Chemotherapy is a type of cancer treatment that uses one or more anti-cancer drugs as part of a standardized chemotherapy regimen. Chemotherapy may be given with a curative intent, or it may aim to prolong life or to reduce symptoms. Chemotherapy is one of the major categories of the medical discipline specifically devoted to pharmacotherapy for cancer, which is called medical oncology.
Paclitaxel (PTX), sold under the brand name Taxol among others, is a chemotherapy medication used to treat a number of types of cancer. This includes ovarian cancer, breast cancer, lung cancer, Kaposi sarcoma, cervical cancer, and pancreatic cancer. It is given by injection into a vein. There is also an albumin-bound formulation.
Docetaxel, sold under the brand name Taxotere among others, is a chemotherapy medication used to treat a number of types of cancer. This includes breast cancer, head and neck cancer, stomach cancer, prostate cancer and non-small-cell lung cancer. It may be used by itself or along with other chemotherapy medication. It is given by slow injection into a vein.
Taxanes are a class of diterpenes. They were originally identified from plants of the genus Taxus (yews), and feature a taxadiene core. Paclitaxel (Taxol) and docetaxel (Taxotere) are widely used as chemotherapy agents. Cabazitaxel was FDA approved to treat hormone-refractory prostate cancer.
Paclitaxel total synthesis in organic chemistry is a major ongoing research effort in the total synthesis of paclitaxel (Taxol). This diterpenoid is an important drug in the treatment of cancer but, also expensive because the compound is harvested from a scarce resource, namely the Pacific yew. Not only is the synthetic reproduction of the compound itself of great commercial and scientific importance, but it also opens the way to paclitaxel derivatives not found in nature but with greater potential.
The epothilones are a class of potential cancer drugs. Like taxanes, they prevent cancer cells from dividing by interfering with tubulin, but in early trials epothilones have better efficacy and milder adverse effects than taxanes.
Breast cancer chemotherapy refers to the use of cytotoxic drugs (chemotherapy) in the treatment of breast cancer.
A mitotic inhibitor is a drug that inhibits mitosis, or cell division. These drugs disrupt microtubules, which are structures that pull the chromosomes apart when a cell divides. Mitotic inhibitors are used in cancer treatment, because cancer cells are able to grow and eventually spread through the body (metastasize) through continuous mitotic division. Thus, cancer cells are more sensitive to inhibition of mitosis than normal cells. Mitotic inhibitors are also used in cytogenetics, where they stop cell division at a stage where chromosomes can be easily examined.
Class III β-tubulin, otherwise known as βIII-tubulin (β3-tubulin) or β-tubulin III, is a microtubule element of the tubulin family found almost exclusively in neurons, and in testis cells. In humans, it is encoded by the TUBB3 gene.
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.
Tesetaxel is an orally administered taxane being investigated as a chemotherapy agent for various types of cancer, including breast cancer, gastric cancer, colorectal cancer, and other solid tumors. It differs from other members of the taxane class in that it is administered orally, not intravenously.
Paclitaxel trevatide is an experimental chemotherapy drug that is under development by Angiochem Inc, a Canadian biotech company. Phase II clinical trials have completed for several indications, and the company is preparing for phase III trials.
Metastatic breast cancer, also referred to as metastases, advanced breast cancer, secondary tumors, secondaries or stage IV breast cancer, is a stage of breast cancer where the breast cancer cells have spread to distant sites beyond the axillary lymph nodes. There is no cure for metastatic breast cancer; it often can be effectively treated. There is no stage after IV.
Genta Incorporated was a biopharmaceutical company started in La Jolla, California, which discovered and developed innovative drugs for the treatment of patients with cancer. Founded in 1989 by a highly skilled entrepreneur, the company focused on a novel technology known as antisense, which targets gene products that are associated with the onset and progression of serious diseases. At that time, only Ionis Pharmaceuticals, Inc. was conducting significant research with this technology. Antisense is a short span of oligonucleotides – modified DNA structures ranging from about 12-24 bases that selectively bind to specific RNA. The intent is to block expression of an aberrant protein that contributes to the disease of interest. Genta in-licensed three different antisense molecules that blocked Bcl-2, a fibroblast growth factor (FGF), and the gene c-myb, respectively.
Cabazitaxel is a semi-synthetic derivative of a natural taxoid. It was developed by Sanofi-Aventis and was approved by the U.S. FDA for the treatment of hormone-refractory prostate cancer on June 17, 2010. It is a microtubule inhibitor, and the fourth taxane to be approved as a cancer therapy.
Trastuzumab emtansine also known as ado-trastuzumab emtansine and sold under the trade name Kadcyla, is an antibody-drug conjugate consisting of the humanized monoclonal antibody trastuzumab (Herceptin) covalently linked to the cytotoxic agent DM1. Trastuzumab alone stops growth of cancer cells by binding to the HER2 receptor, whereas trastuzumab emtansine undergoes receptor-mediated internalization into cells, is catabolized in lysosomes where DM1-containing catabolites are released and subsequently bind tubulin to cause mitotic arrest and cell death. Trastuzumab binding to HER2 prevents homodimerization or heterodimerization (HER2/HER3) of the receptor, ultimately inhibiting the activation of MAPK and PI3K/AKT cellular signalling pathways. Because the monoclonal antibody targets HER2, and HER2 is only over-expressed in cancer cells, the conjugate delivers the cytotoxic agent DM1 specifically to tumor cells. The conjugate is abbreviated T-DM1.
Tubulin inhibitors are chemotherapy drugs that interfere directly with the tubulin system, which is in contrast to those chemotherapy drugs acting on DNA. Microtubules play an important role in eukaryotic cells. Alpha- and beta-tubulin, the main components of microtubules, have gained considerable interest because of their function and biophysical properties and has become the subject of intense study. The addition of tubulin ligands can affect microtubule stability and function, including mitosis, cell motion and intracellular organelle transport. Tubulin binding molecules have generated significant interest after the introduction of the taxanes into clinical oncology and the general use of the vinca alkaloids. These compounds inhibit cell mitosis by binding to the protein tubulin in the mitotic spindle and preventing polymerization or depolymerization into the microtubules. This mode of action is also shared with another natural agent called colchicine.
Taccalonolides are a class of microtubule-stabilizing agents isolated from Tacca chantrieri that has been shown to have selective cancer-fighting properties. Other examples of microtubule-stabilizing agents include taxanes and epothilones, both of which prevent cancer cells from dividing by interfering with tubulin. While taxanes like Paclitaxel and docetaxel have been used successfully against breast, ovarian, prostate, and non–small-cell lung cancers, intrinsic and acquired drug resistance limit their anticancer properties. Unlike taxanes, taccalonolides appear to work through a different mechanism of action that does not involve tubulin, although recently isolated taccalonolides AF and AJ have shown tubulin-interaction activity. The discovery of taccalonolides opens up new possibilities to treat cancer cells, especially ones that are taxane or epithilone resistant.
Iwao Ojima is a Japanese-American chemist and University Distinguished Professor at the State University of New York at Stony Brook. He has been widely recognized for his seminal contributions to a range of chemical research at the multifaceted interfaces of chemical synthesis and life sciences. As rare accomplishments, he has received four National Awards from the American Chemical Society in four different fields of research. He is also serving as the Director of the Institute of Chemical Biology and Drug Discovery (ICB&DD), as well as the President of the Stony Brook Chapter of the National Academy of Inventors.
2-Methoxyestradiol disulfamate, or 2-methoxyestradiol 3,17β-O,O-bis(sulfamate), is a synthetic, oral active anti-cancer medication which was previously under development for potential clinical use. It has improved potency, low metabolism, and good pharmacokinetic properties relative to 2-methoxyestradiol (2-MeO-E2). It is also a potent inhibitor of steroid sulfatase, the enzyme that catalyzes the desulfation of steroids such as estrone sulfate and dehydroepiandrosterone sulfate (DHEA-S).
