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Other names | Combretastatin A-4 phosphate; CA4P; CA4PD; fosbretabulin disodium; fosbretabulin tromethamine |
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Formula | C18H21O8P |
Molar mass | 396.332 g·mol−1 |
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Fosbretabulin (also known as combretastatin A-4 phosphate or CA4P) is a microtubule destabilizing experimental drug, a type of vascular-targeting agent, a drug designed to damage the vasculature (blood vessels) of cancer tumours causing central necrosis. It is a derivative of combretastatin. It is formulated as the salts fosbretabulin disodium and fosbretabulin tromethamine. [1]
Fosbretabulin is a prodrug. In vivo , it is dephosphorylated to its active metabolite, combretastatin A-4. [2]
In July 2007, the pharmaceutical company OXiGENE initiated a 180-patient phase III clinical trial of fosbretabulin in combination with carboplatin for the treatment of anaplastic thyroid cancer. [3] There is currently no fully FDA approved treatment for this form of cancer. By 2017, it had completed multiple clinical trials (e.g. for solid tumours, [4] non-small cell lung cancer [5] ) with more in progress. [6]
Bevacizumab, sold under the brand name Avastin among others, is a medication used to treat a number of types of cancers and a specific eye disease. For cancer, it is given by slow injection into a vein (intravenous) and used for colon cancer, lung cancer, glioblastoma, and renal-cell carcinoma. In many of these diseases it is used as a first-line therapy. For age-related macular degeneration it is given by injection into the eye (intravitreal).
Anaplastic thyroid cancer (ATC), also known as anaplastic thyroid carcinoma, is an aggressive form of thyroid cancer characterized by uncontrolled growth of cells in the thyroid gland. This form of cancer generally carries a very poor prognosis due to its aggressive behavior and resistance to cancer treatments. The cells of anaplastic thyroid cancer are highly abnormal and usually no longer resemble the original thyroid cells and have poor differentiation.
Cixutumumab (IMC-A12) is a human monoclonal antibody for the treatment of solid tumors.
Ramucirumab is a fully human monoclonal antibody (IgG1) developed for the treatment of solid tumors. This drug was developed by ImClone Systems Inc. It was isolated from a native phage display library from Dyax.
Tigatuzumab (CS-1008) is a monoclonal antibody for the treatment of cancer. As of October 2009, a clinical trial for the treatment of pancreatic cancer, Phase II trials for colorectal cancer, non-small cell lung cancer, and ovarian cancer have been completed.
Veliparib (ABT-888) is a potential anti-cancer drug acting as a PARP inhibitor. It kills cancer cells by blocking a protein called PARP, thereby preventing the repair of DNA or genetic damage in cancer cells and possibly making them more susceptible to anticancer treatments. Veliparib may make whole brain radiation treatment work more effectively against brain metastases from NSCLC. It has been shown to potentiate the effects of many chemotherapeutics, and as such has been part of many combination clinical trials.
Phosphoinositide 3-kinase inhibitors are a class of medical drugs that are mainly used to treat advanced cancers. They function by inhibiting one or more of the phosphoinositide 3-kinase (PI3K) enzymes, which are part of the PI3K/AKT/mTOR pathway. This signal pathway regulates cellular functions such as growth and survival. It is strictly regulated in healthy cells, but is always active in many cancer cells, allowing the cancer cells to better survive and multiply. PI3K inhibitors block the PI3K/AKT/mTOR pathway and thus slow down cancer growth. They are examples of a targeted therapy. While PI3K inhibitors are an effective treatment, they can have very severe side effects and are therefore only used if other treatments have failed or are not suitable.
Treatment of lung cancer refers to the use of medical therapies, such as surgery, radiation, chemotherapy, immunotherapy, percutaneous ablation, and palliative care, alone or in combination, in an attempt to cure or lessen the adverse impact of malignant neoplasms originating in lung tissue.
Crizotinib, sold under the brand name Xalkori among others, is an anti-cancer medication used for the treatment of non-small cell lung carcinoma (NSCLC). It acts as an ALK and ROS1 inhibitor.
ALK inhibitors are anti-cancer drugs that act on tumours with variations of anaplastic lymphoma kinase (ALK) such as an EML4-ALK translocation. They fall under the category of tyrosine kinase inhibitors, which work by inhibiting proteins involved in the abnormal growth of tumour cells. All the current approved ALK inhibitors function by binding to the ATP pocket of the abnormal ALK protein, blocking its access to energy and deactivating it. A majority of ALK-rearranged NSCLC harbour the EML4-ALK fusion, although as of 2020, over 92 fusion partners have been discovered in ALK+ NSCLC. For each fusion partner, there can be several fusion variants depending on the position the two genes were fused at, and this may have implications on the response of the tumour and prognosis of the patient.
Motesanib is an experimental drug candidate originally developed by Amgen but later investigated by the Takeda Pharmaceutical Company. It is an orally administered small molecule belonging to angiokinase inhibitor class which acts as an antagonist of VEGF receptors, platelet-derived growth factor receptors, and stem cell factor receptors. It is used as the phosphate salt motesanib diphosphate. After clinical trials in thyroid cancer, non-small cell lung cancer, gastrointestinal stromal cancer, colorectal cancer, and breast cancer, the drug was not found to show sufficient efficacy for further development, and development was abandoned by Takeda.
Nintedanib, sold under the brand names Ofev and Vargatef, is an oral medication used for the treatment of idiopathic pulmonary fibrosis and along with other medications for some types of non-small-cell lung cancer.
Angiokinase inhibitors are a new therapeutic target for the management of cancer. They inhibit tumour angiogenesis, one of the key processes leading to invasion and metastasis of solid tumours, by targeting receptor tyrosine kinases. Examples include nintedanib, afatinib and motesanib.
Nivolumab, sold under the brand name Opdivo, is a medication used to treat a number of types of cancer. This includes melanoma, lung cancer, malignant pleural mesothelioma, renal cell carcinoma, Hodgkin lymphoma, head and neck cancer, urothelial carcinoma, colon cancer, esophageal squamous cell carcinoma, liver cancer, gastric cancer, and esophageal or gastroesophageal junction (GEJ) cancer. It is used by slow injection into a vein.
Demcizumab is a humanized monoclonal antibody which is used to treat patients with pancreatic cancer or non-small cell lung cancer. Demcizumab has completed phase 1 trials and is currently undergoing phase 2 trials. Demcizumab was developed by OncoMed Pharmaceuticals in collaboration with Celgene.
Aldoxorubicin (INNO-206) is a tumor-targeted doxorubicin conjugate in development by CytRx. Specifically, it is the (6-maleimidocaproyl) hydrazone of doxorubicin. Essentially, this chemical name describes doxorubicin attached to an acid-sensitive linker.
Atezolizumab, sold under the brand name Tecentriq, is a monoclonal antibody medication used to treat urothelial carcinoma, non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), small cell lung cancer (SCLC), hepatocellular carcinoma, and alveolar soft part sarcoma. It is a fully humanized, engineered monoclonal antibody of IgG1 isotype against the protein programmed cell death-ligand 1 (PD-L1).
Triciribine is a cancer drug which was first synthesized in the 1970s and studied clinically in the 1980s and 1990s without success. Following the discovery in the early 2000s that the drug would be effective against tumours with hyperactivated Akt, it is now again under consideration in a variety of cancers. As PTX-200, the drug is currently in two early stage clinical trials in breast cancer and ovarian cancer being conducted by the small molecule drug development company Prescient Therapeutics.
Dostarlimab, sold under the brand name Jemperli, is a monoclonal antibody used as an anti-cancer medication for the treatment of endometrial cancer. Dostarlimab is a programmed death receptor-1 (PD-1)–blocking monoclonal antibody.
Roy S. Herbst is an American oncologist who is the Ensign Professor of Medicine, Professor of Pharmacology, Chief of Medical Oncology, and Associate Director for Translational Research at Yale Cancer Center and Yale School of Medicine in New Haven, Connecticut.