Targeted therapy or molecularly targeted therapy is one of the major modalities of medical treatment (pharmacotherapy) for cancer, others being hormonal therapy and cytotoxic chemotherapy. As a form of molecular medicine, targeted therapy blocks the growth of cancer cells by interfering with specific targeted molecules needed for carcinogenesis and tumor growth, rather than by simply interfering with all rapidly dividing cells. Because most agents for targeted therapy are biopharmaceuticals, the term biologic therapy is sometimes synonymous with targeted therapy when used in the context of cancer therapy. However, the modalities can be combined; antibody-drug conjugates combine biologic and cytotoxic mechanisms into one targeted therapy.
Tipifarnib is a farnesyltransferase inhibitor. Farnesyltransferase inhibitors block the activity of the farnesyltransferase enzyme by inhibiting prenylation of the CAAX tail motif, which ultimately prevents Ras from binding to the membrane, rendering it inactive.
Minretumomab (CC49) is a mouse monoclonal antibody that was designed for the treatment of cancers that express the TAG-72 antigen. This includes breast, colon, lung, and pancreatic cancers. Apparently, it never got past Phase I clinical trials for this purpose.
Cixutumumab (IMC-A12) is a human monoclonal antibody for the treatment of solid tumors.
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.
Glembatumumab vedotin is an antibody-drug conjugate (ADC) that targets cancer cells expressing transmembrane glycoprotein NMB (GPNMB).
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.
Vorsetuzumab mafodotin (SGN-75) is an antibody-drug conjugate (ADC) directed to the protein CD70 designed for the treatment of cancer. It is a humanized monoclonal antibody, vorsetuzumab, conjugated with noncleavable monomethyl auristatin F (MMAF), a cytotoxic agent.
Duligotuzumab (INN) is a humanized IgG1 monoclonal antibody designed for the treatment of cancer. It acts as an immunomodulator and binds to HER3. It is in development by Roche. Clinical development for head and neck cancer and colorectal cancer have been discontinued, but phase I trials in combination with cobimetinib are evaluating safety for treatment of solid tumors.
Seagen Inc. is an American biotechnology company focused on developing and commercializing innovative, empowered monoclonal antibody-based therapies for the treatment of cancer. The company, headquartered in Bothell, Washington, is the industry leader in antibody-drug conjugates or ADCs, a technology designed to harness the targeting ability of monoclonal antibodies to deliver cell-killing agents directly to cancer cells. Antibody-drug conjugates are intended to spare non-targeted cells and thus reduce many of the toxic effects of traditional chemotherapy, while potentially enhancing antitumor activity.
Varlilumab is a monoclonal antibody designed for immunotherapy for solid tumors and hematologic malignancies. It is an anti-CD27 antibody and helps activate T-cells.
Enfortumab vedotin, sold under the brand name Padcev, is an antibody-drug conjugate used for the treatment of urothelial cancer. It is a nectin-4-directed antibody and microtubule inhibitor conjugate. Enfortumab refers to the monoclonal antibody part, and vedotin refers to the payload drug (MMAE) and the linker.
Sacituzumab govitecan, sold under the brand name Trodelvy, 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.
Indusatumab vedotin (MLN-0264) is an antibody-drug conjugate that is under development for the treatment of pancreatic cancer and other gastrointestinal cancers. It consists of a monoclonal antibody (indusatumab) that targets the enzyme guanylate cyclase 2C which is present in some cancers, linked to an average of three to four molecules of the chemotherapeutic agent monomethyl auristatin E (MMAE).
Denintuzumab mafodotin is a humanized monoclonal antibody-drug conjugate designed for the treatment of CD19-positive acute lymphoblastic leukemia and B-cell non-Hodgkin lymphoma. It consists of an anti-CD19 mAb linked to monomethyl auristatin F (MMAF), a cytotoxic agent. This drug was developed by Seattle Genetics.
Rovalpituzumab tesirine (Rova-T) is an experimental antibody-drug conjugate targeting the protein DLL3 on tumor cells. It was originally developed by Stemcentrx and was purchased by AbbVie. It was tested for use in small-cell lung cancer, but development was terminated after unsuccessful phase III trial.
Cofetuzumab pelidotin is an experimental antibody-drug conjugate in development for the treatment of cancer. It was created by Stemcentrx and is being developed by Pfizer. The drug is an anti-PTK7 monoclonal antibody linked to auristatin-0101, an auristatin microtubule inhibitor.
Dostarlimab, sold under the brand name Jemperli, is a monoclonal antibody used as a medication for the treatment of endometrial cancer. Dostarlimab is a programmed death receptor-1 (PD-1)–blocking monoclonal antibody.
Belantamab mafodotin, sold under the brand name Blenrep, is a medication for the treatment of relapsed and refractory multiple myeloma.
Tisotumab vedotin, sold under the brand name Tivdak, is an antibody-drug conjugate used to treat cervical cancer. It is a combination of tisotumab, a monoclonal antibody against tissue factor, and monomethyl auristatin E (MMAE), a potent inhibitor of cell division. It is administered by infusion into a vein.
