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Glembatumumab
Glembatumumab vedotin (also known as CDX-011 and CR011-vcMMAE) is an antibody-drug conjugate (ADC) that targets cancer cells expressing transmembrane glycoprotein NMB (GPNMB). In May 2010, the U.S FDA granted Fast Track designation to CDX-011 for the treatment of advanced, refractory, or resistant GPNMB-expressing breast cancer. Structure and mechanism The fully human IgG2 monoclonal antibody glembatumumab (CR011) is linked to monomethyl auristatin E (MMAE). It uses a valine-citrulline enzyme-cleavable linker. The linkage is stable in the bloodstream. The antibody binds to GPNMB on the cancer cells, the ADC is internalised, the linkage is broken and MMAE is released to kill the cell. In preclinical studies glembatumumab vedotin was capable of killing GPNMB expressing melanoma and breast cancer cells ''in vitro'' and inducing partial or complete regression of GPNMB-expressing tumors in mouse models. Development Glembatumumab vedotin was in development through April 2018 by ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Glembatumumab
Glembatumumab vedotin (also known as CDX-011 and CR011-vcMMAE) is an antibody-drug conjugate (ADC) that targets cancer cells expressing transmembrane glycoprotein NMB (GPNMB). In May 2010, the U.S FDA granted Fast Track designation to CDX-011 for the treatment of advanced, refractory, or resistant GPNMB-expressing breast cancer. Structure and mechanism The fully human IgG2 monoclonal antibody glembatumumab (CR011) is linked to monomethyl auristatin E (MMAE). It uses a valine-citrulline enzyme-cleavable linker. The linkage is stable in the bloodstream. The antibody binds to GPNMB on the cancer cells, the ADC is internalised, the linkage is broken and MMAE is released to kill the cell. In preclinical studies glembatumumab vedotin was capable of killing GPNMB expressing melanoma and breast cancer cells ''in vitro'' and inducing partial or complete regression of GPNMB-expressing tumors in mouse models. Development Glembatumumab vedotin was in development through April 2018 by ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
GPNMB
Transmembrane glycoprotein NMB is a protein that in humans is encoded by the ''GPNMB'' gene. Two transcript variants encoding 560 and 572 amino acid isoforms have been characterized for this gene in humans. The mouse and rat orthologues of GPNMB are known as DC-HIL and Osteoactivin (OA), respectively. GPNMB is a type I transmembrane glycoprotein which shows homology to the pmel17 precursor, a melanocyte-specific protein. GPNMB has been reported to be expressed in various cell types, including: melanocytes, osteoclasts, osteoblasts, dendritic cells, and it is overexpressed in various cancer types. In melanocytic cells and osteoclasts the GPNMB gene is transcriptionally regulated by Microphthalmia-associated transcription factor. Function In osteoblast progenitor cells, Osteoactivin works as a positive regulator of osteoblast differentiation during later stages of matrix maturation and mineralization that is mediated at least in part by Bone_morphogenetic_protein_2 in a SMAD1 dep ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Transmembrane Glycoprotein NMB
Transmembrane glycoprotein NMB is a protein that in humans is encoded by the ''GPNMB'' gene. Two transcript variants encoding 560 and 572 amino acid isoforms have been characterized for this gene in humans. The mouse and rat orthologues of GPNMB are known as DC-HIL and Osteoactivin (OA), respectively. GPNMB is a type I transmembrane glycoprotein which shows homology to the pmel17 precursor, a melanocyte-specific protein. GPNMB has been reported to be expressed in various cell types, including: melanocytes, osteoclasts, osteoblasts, dendritic cells, and it is overexpressed in various cancer types. In melanocytic cells and osteoclasts the GPNMB gene is transcriptionally regulated by Microphthalmia-associated transcription factor. Function In osteoblast progenitor cells, Osteoactivin works as a positive regulator of osteoblast differentiation during later stages of matrix maturation and mineralization that is mediated at least in part by Bone_morphogenetic_protein_2 in a SMAD1 de ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Triple Negative Breast Cancer
Triple-negative breast cancer (TNBC) is any breast cancer that lacks or show low levels of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) overexpression and/or gene amplification (i.e. the tumor is negative on all three tests giving the name ''triple-negative''). Triple-negative is sometimes used as a surrogate term for basal-like. Triple-negative breast cancer comprises 15–20% of all breast cancer cases and affects more young women or women with a mutation in the BRCA1 gene than other breast cancers. Triple-negative breast cancers comprise a very heterogeneous group of cancers. TNBC is the most challenging breast cancer type to treat. Hormone therapy that is used for other breast cancers does not work for TNBC. In its early stages, the cancer is typically treated through surgery, radiation and chemotherapy. In later stages where surgery is not possible or the cancer has spread from the initial localised area, treatment ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
National Cancer Institute
The National Cancer Institute (NCI) coordinates the United States National Cancer Program and is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. The NCI conducts and supports research, training, health information dissemination, and other activities related to the causes, prevention, diagnosis, and treatment of cancer; the supportive care of cancer patients and their families; and cancer survivorship. NCI is the oldest and has the largest budget and research program of the 27 institutes and centers of the NIH ($6.9 billion in 2020). It fulfills the majority of its mission via an extramural program that provides grants for cancer research. Additionally, the National Cancer Institute has intramural research programs in Bethesda, Maryland, and at the Frederick National Laboratory for Cancer Research at Fort Detrick in Frederick, Maryland. The NCI receives more than in funding each ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Antibody-drug Conjugates
Antibody-drug conjugates or ADCs are a class of biopharmaceutical drugs designed as a targeted therapy for treating cancer. Unlike chemotherapy, ADCs are intended to target and kill tumor cells while sparing healthy cells. As of 2019, some 56 pharmaceutical companies were developing ADCs. ADCs are complex molecules composed of an antibody linked to a biologically active cytotoxic (anticancer) payload or drug. Antibody-drug conjugates are an example of bioconjugates and immunoconjugates. ADCs combine the targeting properties of monoclonal antibodies with the cancer-killing capabilities of cytotoxic drugs, designed to discriminate between healthy and diseased tissue. Mechanism of action An anticancer drug is coupled to an antibody that targets a specific tumor antigen (or protein) that, ideally, is only found in or on tumor cells. Antibodies attach themselves to the antigens on the surface of cancerous cells. The biochemical reaction that occurs upon attaching triggers a signal ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Capecitabine
Capecitabine, sold under the brand name Xeloda among others, is a chemotherapy medication used to treat breast cancer, gastric cancer and colorectal cancer. For breast cancer it is often used together with docetaxel. It is taken by mouth. Common side effects include abdominal pain, vomiting, diarrhea, weakness, and rashes. Other severe side effects include blood clotting problems, allergic reactions, heart problems such as cardiomyopathy, and low blood cell counts. It is not recommended in people with kidney problems. Use during pregnancy may result in harm to the fetus. Capecitabine, inside the body, is converted to 5-fluorouracil (5-FU) through which it acts. It belongs to the class of medications known as fluoropyrimidines, which also includes 5-FU and tegafur. Capecitabine was patented in 1992 and approved for medical use in 1998. It is on the World Health Organization's List of Essential Medicines. Medical uses It is used in the treatment of the following cancers: * Co ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Accelerated Approval
The United States Food and Drug Administration (FDA) initiated the FDA Accelerated Approval Program in 1992 to allow faster approval of drugs for serious conditions that fill an unmet medical need. The faster approval relies on use of surrogate endpoints In clinical trials, a surrogate endpoint (or surrogate marker) is a measure of effect of a specific treatment that may correlate with a ''real'' clinical endpoint but does not necessarily have a guaranteed relationship. The National Institutes of He .... Drug approval typically requires clinical trials with endpoints that demonstrate a clinical benefit, such as increased survival for cancer patients. Drugs with accelerated approval can initially be tested in clinical trials that use a surrogate endpoint, or something that is thought to predict clinical benefit. Surrogate endpoints typically require less time, and in the case of a cancer patient, it is much faster to measure a reduction in tumor size, for example, than overall patient ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Progression-free Survival
Progression-free survival (PFS) is "the length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse". In oncology, PFS usually refers to situations in which a tumor is present, as demonstrated by laboratory testing, radiologic testing, or clinically. Similarly, "disease-free survival" is the length of time after patients have received treatment and have no detectable disease. Time to progression (TTP) does not count patients who die from other causes but is otherwise a close equivalent to PFS (unless there are many such events). The FDA gives separate definitions and prefers PFS. Background PFS is widely used as a surrogate endpoint in oncology. The definition of "progression" generally involves imaging techniques (plain radiograms, CT scans, MRI, PET scans, ultrasounds) or other aspects: biochemical progression may be defined on the basis of an increase in a tumor marker (such as CA125 for epithelial ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Breast Cancer
Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a red or scaly patch of skin. In those with distant spread of the disease, there may be bone pain, swollen lymph nodes, shortness of breath, or yellow skin. Risk factors for developing breast cancer include obesity, a lack of physical exercise, alcoholism, hormone replacement therapy during menopause, ionizing radiation, an early age at first menstruation, having children late in life or not at all, older age, having a prior history of breast cancer, and a family history of breast cancer. About 5–10% of cases are the result of a genetic predisposition inherited from a person's parents, including BRCA1 and BRCA2 among others. Breast cancer most commonly develops in cells from the lining of milk ducts and the lobules that supply these ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Melanoma
Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye (uveal melanoma). In women, they most commonly occur on the legs, while in men, they most commonly occur on the back. About 25% of melanomas develop from moles. Changes in a mole that can indicate melanoma include an increase in size, irregular edges, change in color, itchiness, or skin breakdown. The primary cause of melanoma is ultraviolet light (UV) exposure in those with low levels of the skin pigment melanin. The UV light may be from the sun or other sources, such as tanning devices. Those with many moles, a history of affected family members, and poor immune function are at greater risk. A number of rare genetic conditions, such as xeroderma pigmentosum, also increase the risk. Diagnosis is by biopsy and analysis of any skin lesion ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Phase II Clinical Trials
The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phases start with testing for safety in a few human subjects, then expand to many study participants (potentially tens of thousands) to determine if the treatment is effective. Clinical research is conducted on drug candidates, vaccine candidates, new medical devices, and new diagnostic assays. Summary Clinical trials testing potential medical products are commonly classified into four phases. The drug development process will normally proceed through all four phases over many years. If the drug successfully passes through Phases I, II, and III, it will usually be approved by the national regulatory authority for use in the general population. Phase IV trials are 'post-marketing' or 'surveillance' studies conducted to monitor safety over severa ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
