Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Genasense (formerly known as G-3139), an antisense oligonucleotide specific for Bcl-2, is under development by Genta as an iv drip infusion for the potential treatment of various cancers including melanoma, prostate, breast and colon cancer [3083751. It is in phase III trials for malignant melanoma, for which it has been awarded Fast Track status 1359044]. Genasense received Orphan Drug status in August 2000 [3782331. In September 2000, the company announced that pivotal phase III trials in multiple melanoma, chronic lymphocytic leukemia (CLL) and acute myelocytic leukemia (AML) would be underway by 2001 [382783]. By January 2001, trials in AML and CLL had been initiated 1396512]. As of February 2001, Genta was planning the initiation of two additional, registration quality trials. Pending positive results from these trials, launch of Genasense is anticipated in 2002 13984111. A phase III trial in patients with advanced multiple myeloma at 65 centers in the US, Canada and Great Britain began in February 2001. The trial will examine whether the addition of Genasense can improve response rates, response duration and quality of life compared with dexamethasone therapy alone 13989081. Genta Inc has been issued a patent (US-05831066) for Genasense 1283005]. The patent provides protection to Genta for the composition of Genasense and its analogs. Furthermore, Genta Inc has also been issued two new patents that cover a series of compounds containing new backbone constructions that enhance the antisense affinity of the drug to the target pre-RNA, while the other patent covers the methods for preparation of antisense oligonucleotides containing the new backbone structures 12896851. Genta has already licensed the rights for the use of Bd-2 as a target for antisense- and gene therapy-based treatments from The University of Pennsylvania. The licensing agreements with Chugai Pharmaceutical Co for worldwide marketing and profit sharing places Genta in a favorable position. In January 2001, Needham & Co expected Genasense to have a potential market of 47,700 malignant melanoma patients in the US. The analysts also expected potential patient market sizes of 50,000 (CLL), 21,000 (AML), 136,000 (non-small cell lung cancer; NSLCC) and 180,000 (prostate cancer) in the US. In addition, the analysts predicted that Genasense would be approved for melanoma in the second quarter of 2002, with approvals to follow for CLL (third quarter of 2002), AML (third quarter of 2002) and myeloma (fourth quarter of 2002) 1399251].
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PMID:Genasense (Genta Inc). 1156 20

The components of the apoptotic program are targets for anticancer therapy. Bcl-2 protein inhibits apoptosis and confers resistance to treatment with traditional cytotoxic chemotherapy, radiotherapy, and monoclonal antibodies (mAb). Oblimersen sodium (G3139, Genasense, Genta Inc., Berkeley Heights, NJ) is an antisense oligonucleotide (AS-ON) compound designed to specifically bind to the first 6 codons of the human bcl-2 mRNA sequence, resulting in degradation of bcl-2 mRNA and subsequent decrease in Bcl-2 protein translation. Oblimersen is the first oligonucleotide to demonstrate proof of principle of an antisense effect in human tumors by the documented downregulation of the target Bcl-2 protein. A growing body of preclinical and clinical evidence suggests that oblimersen synergizes with many cytotoxic and biologic/immunotherapeutic agents against a variety of hematologic malignancies and solid tumors. Randomized clinical trials are currently underway to evaluate the efficacy and tolerability of oblimersen in combination with cytotoxic chemotherapy in chronic lymphocytic leukemia, multiple myeloma, malignant melanoma, and non-small cell lung cancer. In addition, nonrandomized trials are under way to evaluate oblimersen in non-Hodgkin's lymphoma, acute myeloid leukemia, and hormone-refractory prostate cancer. Preclinical data also support the clinical evaluation of oblimersen in additional tumor types, including chronic myelogenous leukemia and breast, small cell lung, gastric, colon, bladder, and Merkel cell cancers. Enhancement of the efficacy of anticancer treatments with oblimersen Bcl-2 antisense therapy represents a promising new apoptosis-modulating strategy, and ongoing clinical trials will test this therapeutic approach.
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PMID:Oblimersen Bcl-2 antisense: facilitating apoptosis in anticancer treatment. 1216 2

The components of the apoptotic pathway are targets for anticancer therapy. Bcl-2 protein inhibits apoptosis and confers resistance to treatment with traditional cytotoxic chemotherapy, radiotherapy, and monoclonal antibodies. Oblimersen sodium (G3139, Genasense, Genta Inc, Berkeley Heights, NJ) is an antisense oligonucleotide compound designed to specifically bind to the first six codons of the human bcl-2 mRNA sequence, resulting in degradation of bcl-2 mRNA and subsequent decrease in Bcl-2 protein translation. Oblimersen is the first oligonucleotide to demonstrate proof of principle of an antisense effect in human tumors by the documented downregulation of the target Bcl-2 protein. A growing body of preclinical and clinical evidence suggests that oblimersen synergizes with many cytotoxic and biologic/immunotherapeutic agents against a variety of hematologic malignancies and solid tumors. Randomized clinical trials are currently underway to evaluate the efficacy and tolerability of oblimersen in combination with cytotoxic chemotherapy in chronic lymphocytic leukemia (CLL), multiple myeloma (MM), malignant melanoma, and non-small cell lung cancer. In addition, nonrandomized trials are underway to evaluate oblimersen in non-Hodgkin's lymphoma (NHL), acute myeloid leukemia (AML), and hormone-refractory prostate cancer. Preclinical data support the clinical evaluation of oblimersen in additional tumor types, including chronic myelogenous leukemia, and breast, small cell lung, gastric, colon, bladder (CML), and Merkel cell cancers. Enhancement of the efficacy of anticancer treatments with oblimersen Bcl-2 antisense therapy represents a promising new apoptosis-modulating strategy, and ongoing clinical trials will test this therapeutic approach.
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PMID:Oblimersen sodium (G3139 Bcl-2 antisense oligonucleotide) therapy in Waldenstrom's macroglobulinemia: a targeted approach to enhance apoptosis. 1272 Jan 57

The regulation of apoptosis is an important potential target for anticancer therapy. The mitochondrial Bcl-2 protein inhibits apoptosis and is therefore an important mediator of resistance to treatment with traditional cytotoxic chemotherapy, radiotherapy and monoclonal antibody therapy. Oblimersen (Genasense, Aventis Pharmaceuticals / Genta Inc) is a 18mer antisense-oligonucleotide (ASO), which specifically binds to the first 6 codons of the human bcl-2 mRNA, resulting in degradation and destruction of the mRNA by RNAse H. Subsequently there is a significant decrease of bcl-2 translation. A growing number of preclinical and clinical studies suggests that the combination of cytotoxic therapy with Oblimersen results in synergistic anticancer efficacy in many hematologic and solid tumors. Due to its low toxicity profile, oblimersen is an ideal combination partner with conventional chemotherapy. Three randomized phase-III trials (malignant melanoma, chronic lymphocytic leukemia, multiple myeloma) have recently finished recruitment. The results of these studies will be available by the end of 2003. Based on preclinical data, a lot of nonrandomized phase-II studies on several different tumor types like AML, CML, NHL, prostate cancer and breast cancer are underway. The manipulation of proapoptotic and antiapoptotic factors in favor of proapoptotic factors by inhibition of the bcl-2 protein translation in order to enhance the efficacy of anticancer treatments represents a promising new treatment concept in oncology.
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PMID:[Proapoptotic therapy with oblimersen (bcl-2 antisense oligonucleotide)--review of preclinical and clinical results]. 1471 45

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Know- ledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: ABI-007, Ad.Egr.TNF.11D, adefovir dipivoxil, AdPEDF.11, AES-14, albumex, alefacept, alemtuzumab, aliskiren fumarate, alvimopan hydrate, aAminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, anakinra, anti-IL-12 MAb, aprepitant, atazanavir sulfate, atrasentan, avanafil; Banoxantrone, BG-12, bimatoprost, bortezomib, bosentan; Calcipotriol/betamethasone dipropionate, caspofungin acetate, CBT-1, ciclesonide, clofarabine, conivaptan hydrochloride, CpG-7909, C-Vax, Cypher; DA-8159, DAC:GLP-1, darbepoetin alfa, darifenacin, duloxetine hydrochloride; Eculizumab, efalizumab, efaproxiral sodium, EGF vaccine, eletriptan, epratuzumab, erlotinib hydrochloride, escitalopram oxalate, ETC-642, etoricoxib, everolimus, exenatide; Gefitinib, IV gamma-globulin; Human insulin, gamma-hydroxybutyrate sodium; IDN-6556, iguratimod, imatinib mesylate, indiplon, ixabepilone; Laquinimod, LB-80380, lidocaine/prilocaineliraglutide, lopinavir, lopinavir/ritonavir, lucinactant; MAb-14.18, melatonin, MLN-591-DM1; NC-531, neridronic acid, nesiritide, neutrophil-inhibitory factor, niacin/lovastatin; Oblimersen sodium, olcegepant, oral Insulin, ORV-105; Palonosetron hydrochloride, PAmAb, pegaptanib sodium, peginterferon alfa-2a, pegvisomant, perifosine, pexelizumab, phenoxodiol, phenserine tartrate, pimecrolimus, pramlintide acetate, pregabalin, PRO-542, prostate cancer vaccine, PT-141; Ramelteon, rasagiline mesilate, rDNA insulin, reslizumab, rh-Lactoferrin, ribamidine hydrochloride, rosuvastatin calcium; S-8184l, SC-1, sorafenib, St. John's Wort extract, SU-11248; Taxus, telbivudine, tenofovir disoproxil fumarate, teriparatide, testosterone gel, tezosentan disodium, tipifarnib, tolvaptan, trabectedin, travoprost, travoprost/timolol, treprostinil sodium; Vardenafil hydrochloride hydrate; Xcellerated T cells, XR-5944; Yttrium 90 (90Y) ibritumomab tiuxetan; Ziconotide.
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PMID:Gateways to clinical trials. 1534 41

Expression of the proto-oncogene Bcl-2 is associated with tumor progression. Bcl-2's broad expression in tumors, coupled with its role in resistance to chemotherapy and radiation therapy-induced apoptosis, makes it a rational target for anticancer therapy. Antisense Bcl-2 oligodeoxynucleotide (ODN) reagents have been shown to be effective in reducing Bcl-2 expression in a number of systems. We investigated whether treating human prostate cancer cells with antisense Bcl-2 ODN (G3139, oblimersen sodium, Genasense) before irradiation would render them more susceptible to radiation effects. Two prostate cancer cell lines expressing Bcl-2 at different levels (PC-3-Bcl-2 and PC-3-Neo) were subjected to antisense Bcl-2 ODN, reverse control (CTL), or mock treatment. Antisense Bcl-2 ODN alone produced no cytotoxic effects and was associated with G(1) cell cycle arrest. The combination of antisense Bcl-2 ODN with irradiation sensitized both cell lines to the killing effects of radiation. Both PC-3-Bcl-2 and PC-3-Neo xenografts in mice treated with the combination of antisense Bcl-2 ODN and irradiation were more than three times smaller by volume compared with xenografts in mice treated with reverse CTL alone, antisense Bcl-2 ODN alone, irradiation alone, or reverse CTL plus radiotherapy (P = 0.0001). Specifically, PC-3-Bcl-2 xenograft tumors treated with antisense Bcl-2 ODN and irradiation had increased rates of apoptosis and decreased rates of angiogenesis and proliferation. PC-3-Neo xenograft tumors had decreased proliferation only. This is the first study which shows that therapy directed at Bcl-2 affects tumor vasculature. Together, these findings warrant further study of this novel combination of Bcl-2 reduction and radiation therapy, as well as Bcl-2 reduction and angiogenic therapy.
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PMID:Knock-down of Bcl-2 by antisense oligodeoxynucleotides induces radiosensitization and inhibition of angiogenesis in human PC-3 prostate tumor xenografts. 1723 70