Lapatinib (INN), used in the form of lapatinib ditosylate (USAN) is an orally active drug for breast cancer and other solid tumours. It is a dual tyrosine kinase inhibitor which interrupts the HER2/neu and epidermal growth factor receptor (EGFR) pathways. It is used in combination therapy for HER2-positive breast cancer. It is used for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress HER2 (ErbB2).
Pertuzumab, sold under the brand name Perjeta, is a monoclonal antibody used in combination with trastuzumab and docetaxel for the treatment of metastatic HER2-positive breast cancer; it also used in the same combination as a neoadjuvant in early HER2-positive breast cancer.
The Cyclin D/Cdk4 complex is a multi-protein structure consisting of the proteins Cyclin D and cyclin-dependent kinase 4, or Cdk4, a serine-threonine kinase. This complex is one of many cyclin/cyclin-dependent kinase complexes that are the "hearts of the cell-cycle control system" and govern the cell cycle and its progression. As its name would suggest, the cyclin-dependent kinase is only active and able to phosphorylate its substrates when it is bound by the corresponding cyclin. The Cyclin D/Cdk4 complex is integral for the progression of the cell from the Growth 1 phase to the Synthesis phase of the cell cycle, for the Start or G1/S checkpoint.
Triple-negative breast cancer (TNBC) is any breast cancer that either lacks or shows low levels of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) overexpression and/or gene amplification. Triple-negative is sometimes used as a surrogate term for basal-like.
A CDK inhibitor is any chemical that inhibits the function of CDKs. They are used to treat cancers by preventing overproliferation of cancer cells. The US FDA approved the first drug of this type, palbociclib (Ibrance), a CDK4/6 inhibitor, in February 2015, for use in postmenopausal women with breast cancer that is estrogen receptor positive and HER2 negative. While there are multiple cyclin/CDK complexes regulating the cell cycle, CDK inhibitors targeting CDK4/6 have been the most successful; four CDK4/6 inhibitors have been FDA approved. No inhibitors targeting other CDKs have been FDA approved, but several compounds are in clinical trials.
Trastuzumab emtansine, sold under the brand 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.
Palbociclib, sold under the brand name Ibrance among others, is a medication developed by Pfizer for the treatment of HR-positive and HER2-negative breast cancer. It is a selective inhibitor of the cyclin-dependent kinases CDK4 and CDK6. Palbociclib was the first CDK4/6 inhibitor to be approved as a cancer therapy.
Sacituzumab govitecan, sold under the brand name Trodelvy by Gilead Sciences, is a Trop-2-directed antibody and topoisomerase inhibitor drug conjugate used for the treatment of metastatic triple-negative breast cancer and metastatic urothelial cancer.
Buparlisib is an experimental anti-cancer medication. It is a small molecule orally-available pan-class I phosphoinositide 3-kinase (PI3K) inhibitor. Buparlisib was under investigation as a treatment for advanced breast cancer but was abandoned due to negative results. It is still under investigation as a potential treatment for head and neck squamous cell carcinoma (HNSCC).
Abemaciclib, sold under the brand name Verzenio among others, is a medication for the treatment of advanced or metastatic breast cancers. It was developed by Eli Lilly and it acts as a CDK inhibitor selective for CDK4 and CDK6.
Ribociclib, sold under the brand name Kisqali, is a medication used for the treatment of certain kinds of breast cancer. Ribociclib is a kinase inhibitor. It was developed by Novartis and Astex Pharmaceuticals.
Alpelisib, sold under the brand name Piqray among others, is a medication used to treat certain types of breast cancer. It is used together with fulvestrant. It is taken by mouth. It is marketed by Novartis.
Elacestrant, sold under the brand name Orserdu, is an anticancer medication which is used in the treatment of breast cancer. It is taken by mouth.
Tucatinib, sold under the brand name Tukysa, is an anticancer medication used for the treatment of HER2-positive breast cancer. It is a small molecule inhibitor of HER2. It was developed by Array BioPharma and licensed to Cascadian Therapeutics.
Gedatolisib (PF-05212384) is an experimental drug for treatment of cancer in development by Celcuity, Inc. The mechanism of action is accomplished by binding the different p110 catalytic subunit isoforms of PI3K and the kinase site of mTOR.
Trastuzumab deruxtecan, sold under the brand name Enhertu, is an antibody-drug conjugate consisting of the humanized monoclonal antibody trastuzumab (Herceptin) covalently linked to the topoisomerase I inhibitor deruxtecan. It is licensed for the treatment of breast cancer or gastric or gastroesophageal adenocarcinoma. Trastuzumab binds to and blocks signaling through epidermal growth factor receptor 2 (HER2/neu) on cancers that rely on it for growth. Additionally, once bound to HER2 receptors, the antibody is internalized by the cell, carrying the bound deruxtecan along with it, where it interferes with the cell's ability to make DNA structural changes and replicate its DNA during cell division, leading to DNA damage when the cell attempts to replicate itself, destroying the cell.
G1 Therapeutics, Inc. is an American biopharmaceutical company headquartered in Research Triangle Park, North Carolina. The company specializes in developing and commercializing small molecule therapeutics for the treatment of patients with cancer.
Inavolisib, or GDC-0077, is an investigational, highly selective inhibitor and degrader of mutant phosphatidylinositol 3-kinase (PI3K) alpha. The PI3K-mediated signalling pathway has shown to play an important role in the development of tumours as dysregulation is commonly associated with tumour growth and resistance to antineoplastic agents and radiotherapy.
BPI-16350 is a small molecule CDK4/6 inhibitor that is being studied for the treatment of cancer. It has a similar structure to abemaciclib but is more selective for CDK4/6 over CDK9 according to preclinical research.
Capivasertib, sold under the brand name Truqap, is an anti-cancer medication used for the treatment of breast cancer. It is taken by mouth.
