Biological Pathway Reviews
ALK is a tyrosine kinase receptor that resides on chromosome 2p23.
Chromosomal rearrangements resulting in fusion genes leads to ALK tyrosine kinase that promote cell survival by activating a signaling pathway or by inhibition of apoptosis, which leads to cell proliferation.1
Read More »Tumor cells have many characteristics, including genomic instability and oncogene activation, which should lead to apoptosis.1 In a bid to survive, tumor cells may become dependent on the BCL-2 protein.2 Certain cancer cells will overexpress BCL-2, which in turn impedes apoptosis and facilitates tumor growth and resistance to chemotherapy.3 These malignant cells that depend on BCL-2 for survival are likely to be sensitive to BCL-2 modulation.4
Read More »BCMA is a member of the tumor necrosis factor receptor family that is expressed on plasma cells and on late stage normal and malignant B-cells.1 BCMA binds to BAFF, activating the NF-kB and MAPK8/JNK signaling pathways, which leads to the proliferation and survival of plasma cells.2
BCMA can also bind to a proliferation-inducing ligand (APRIL), which is associated with B cell development. Both ligands are associated with the regulation of cell survival and growth.3
Read More »Oncogenic mutations in BRAF genes activate the RAF/MEK/ERK pathway, resulting in increased cell proliferation and resistance to apoptosis.1 BRAF mutations have been identified in 7% to 8% of all cancers.2 V600E is the most common activating mutations in BRAF and is associated with more aggressive cancer and worse prognosis.1,3
Read More »Bruton's tyrosine kinase (BTK), a non-receptor tyrosine kinase, plays an important role in B-cell receptor activation.1 BCR activation results in translocation and phosphorylation of BTK. When BTK is inducted it activates phospholipase C and calcium mobilization, which results in downstream events, including proliferation, maturation, differentiation, and survival.2
Read More »CD19 antigen is a type I transmembrane glycoprotein that is expressed in normal and malignant B cells.1 It plays a role in B cell development and maturation by modulating B-cell receptor signaling during lymphopoiesis.2,3 CD-19 deficiency leads to an impaired humoral response, resulting in increased susceptibility to infection.1,3
Read More »CD30, a member of the tumor necrosis factor receptor superfamily, is expressed on active B cells and T cells.1 Signal mediation by CD30 through TRAF2 and TRAF5 can activate the transcription factor NF-κB pathway, leading to a positive regulation of the apoptotic process.2 CD30 can also signal the MAPK pathways, resulting in the survival of neoplastic cells. A positive feedback loop between the MAPK pathway and a nuclear transcription factor plays a role in the upregulation of CD30.2
Read More »The growth-factor-receptor tyrosine kinase family includes EGFR (ErbB1, HER1), ErbB2 (HER2, neu in rodents), ErbB3 (HER3), and ErbB4 (HER4).1 Receptor overexpression and ligand-dependent and ligand-independent mechanisms can cause abnormal EGFR activation. When EGFR is overexpressed in contributes to tumorigenesis, driving aggressive cell growth.2 It is recognized as a biomarker of resistance in tumors.3
Read More »By modulating critical gene expression, EZH2 promotes cell cycle progression, cell proliferation, differentiation, and apoptosis.1 EZH2 is overexpressed in several malignant tumors and recurrently mutated in other cancers.2 It provides a critical role in promoting tumor growth and metastasis and can be regulated through multiple pathways transcriptionally, post-transcriptionally, and post-translationally.2
Read More »Programmed death-ligand 1 (PD-L1) is a 40kDa type 1 transmembrane protein that plays a key role in keeping the body’s immune responses in check, especially during cases of autoimmune disease and viral infection.1 PD-L1 can be found on certain normal cells and in excessive amounts on some cancer cells. When PD-L1 binds to PD-1, a protein found on T-cells, it inhibits the T-cells from activating and killing cells comprising PD-L1, including cancer cells.2 Immune checkpoint inhibitors bind to PD-L1 and keep it from binding to PD-1, thus releasing PD-L1’s hold on the immune system and allowing T-cells to freely kill cancer cells.
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