Spiradenoma

Target: binding of epidermal growth factor (EGF) and other ligands to epidermal growth factor receptor (EGFR, HER1, c-ErbB-1)
Action: inhibitor
FDA: The epidermal growth factor receptor (EGFR, HER1, c-ErbB-1) is a transmembraneglycoprotein that is a member of a subfamily of type I receptor tyrosine kinases including EGFR,HER2, HER3, and HER4. The EGFR is constitutively expressed in many normal epithelialtissues, including the skin and hair follicle. Expression of EGFR is also detected in many humancancers including those of the head and neck, colon, and rectum. Cetuximab binds specifically to the EGFR on both normal and tumor cells, and competitivelyinhibits the binding of epidermal growth factor (EGF) and other ligands, such as transforminggrowth factor-alpha. In vitro assays and in vivo animal studies have shown that binding ofcetuximab to the EGFR blocks phosphorylation and activation of receptor-associated kinases,resulting in inhibition of cell growth, induction of apoptosis, and decreased matrixmetalloproteinase and vascular endothelial growth factor production. Signal transduction throughthe EGFR results in activation of wild-type Ras proteins, but in cells with activating Ras somaticmutations, the resulting mutant Ras proteins are continuously active regardless of EGFRregulation.In vitro, cetuximab can mediate antibody-dependent cellular cytotoxicity (ADCC) against certainhuman tumor types. In vitro assays and in vivo animal studies have shown that cetuximabinhibits the growth and survival of tumor cells that express the EGFR. No anti-tumor effects ofcetuximab were observed in human tumor xenografts lacking EGFR expression. The addition ofcetuximab to radiation therapy or irinotecan in human tumor xenograft models in mice resultedin an increase in anti-tumor effects compared to radiation therapy or chemotherapy alone.

Target: estrogenic pathways
Action: can be an activator or antooagonist
FDA: Decreases in estrogen levels after oophorectomy or menopause lead to increases in bone resorption andaccelerated bone loss. Bone is initially lost rapidly because the compensatory increase in bone formation isinadequate to offset resorptive losses. In addition to loss of estrogen, this imbalance between resorption andformation may be due to age-related impairment of osteoblasts or their precursors. In some women, these changeswill eventually lead to decreased bone mass, osteoporosis, and increased risk for fractures, particularly of the spine,hip, and wrist. Vertebral fractures are the most common type of osteoporotic fracture in postmenopausal women.The biological actions of raloxifene are largely mediated through binding to estrogen receptors. This bindingresults in activation of certain estrogenic pathways and blockade of others. Thus, raloxifene is an estrogenagonist/antagonist, commonly referred to as a selective estrogen receptor modulator (SERM).Raloxifene decreases resorption of bone and reduces biochemical markers of bone turnover to thepremenopausal range. These effects on bone are manifested as reductions in the serum and urine levels of boneturnover markers, decreases in bone resorption based on radiocalcium kinetics studies, increases in bone mineraldensity (BMD), and decreases in incidence of fractures.

Target: histone deacetylase (HDAC)
Action: inhibitor
FDA: Romidepsin is a histone deacetylase (HDAC) inhibitor. HDACs catalyze the removal of acetyl groups from acetylated lysine residues in histones, resulting in themodulation of gene expression. HDACs also deacetylate non-histone proteins, such as transcription factors. In vitro, romidepsin causes the accumulation of acetylatedhistones, and induces cell cycle arrest and apoptosis of some cancer cell lines with IC50 values in the nanomolar range. The mechanism of the antineoplastic effect ofromidepsin observed in nonclinical and clinical studies has not been fully characterized.

Target: -
Action: -
FDA: Bendamustine is a bifunctional mechlorethamine derivative containing a purine-like benzimidazole ring.Mechlorethamine and its derivatives form electrophilic alkyl groups. These groups form covalent bonds with electronrichnucleophilic moieties, resulting in interstrand DNA crosslinks. The bifunctional covalent linkage can lead to celldeath via several pathways. Bendamustine is active against both quiescent and dividing cells. The exact mechanism ofaction of bendamustine remains unknown.