Well, where are we going in the future

Well, where are we going in the future? I think where we are going in the future for sarcomas is further dose intensification with growth factor and stem cell support. Possibly reversing multi-drug resistance, like for Adriamycin, with PSC-833 and Incel. Possibly angiogenesis inhibitors to reduce the chances of metastasis. New work done in hormonal growth manipulation, one out of the Dana Farber. Dr. Dimitri looking at the peroxisome proliferator activating receptor gammon. It’s a ligand. Troglitazone is a ligand for this receptor which is an antidiabetic drug. Stimulating this receptor causes terminal differentiation of lipocytes and it may be helpful in inducing adipose differentiation. At the NCI a somatostatin analog, somatuline, is being looked at. This blocks the release of growth hormone which decreases the production of insulin-like growth factor 1, which is a growth factor for osteogenic sarcoma, and which is being looked at in the adjuvant setting. Also, as I mentioned, the work at Memorial with the possible use now of Herceptin in those osteogenic sarcoma patients who are HER2/neu positive, to possibly use in conjunction with platinum. Immune-modulation; worked on by Dr. Kleineman at the M.D. Anderson. LMTPE is one of the smallest components of the microbacterium and this causes stimulation of the pulmonary macrophages and in both a murine and a human model has … she has shown that there has been a reduction in the incidence of lung metastasis and a decrease in lung metastasis. So the intergroup, pediatric group now – which is the CCSG plus POG – is looking at the use of this agent after the patients have received adjuvant chemotherapy in osteogenic sarcoma. Possible use of immunotoxins. Our group and the NIHLBI are looking at the use of non-myeloablative allogeneic transplant. In other words, giving a somewhat lower dose chemotherapy regimen of Cytoxan and fludarabine in those patients who have a relative who is an HLA match. And in terms of giving them then their relative’s marrow, and in hopes of in addition to giving their relative’s stem cells back to them, also lymphocytes and in hopes of inducing a graft-versus-tumor response. This has already been tried now in renal cell and has been presented at the ASCO and they have some very high quality responses, specifically for renal cell. We have chosen sarcomas as well because they appear to have MHC class I and II antigens and HLA antigens where you may be able to induce an immune response.

Also utilizing oncogene products, modifying tumor suppresser genes, antisense oligonucleotides, using the fusion genes that I showed you earlier as molecular markers and possibly developing vaccines to some of these tumor-specific fusion peptides. And that’s work that’s being done at the pediatric branch at the NCI.

Well, in conclusion I want to emphasize that in order to advance the goals of local tumor control, limb-salvage with optimal function, to minimize treatment morbidity, and also to improve long term survival with the goal of maximum cure; that for the sarcomas because they are so rare and because they involve so many different disciplines, it’s really important if possible to have a multi-disciplinary team approach to treat these patients.

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