A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to the tyrosine residues of specific proteins inside a cell. It functions as an "on" or "off" switch in many cellular functions.
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors,which do not spread. Possible signs and symptoms include a lump,abnormal bleeding,prolonged cough,unexplained weight loss,and a change in bowel movements. While these symptoms may indicate cancer,they can also have other causes. Over 100 types of cancers affect humans.
Li–Fraumeni syndrome is a rare,autosomal dominant,hereditary disorder that predisposes carriers to cancer development. It was named after two American physicians,Frederick Pei Li and Joseph F. Fraumeni,Jr.,who first recognized the syndrome after reviewing the medical records and death certificates of 648 childhood rhabdomyosarcoma patients. This syndrome is also known as the sarcoma,breast,leukaemia and adrenal gland (SBLA) syndrome.
A mitogen is a small bioactive protein or peptide that induces a cell to begin cell division,or enhances the rate of division (mitosis). Mitogenesis is the induction (triggering) of mitosis,typically via a mitogen. The mechanism of action of a mitogen is that it triggers signal transduction pathways involving mitogen-activated protein kinase (MAPK),leading to mitosis.
Alfred George Knudson,Jr. was an American physician and geneticist specializing in cancer genetics. Among his many contributions to the field was the formulation of the Knudson hypothesis in 1971,which explains the effects of mutation on carcinogenesis.
ATM serine/threonine kinase or Ataxia-telangiectasia mutated,symbol ATM,is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks. It phosphorylates several key proteins that initiate activation of the DNA damage checkpoint,leading to cell cycle arrest,DNA repair or apoptosis. Several of these targets,including p53,CHK2,BRCA1,NBS1 and H2AX are tumor suppressors.
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.
Phosphatase and tensin homolog (PTEN) is a phosphatase in humans and is encoded by the PTEN gene. Mutations of this gene are a step in the development of many cancers,specifically glioblastoma,lung cancer,breast cancer,and prostate cancer. Genes corresponding to PTEN (orthologs) have been identified in most mammals for which complete genome data are available.
p16,is a protein that slows cell division by slowing the progression of the cell cycle from the G1 phase to the S phase,thereby acting as a tumor suppressor. It is encoded by the CDKN2A gene. A deletion in this gene can result in insufficient or non-functional p16,accelerating the cell cycle and resulting in many types of cancer.
Cyclin-dependent kinase inhibitor 1B (p27Kip1) is an enzyme inhibitor that in humans is encoded by the CDKN1B gene. It encodes a protein which belongs to the Cip/Kip family of cyclin dependent kinase (Cdk) inhibitor proteins. The encoded protein binds to and prevents the activation of cyclin E-CDK2 or cyclin D-CDK4 complexes,and thus controls the cell cycle progression at G1. It is often referred to as a cell cycle inhibitor protein because its major function is to stop or slow down the cell division cycle.
Breast cancer anti-estrogen resistance protein 1 is a protein that in humans is encoded by the BCAR1 gene.
Cyclin-dependent kinase 4 inhibitor B also known as multiple tumor suppressor 2 (MTS-2) or p15INK4b is a protein that is encoded by the CDKN2B gene in humans.
Neural precursor cell expressed developmentally down-regulated protein 9 (NEDD-9) is a protein that in humans is encoded by the NEDD9 gene. NEDD-9 is also known as enhancer of filamentation 1 (EF1),CRK-associated substrate-related protein (CAS-L),and Cas scaffolding protein family member 2 (CASS2). An important paralog of this gene is BCAR1.
CDKN2A, also known as cyclin-dependent kinase inhibitor 2A, is a gene which in humans is located at chromosome 9,band p21.3. It is ubiquitously expressed in many tissues and cell types. The gene codes for two proteins,including the INK4 family member p16 and p14arf. Both act as tumor suppressors by regulating the cell cycle. p16 inhibits cyclin dependent kinases 4 and 6 and thereby activates the retinoblastoma (Rb) family of proteins,which block traversal from G1 to S-phase. p14ARF activates the p53 tumor suppressor. Somatic mutations of CDKN2A are common in the majority of human cancers,with estimates that CDKN2A is the second most commonly inactivated gene in cancer after p53. Germline mutations of CDKN2A are associated with familial melanoma,glioblastoma and pancreatic cancer. The CDKN2A gene also contains one of 27 SNPs associated with increased risk of coronary artery disease.
Afatinib,sold under the brand name Gilotrif among others,is a medication used to treat non-small cell lung carcinoma (NSCLC). It belongs to the tyrosine kinase inhibitor family of medications. It is taken by mouth.
PARP inhibitors are a group of pharmacological inhibitors of the enzyme poly ADP ribose polymerase (PARP).
Adenocarcinoma of the lung is the most common type of lung cancer,and like other forms of lung cancer,it is characterized by distinct cellular and molecular features. It is classified as one of several non-small cell lung cancers (NSCLC),to distinguish it from small cell lung cancer which has a different behavior and prognosis. Lung adenocarcinoma is further classified into several subtypes and variants. The signs and symptoms of this specific type of lung cancer are similar to other forms of lung cancer,and patients most commonly complain of persistent cough and shortness of breath.
Squamous-cell carcinoma (SCC) of the lung is a histologic type of non-small-cell lung carcinoma (NSCLC). It is the second most prevalent type of lung cancer after lung adenocarcinoma and it originates in the bronchi. Its tumor cells are characterized by a squamous appearance,similar to the one observed in epidermal cells. Squamous-cell carcinoma of the lung is strongly associated with tobacco smoking,more than any other forms of NSCLC.
Maureen E. Murphy,Ph.D.,is a researcher at The Wistar Institute in Philadelphia. Her research focuses on the tumor suppressor genes p53 and p14arf.
Edna "Eti" Cukierman is a Mexican biochemist who is a professor at the Fox Chase Cancer Center. She serves as co-director of the Marvin &Concetta Greenberg Pancreatic Cancer Institute. Her research investigates pancreatic cancer and the tumor microenvironment.
