features of cancer. Indeed, most cancer cells have multiple mutations in the Figure 7. Treatment of tumor-bearing mice with 2DG-ABT combination. Five million PPC-1 human prostate cancer cells were xenografted onto nude mice as described in the text and the method. a, Mice Tumor volumes were measured in mice (n = 7 per group) treated with diluent only (group A), 2DG (group B), ABT-263 (group C), 2DG plus ABT-263 (group D), or 2DG mixed with D-glucose plus ABT-263 (group E), as explained in the text, where drugs were administered 3 times weekly between day 9 and 27 (gray rectangles). b, Survival of tumor-bearing mice was determined at various times post-inoculation with PPC-1 cells. The % of surviving mice is indicated from groups A-E (n = 7 per group). The difference of survival days between Group C & D versus Group E is p = 0.0283, 95% confidence interval of this difference: from 220.98 to 21.36 by unpaired t-test. doi:10.1371/journal.pone.0024102.g007 PLoS ONE | www.plosone.org 9 September 2011 | Volume 6 | Issue 9 | e24102