Epigenetic pathway-BRD4

BRD4 is a member of the BET (bromodomain and extra terminal domain) family, containing two bromodomains that recognize acetylated lysine residues and an extended C-terminal domain with little sequence homology to other BET family members. BRD4 overexpression is observed in many cancer cells, and its inhibition is associated with the downregulation of c-Myc, following the apoptosis of the cells.

Receptor Tyrosine Kinase-ALK

The ALK (anaplastic lymphoma kinase) gene encodes a tyrosine kinase belonging to the insulin receptor superfamily. ALK is abundantly expressed in neural tissue during embryogenesis, but levels fall during early evelopment, so that in adults it is expressed only in rare scattered neural cells. ALK was originally identified in anaplastic large cell lymphoma (ALCL) cells as the product of a recurring chromosomal translocation, t (2;5; p23;q35), between the ALK gene on chromosome 2 and the nucleophosmin (NPM) gene on chromosome 5, which gives rise to expression of the NPM–ALK fusion protein.

Receptor Tyrosine Kinase-EGFR

GFR, also known as ERBB1 and HER1, is a transmembrane tyrosine kinase receptor (RTK). EGFR is a member of the human epidermal receptor (HER) family and a crucial component of cell signal pathways. Binding with ligands (EGF and TGF-α) leads to conformational changes in EGFR homo-dimerization or hetero-dimerization with other HER family members HER2, HER3 and ERBB4. Overexpression and activating mutations of EGFR, which have been reported in up to 30% of solid tumors (including breast, colorectal, lung, pancreatic, gastric, head and neck cancer, and glioblastomas.).

Endocrinology-ESR1

Human gene ESR1 (EStrogen Receptor 1) encodes a receptor Estrogen receptor alpha (ERα), also known as NR3A1 (nuclear receptor subfamily 3, group A, member 1), is one of two main types of estrogen receptor, a nuclear receptor that is activated by the sex hormone estrogen. ERα is a ligand-activated transcription factor composed of several domains important for hormone binding, DNA binding, and activation of transcription.

SNIPER

SNIPERs (Specific and Non-genetic Inhibitor of apoptosis protein [IAP]-dependent Protein ERaser), recognised as a kind of PROTACs, induce the degradation of both POIs and cIAP1, which may limit the full potential and duration of knockdown activity. However, cIAP1 is an antiapoptotic protein frequently overexpressed in human tumor cells, which is believed to be involved in resistance to tumor therapy. Therefore, degradation of cIAP1 simultaneously with POIs by SNIPERs could be beneficial to effectively kill cancer cells.