Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Monoclonal antibody-based therapeutics are beginning to realize the promise that was predicted with the advent of the core technology more than 20 years ago. Antibody-based therapeutics targeting tumor cell surface antigens such as B-cell idiotypes, CD20 on malignant B cells, CD33 on leukemic blasts, and HER2/neu on breast cancer cells have shown efficacy in clinical trials. Multiple antibody-based strategies have shown promising efficacy in recent clinical trials. Unconjugated immunoglobulins directed against CD20 induce partial and complete responses in up to 50% of patients with advanced, indolent non-Hodgkin's lymphoma When such antibodies are conjugated to appropriate radionuclides and administered in therapeutic doses, the proportions of complete and overall responses increase considerably. Conjugates composed of anti-CD33 antibodies and the chemotherapy agent, calicheamicin, show promising activity in patients with relapsed or refractory acute myelogenous leukemia. Treatment of patients with advanced breast cancer using the anti-HER2/neu antibody trastuzumab (Herceptin; Genentech, San Francisco) leads to objective responses in some patients whose tumors overexpress the HER2/neu oncoprotein. These exciting results justify recent enthusiasm for continued efforts to refine existing approaches and to develop new antibody-based strategies to treat human malignancy.
 ...
PMID:An overview of monoclonal antibody therapy of cancer. 1048 93

Monoclonal antibody therapy is beginning to realize its promise. Efficacy has been seen in clinical trials using antibodies that target tumor cell surface antigens such as B-cell idiotypes, CD20 on malignant B cells, CD33 on leukemic blasts, and HER2/neu on breast cancer. Unconjugated immunoglobulins directed against CD20 induce partial and complete responses in up to 50% of patients with advanced, indolent non-Hodgkin's lymphoma. When such antibodies are conjugated to radionuclides, complete and overall response rates increase. Conjugates composed of anti-CD33 antibodies and the chemotherapy agent, calicheamicin, show promising activity in patients with relapsed or refractory acute myelogenous leukemia Treatment of patients with advanced breast cancer using the anti-HER2/neu antibody, trastuzumab (Herceptin; Genentech, San Francisco, CA) leads to objective responses in some patients with overexpression of the HER2/neu oncoprotein. These exciting results provide a basis for further refinement of the existing approaches to develop new antibody-based cancer therapy strategies.
 ...
PMID:Monoclonal antibody therapy of cancer. 1056 Oct 17

Despite testing since the mid-1900s, only in the past three years have some monoclonal antibodies provided sufficient efficacy and safety data to support regulatory approval as cancer therapy. Adjuvant-edrecolomab monoclonal antibody was approved in Germany after demonstration of a statistically significant 32% improvement over observation alone in the seven-year mortality rate for patients with colorectal cancer. Similarly, trastuzumab monoclonal antibody combined with chemotherapy prolonged the median time to the progression of breast cancer compared to chemotherapy alone. Unconjugated monoclonal antibodies investigated for the treatment of hematologic malignancies include anti-idiotype, CAMPATH-1, and rituximab. Rituximab was the first such therapy approved in the United States for relapsed or refractory low-grade or follicular B-cell non-Hodgkin's lymphoma after demonstration of an overall response rate of 48% and a duration of response of 11.7 months. The radioisotope-conjugated monoclonal antibodies tested as therapy include anti-B1, LYM-1, LL2, anti-CD33, and ibritumomab tiuxetan. Clearly, the full potential of immunotherapy still lies ahead.
 ...
PMID:Antibody-targeted immunotherapy for treatment of malignancy. 1116 Jul 71

Monoclonal antibodies (MAbs) have been used as therapeutic agents for many years. In 1997, Rituxan (IDEC-C2B8, rituximab, MabThera) became the first MAb to be approved by the FDA for a cancer indication. Rituxan served to heighten interest in the therapeutic applications of MAbs. Herceptin (for patients with breast cancer) and Mylotarg (for patients with acute myeloid leukemia) were approved shortly thereafter. Literally dozens of antibodies are currently under investigation for a variety of malignant and non-neoplastic indications. Rituxan is effective in patients with low-grade or follicular, relapsed or refractory non-Hodgkin's lymphoma (NHL). The response rate and time to progression (responders) are in the 50% and 13 months range, respectively. It is also active in intermediate-grade NHL where a large randomized study, in combination with CHOP chemotherapy, has shown a statistically significant increase in complete response (CR) rate (75% vs. 60%), prolongation of 1 year event-free survival (69% vs. 49%) and of overall survival (83% vs. 68%) as compared to CHOP alone. This marks the first time that any agent has shown results superior to CHOP, the curative gold standard for this type of NHL. Other promising antibodies under clinical investigation include: Hu1D10; Anti CD19, 22, 52, and anti-Id antibodies. The safety profile, clinical activity, and mechanism of action of these MAbs make them ideal candidates for combination with chemotherapy or biologicals. Over the next few years, we will see very significant therapeutic advances emerge as this important research yields additional clinical results.
 ...
PMID:Monoclonal antibodies: a new era in the treatment of non-Hodgkin's lymphoma. 1176 12

Monoclonal antibodies used in the treatment of cancer are discussed. Monoclonal antibodies are a new class of agents targeted at specific receptors on cancer cells. In addition to having direct cellular effects, antibodies can carry substances, such as radioactive isotopes, toxins, and antineoplastic agents, to the targeted cells. Five monoclonal antibodies--rituximab, trastuzumab, gemtuzumab ozogamicin, alemtuzumab, and ibritumomab tiuxetan--are available for clinical use. Rituximab is active against indolent lymphomas, providing a valuable alternative for patients with relapsed or refractory disease. Rituximab plus cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP) increased survival over CHOP alone in patients with high-grade lymphomas. Trastuzumab has significant activity against HER-2-positive breast cancer, especially in combination with paclitaxel or an anthracycline and cyclophosphamide. Gemtuzumab ozogamicin is an active second-line therapy in older patients with acute myelogenous leukemia, but its role in combination regimens is unclear. Alemtuzumab is a valuable option for salvage therapy of patients with chronic lymphocytic leukemia. Ibritumomab tiuxetan delivers radioactive isotopes to tumor cells and is active against indolent lymphomas in patients who have relapsed after chemotherapy or rituximab therapy. The most common adverse effects of monoclonal antibodies are myelosuppression, infusion-related reactions, and hypersensitivity reactions. Rituximab may cause tumor lysis syndrome, arrhythmias, and pulmonary dysfunction. Alemtuzumab causes immunosuppression, increasing the risk of infection. Gemtuzumab ozogamicin may cause hepatotoxicity, and trastuzumab may cause significant pulmonary or cardiac toxicity. Investigational monoclonal antibodies include edrecolomab and tositumomab. Monoclonal antibodies have a significant role in the management of patients with advanced refractory or relapsed lymphomas and leukemias.
 ...
PMID:Monoclonal antibodies in the treatment of cancer, Part 1. 1295 53

Monoclonal antibodies used in the treatment of cancer are discussed. Monoclonal antibodies are a new class of agents targeted at specific receptors on cancer cells. In addition to having direct cellular effects, antibodies can carry substances, such as radioactive isotopes, toxins, and antineoplastic agents, to the targeted cells. Five monoclonal antibodies--rituximab, trastuzumab, gemtuzumab ozogamicin, alemtuzumab, and ibritumomab tiuxetan--are available for clinical use. Rituximab is active against indolent lymphomas, providing a valuable alternative for patients with relapsed or refractory disease. Rituximab plus cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP) increased survival over CHOP alone in patients with high-grade lymphomas. Trastuzumab has significant activity against HER-2-positive breast cancer, especially in combination with paclitaxel or an anthracycline and cyclophosphamide. Gemtuzumab ozogamicin is an active second-line therapy in older patients with acute myelogenous leukemia, but its role in combination regimens is unclear. Alemtuzumab is a valuable option for salvage therapy of patients with chronic lymphocytic leukemia. Ibritumomab tiuxetan delivers radioactive isotopes to tumor cells and is active against indolent lymphomas in patients who have relapsed after chemotherapy or rituximab therapy. The most common adverse effects of monoclonal antibodies are myelosuppression, infusion-related reactions, and hypersensitivity reactions. Rituximab may cause tumor lysis syndrome, arrhythmias, and pulmonary dysfunction. Alemtuzumab causes immunosuppression, increasing the risk of infection. Gemtuzumab ozogamicin may cause hepatotoxicity, and trastuzumab may cause significant pulmonary or cardiac toxicity. Investigational monoclonal antibodies include edrecolomab and tositumomab. Monoclonal antibodies have a significant role in the management of patients with advanced refractory or relapsed lymphomas and leukemias.
 ...
PMID:Monoclonal antibodies in the treatment of cancer, Part 2. 1296 6

Trastuzumab (Herceptin) Fab were prepared by digestion of intact IgG with immobilized papain, derivatized with diethylenetriaminepentaacetic acid (DTPA) and radiolabeled with (111)In. The dissociation constant (Kd) for binding of Fab to HER2/neu-positive SK-BR-3 human breast cancer cells was two- to threefold higher than for intact IgG (14-36 vs. 8-14 nM). The binding affinity was not significantly decreased after DTPA derivatization (Kd=47 nM). (111)In-trastuzumab Fab localized specifically in HER2/neu-positive BT-474 human breast cancer xenografts in athymic mice with tumor uptake of 7.8+/-0.7% injected dose (ID)/g and tumor/blood ratio of 25.2+/-1.6 at 72 h postinjection compared with 2.7+/-0.7% ID/g and 7.0+/-0.9 for (111)In-HuM195 anti-CD33 Fab (significantly different, P<.001). Small (3-5 mm in diameter) BT-474 tumors were imaged with (111)In-trastuzumab Fab as early as 24 h postinjection.
 ...
PMID:Imaging of HER2/neu-positive BT-474 human breast cancer xenografts in athymic mice using (111)In-trastuzumab (Herceptin) Fab fragments. 1569 61

Gateways to Clinical Trials are 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 Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com.This issue focuses on the following selection of drugs: ABT-263, AC-2307, Aclidinium bromide, Adefovir dipivoxil, ADH-1, Agatolimod sodium, Alefacept, Aliskiren fumarate, Aminolevulinic acid methyl ester, Anakinra, Apaziquone, Aprepitant, Aripiprazole, ASM-8, Atiprimod hydrochloride, AVE-0277, AVE-1642, AVE-8062, Axitinib, Azacitidine, AZD-0530; Bazedoxifene acetate, Bevacizumab, Bexarotene, BI-2536, Biphasic insulin aspart, BMS-387032, BMS-663513, Bortezomib, BQ-123, Brivanib alaninate, BSI-201; Caspofungin acetate, CDX-110, Cetuximab, Ciclesonide, CR-011, Cypher; Daptomycin, Darbepoetin alfa, Dasatinib, Decitabine, Deferasirox, Denosumab, Dexlansoprazole, Dexmethylphenidate hydrochloride, DNA-Hsp65 vaccine, Dovitinib, Drotrecogin alfa (activated), DTaP-HBV-IPV/Hibvaccine, DTaP-IPV-HB-PRP-T, Duloxetine hydrochloride, Dutasteride; Ecogramostim, Elacytarabine, Emtricitabine, Endothelin, Entecavir, Eplivanserin fumarate, Escitalopram oxalate, Everolimus, Ezetimibe, Ezetimibe/simvastatin; Farletuzumab, Fesoterodine fumarate, Fibrin sealant (human), Fulvestrant; Gefitinib, Gemtuzumab ozogamicin, Glufosfamide, GSK-1562902A; Hib-TT; Imatinib mesylate, IMC-11F8, Imidazoacridinone, IMP-321, INCB-18424, Indiplon, Indisulam, INNO-406, Irinotecan hydrochloride/Floxuridine, ITF-2357, Ixabepilone; KRN-951; Lasofoxifene tartrate; Lenalidomide, LGD-4665, Lonafarnib, Lubiprostone, Lumiliximab; MDX-1100, Melan-A/MART-1/gp100/IFN-alfa, Methyl-CDDO, Metreleptin, MLN-2704, Mycophenolic acid sodium salt; Na-ASP-2, Naproxcinod, Nilotinib hydrochloride monohydrate, NPI-2358; Oblimersen sodium, Odanacatib; Paclitaxel nanoparticles, PAN-811, Panobinostat, PBI-1402, PC-515, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Perillyl alcohol, Perphenazine 4-aminobutyrate, PeviPRO/breast cancer, PF-03814735, PHA-739358, Pimecrolimus, Plitidepsin, Posaconazole, Prasterone, Prasugrel, Pregabalin, Prucalopride, PRX-08066; rAAV2-TNFR:Fc, Ranelic acid distrontium salt, Ranibizumab, rCD154-CLL, Retapamulin, RTS,S/SBAS2, rV-PSA-TRICOM/rF-PSA-TRICOM; SG-2000, Sinecatechins, Sirolimus-eluting stent, Sorafenib, SP-1640, Strontium malonate, Succinobucol, Sunitinib malate; Taxus, Teduglutide, Telavancin hydrochloride, Telbivudine, Telmisartan/hydrochlorothiazide, Tenofovir disoproxil fumarate, Tenofovir disoproxil fumarate/emtricitabine, Tocilizumab; Ustekinumab; V-5 Immunitor, Voriconazole, Vorinostat; Xience V, XL-184, XL-647, XL-765; Y-39983, Zibotentan.
 ...
PMID:Gateways to clinical trials. 1898 83

Antibody-drug conjugates (ADCs) are becoming an increasingly important sub-class of antibody-related therapeutics. Two ADCs, brentuximab vedotin (Adcetris) and ado-trastuzumab emtansine (Kadcyla), were recently approved for marketing both by the US Food and Drug Administration (FDA) and the European Medicine Agency (EMA). Brentuximab vedotin is marketed as therapy for hematological malignancies (Hodgkin lymphoma, systemic anaplastic large cell lymphoma), while ado-trastuzumab emtansine is marketed for treatment of a solid tumor (breast cancer). The approvals of these two ADCs followed the mitigated success of gemtuzumab ozogamicin (Mylotarg), which was withdrawn from the US market in 2010, ten years after approval by the FDA.
 ...
PMID:Antibody-drug conjugates: present and future. 2442 77

Rituximab, a monoclonal antibody (MAb) against CD20, was the first MAb approved by the US Food and Drug Administration (FDA) for treatment of B cell non-Hodgkin lymphoma (B-NHL). Conjugating toxins to MAb was a technical challenge; however, with improvements in linker technology, immunoconjugates were constructed and revolutionized cancer treatment. Gemtuzumab ozogamicin was the first antibody drug conjugate (ADC) approved by the FDA. Because of the success of brentuximab vedotin and ado-trastuzumab emtansine in treating Hodgkin lymphoma (HL) and HER2-positive breast cancer, respectively, newer ADCs are being investigated. Brentuximab vedotin is approved for both HL and anaplastic large cell lymphoma. Newer ADCs, such as polatuzumab vedotin (targeting CD79b), pinatuzumab vedotin (targeting CD22), inotuzumab ozogamicin (targeting CD19), SAR3419 (targeting CD19), IMGN529 (targeting CD37), and SGN-CD19A (targeting CD19), have shown promising preclinical and early clinical activity. These findings will change the landscape of B-NHL treatment away from age-old "CHOP"-based chemotherapies.
...
PMID:Development and Integration of Antibody-Drug Conjugate in Non-Hodgkin Lymphoma. 2619 24


1 2 Next >>