ENZYMES, GROWTH FACTORS, PROTEINS, AND RECEPTORS

Tyrosine Kinases

Enzymes that activate or phosphorylate pathways needed for proliferation, differentiation, evasion of apoptosis, and evasion of DNA repair mechanisms

EGFR (Epidermal growth factor receptor)

Receptor that growth factors found in the environment of the cell attach to, causing dimerization, phosphorylation, and activation of downstream signaling pathways

HER2

A receptor in the epidermal growth factor receptor (EGFR) family, targeted by pertuzumab and trastuzumab in HER2-positive breast cancers

PDGFR (Platelet-Derived Growth Factor Receptor)

Receptor targeted by imatinib, dasatinib, and nilotinib, important in pathways that lead to proliferation and evasion of apoptosis

SCF (Stem Cell Factor)

Targeted by imatinib, dasatinib, and nilotinib in the treatment of various myeloproliferative disorders and leukemias

KIT

Receptor targeted by imatinib, dasatinib, and nilotinib, associated with Ph-positive CML, Ph-positive ALL, and KIT-positive GIST

TIE2

Receptor targeted by ripretinib, an inhibitor used in the treatment of gastrointestinal stromal tumors

VEGFR2 (Vascular Endothelial Growth Factor Receptor 2)

Receptor targeted by ripretinib, used in the treatment of gastrointestinal stromal tumors

BRAF

Protein targeted by ripretinib (specifically wild-type), which is used for gastrointestinal stromal tumors

HER family

Receptor family targeted by tyrosine kinase inhibitors such as gefitinib, erlotinib, afatinib, and osimertinib, useful in the treatment of non-small cell lung cancers (NSCLC)

ALK (Anaplastic Lymphoma Kinase) receptors

Receptors targeted by tyrosine kinase inhibitors like crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib, used in ALK-positive non-small cell lung cancers and lymphomas

HGFR

Receptor targeted by tyrosine kinase inhibitors like crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib

ROS1

Receptor targeted by tyrosine kinase inhibitors like crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib, useful in ROS1-positive non-small cell lung cancers

c-Met

Receptor targeted by tyrosine kinase inhibitors such as crizotinib

RON

Receptor targeted by tyrosine kinase inhibitors such as crizotinib

MET receptor

Receptor targeted by tyrosine kinase inhibitors capmatinib and tepotinib, used in non-small cell lung cancers (NSCLC) that harbor mutations in this receptor

Wild-type RET

Protein targeted by pralsetinib and selpercatinib, useful in RET fusion-positive non-small cell lung cancers, RET mutant medullary thyroid cancer, and RET fusion-positive thyroid cancers

FGFR1, FGFR2, and FGFR3 (Fibroblast Growth Factor Receptor 1, 2, and 3)

Receptors targeted by pemigatinib and infigratinib, useful for the treatment of cholangiocarcinomas that harbor mutations in these receptors

FLT3 (FMS-like Tyrosine Kinase 3)

Receptor/pathway targeted by midostaurin and gilteritinib, found in patients who have acute myeloid leukemia (AML)

BRAF (Mutated forms)

Pathway targeted by vemurafenib and dabrafenib in the treatment of patients with melanoma

PI3K (Phosphatidylinositol 3-Kinase)

Pathway targeted by duvelisib and idelalisib, useful in the treatment of chronic lymphocytic leukemia

JAK1 and JAK2 (Janus Kinase 1 and 2)

Enzymes inhibited by ruxolitinib, which target the JAK/STAT proliferative pathway and are useful in myeloproliferative neoplasms

CDK4 and CDK6 (Cyclin-Dependent Kinase 4 and 6)

Enzymes targeted by ribociclib and palbociclib, associated with hormone receptor-positive HER2-negative breast cancer

BTK (Bruton's Tyrosine Kinases)

Enzymes targeted by zanubrutinib and ibrutinib, useful in the treatment of mantle cell lymphoma, Waldenstrom macroglobulinemia, and marginal zone lymphomas

PARP1, PARP2, and PARP3 (Poly (ADP-ribose) polymerase 1, 2, and 3)

Enzymes targeted by Olaparib, used in cancers with BRCA mutations such as ovarian, breast, pancreatic, and prostate cancer

DNMT (DNA methyltransferase)

Enzyme targeted by Azacitidine and Decitabine, useful in the treatment of myelodysplastic syndromes and acute myeloid leukemia

HDAC (histone deacetylase)

Enzyme targeted by Vorinostat, Belinostat, and Panobinostat, mutated in cases of cutaneous T-cell lymphomas and used in peripheral T-cell lymphomas and multiple myeloma

XPO1 (nuclear exporter 1)

Protein targeted by Selinexor, found in cases of multiple myeloma and diffuse large B-cell lymphoma

mTOR (mammalian target of rapamycin)

Pathway/protein inhibited by Temsirolimus and Everolimus, used in the treatment of renal cell carcinoma and hormone receptor-positive HER2-negative breast cancer

SMO

Target of Vismodegib, used for the treatment of locally advanced and metastatic pancreatic cancers

c-BRAF

Tyrosine kinase targeted by Sorafenib, used for hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), and refractory thyroid cancers

VEGFR1, VEGFR2, and VEGFR3 (Vascular Endothelial Growth Factor Receptor 1, 2, and 3)

Receptors targeted by Sorafenib, Sunitinib, Pazopanib, Axitinib, and others, important in angiogenesis pathways

PDGFR beta (Platelet-Derived Growth Factor Receptor beta)

Receptor targeted by Sorafenib, Sunitinib, Pazopanib, and others

AXL

Receptor targeted by Cabozantinib, used for RCC and HCC

TYRO3

Receptor targeted by Cabozantinib

MER

Receptor targeted by Cabozantinib

TRKB

Receptor targeted by Cabozantinib

FGFR1, FGFR2, FGFR3, and FGFR4 (Fibroblast Growth Factor Receptor 1, 2, 3, and 4)

Receptor family targeted by Lenvatinib

Androgen receptors

Activated by dihydrotestosterone (DHT) in prostate cancer, leading to cellular proliferation and evasion of apoptosis

Aromatase

Enzyme responsible for converting androstenedione to estrone, blocked by aromatase inhibitors to reduce estrogen synthesis in breast cancer

Estrogen receptors

Activated by estradiol, leading to transcription of genes promoting proliferation, apoptosis evasion, and survival advantage in breast cancer

5-Alpha Reductase

Enzyme inhibited by 5-alpha reductase inhibitors, preventing the conversion of testosterone to dihydrotestosterone (DHT)

LHRH (Luteinizing Hormone-Releasing Hormone)

Axis manipulated by LHRH agonists to inhibit signals from the hypothalamus, aiming to stop pituitary secretion of luteinizing hormone

Dihydrofolate reductase

Enzyme inhibited by Methotrexate, decreasing the synthesis of thymidylate, amino acids, and purine nucleotides

HGPRT (Hypoxanthine-guanine phosphoribosyltransferase)

Enzyme that activates 6-Mercaptopurine

Thymidylate synthase

Enzyme inhibited by 5-Fluorouracil, leading to a lack of thymine production and cell death

Ribonucleotide reductase

Enzyme inhibited by Cytarabine and Gemcitabine, reducing the formation of dNTPs

DNA topoisomerase II (DNA gyrase)

Enzyme inhibited by Etoposide, which normally removes supercoiling of DNA

DNA topoisomerase I

Enzyme inhibited by Topotecan and Irinotecan

Topoisomerase II

Enzyme inhibited by Doxorubicin, in addition to intercalating between base pairs

bcr-abl oncogene

Oncogene whose protein product's tyrosine kinase activity is inhibited by Imatinib in Chronic Myelogenous Leukemia (CML)

c-kit tyrosine kinase

Tyrosine kinase inhibited by Imatinib in Gastrointestinal Stromal Tumor (GIST)

HER2/neu receptor

Receptor for epidermal growth factor that is overexpressed in breast cancer cells and targeted by Trastuzumab

VEGF (Vascular Endothelial Growth Factor)

Growth factor whose binding to VEGFR is inhibited by Bevacizumab, inhibiting tumor vascular permeability

VEGFR (Vascular Endothelial Growth Factor Receptor)

Receptor for VEGF whose signaling is inhibited by Bevacizumab

CD20 surface protein

Protein in Non-Hodgkin's Lymphoma (NHL) cells that is bound and inhibited by Rituximab, inducing complement-mediated lysis, direct cytotoxicity, and apoptosis

Asparagine

Amino acid that is depleted by Asparaginase, an enzyme used to control cancer cell proliferation in Acute Lymphoblastic Leukemia (ALL)

Acrolein

Metabolite of Cyclophosphamide causing hemorrhagic cystitis by releasing inflammatory mediators

Heme carrier protein 1 (HCP1)

Protein through which heme-bound iron enters the enterocyte from the duodenal lumen

Duodenal cytochrome B (dcytb)

Enzyme that converts ingested free (nonheme) iron from its Fe3+ (ferric) form to its Fe2+ (ferrous) form for absorption

DMT1 (divalent metal transporter 1)

Cotransporter that brings Fe2+ (ferrous) iron and the H+ proton into the enterocyte

Ferritin

Storage form of mucosal iron in the enterocyte

Ferroportin

Protein through which Fe2+ (ferrous) iron exits the duodenal cell

Hephaestin

Enzyme that converts Fe2+ (ferrous) iron to its Fe3+ (ferric) iron form upon exit from the duodenal cell via ferroportin

Transferrin

Protein that transports Fe3+ (ferric) iron through the blood to wherever it is needed

Cobalamin (Vitamin B12)

Vitamin that scavenges the methyl group from N5-Methyltetrahydrofolate (MTHF), transforming it into Tetrahydrofolate in the folate cycle

Intrinsic factor (IF)

Transport and delivery binding protein produced by parietal cells in the stomach, needed for Vitamin B12 absorption in the terminal ileum

Erythroid receptors

Receptors on red cell progenitors that Epoetin (a recombinant product) interacts with to stimulate red cell mass increase

G-CSF (Granulocyte-colony stimulating factor)

Cytokine that stimulates proliferation and differentiation via receptors on myeloid cells, and activates phagocytic activity of mature neutrophils

GM-CSF (Granulocyte-macrophage colony stimulating factors)

Cytokine that stimulates proliferation and differentiation via receptors on myeloid cells

IL-11 (Interleukin 11)

Recombinant form of a thrombopoietic growth factor that enhances megakaryocyte maturation and increases peripheral blood platelet counts

Thrombopoietin

Growth factor that activates the Mpl receptors to produce more platelets

Mpl receptors

Receptors activated by Thrombopoietin and TPOR mimetics (e.g., Romiplostim, Eltrombopag, Avatrombopag) to stimulate megakaryopoiesis

Plasmepsin I/II and falcipain

Enzymes that metabolize hemoglobin into heme and globin in Plasmodium

PfATP6

ATPase in Plasmodium that ensures normal intracellular Ca2+ levels, and whose disruption leads to high intracellular Ca2+ and parasite death

Cysteine proteases

Enzymes responsible for hemoglobin digestion that are disabled by artemisinin-induced alkylation

Dihydrofolate reductase (DHFR) and Dihydropteroate synthase (DHPS)

Two enzymes needed for folic acid synthesis in Plasmodium that are targeted by synthesis inhibitors

Ubiquinone

Molecule that Atovaquone competes and counteracts with, leading to the collapse of the mitochondrial complex and inhibition of ATP synthesis in Plasmodium

80S ribosomes

Organelles whose function is blocked by Mefloquine, a proposed secondary mechanism of action, thereby inhibiting protein synthesis in Plasmodium

Apicoplast

Organelle whose formation is impaired by Doxycycline, which consequently impairs invasion of the Plasmodium parasite into the target cell

50S ribosome

Organelle blocked by Clindamycin, an antibiotic that blocks protein synthesis in Plasmodium