Cancer Cell Biology, Angiogenesis, and Leukemia Flashcards

Flashcards covering the hallmarks of cancer, the mechanisms and regulation of angiogenesis, the metastatic cascade, and the classification/characteristics of leukemias, lymphomas, and multiple myeloma.

Angiogenesis

The creation of new blood vessels, also known as "neovascularization," which is required for the growth of normal and neoplastic tissue.

J. Folkman (1995) Observation

The finding that in the absence of vessel formation, tumors grow only to a size limited by nutrient diffusion; after angiogenesis, tumor growth accelerates from linear to exponential.

Hallmarks of Cancer

The six core capabilities of cancer which include: sustaining proliferative signaling, evading growth suppressors, activating invasion and metastasis, enabling replicative immortality, inducing angiogenesis, and resisting cell death.

First Step of Vessel Formation

Initiation

Tumor Vasculature Characteristics

Vessels are often dilated, highly permeable ("leaky"), have more endothelial cells than normal, and follow irregular, chaotic organization such as AV shunts.

Endothelial Cell (EC) Mitogens

Growth factors that stimulate angiogenesis, including VEGF (vascular endothelial GF), acidic FGF (fibroblast growth factor), and basic FGF.

PD-ECGF

Platelet derived endothelial cell GF, which induces DNA synthesis in endothelial cells.

Angiotropin

A substance that acts as a chemotaxin for endothelial cells during angiogenesis.

Interferon alfa-2a

An angiogenesis inhibitor that suppresses the formation of bFGF by tumor cells.

TIMPs

Tissue Inhibitors of Metalloproteinases, which function as collagenase inhibitors to regulate vessel formation.

Angiostatic Steroids

Composed of cortisol or tetrahydrocortisol plus heparin or $\beta$-cyclodextrin, these degrade newly formed basement membrane components of growing capillaries.

Bevacizumab

A therapeutic agent that acts as a VEGF Antibody to inhibit positively acting angiogenesis agents.

Aflibercept

A soluble VEGF receptor decoy agent used to inhibit angiogenesis.

High Interstitial Pressure

Caused by leaky vessels and lack of lymphatic drainage in tumors; this mechanical stretch stimulates cell proliferation.

Metastasis

The colonization of a tumor in sites distant from the primary mass; it is the major cause of treatment failure.

First Metastatic Cascade

Local invasion

First Step of Invasion in the Metastatic Cascade

Attachment (involving laminin and fibronectin)

Seed & Soil Hypothesis

The concept explaining the preference of specific metastatic locations based on the attachment and colonization compatibility between tumor cells and the organ environment.

Acute Leukemia

A type of leukemia characterized by the rapid proliferation of immature white blood cells known as blasts.

Chronic Leukemia

A type of leukemia where abnormal, morphologically mature white cells accumulate slowly.

ALL (Acute Lymphoblastic Leukemia)

An acute leukemia of the lymphoid lineage that is most common in children.

AML (Acute Myeloid Leukemia)

An acute leukemia of the myeloid lineage most common in adults, defined by having $>20\%$ blasts in peripheral blood or bone marrow.

CML (Chronic Myeloid Leukemia)

A chronic myeloid leukemia common in middle-aged adults, where $>95\%$ of patients possess the Philadelphia chromosome ($Ph1$) from $t(9:22)$, producing the BCR/ABL fusion protein.

CLL (Chronic Lymphocytic Leukemia)

The most common leukemia in older adults; it involves morphologically mature but immunologically immature lymphocytes and progresses from lymphocytosis to pancytopenia.

Hodgkin's Lymphoma

A neoplasm of lymphoid tissue featuring a small number of malignant B-lymphocytes admixed with a large number of inflammatory cells and fibrosis.

Non-Hodgkin's Lymphoma

A neoplasm involving the clonal expansion of B-, T-, or NK-cells or their precursors.

Multiple Myeloma (MM)

A plasma cell neoplasm involving widespread bone marrow involvement that evolves from MGUS (monoclonal gammopathy of undetermined significance).

MM End-Organ Damage Symptoms

Hypercalcemia (Calcium $\uparrow$), Renal failure, Anemia, and lytic Bone lesions.

Plasmacytoma

A single localized tumor consisting of a plasma cell neoplasm.

Second Step of Vessel Formation

Endothelial cell induced basement membrane degradation

Third Step of Vessel Formation

Endothelial cell migration

Fourth Step of Vessel Formation

Endothelial cell mitosis

Fifth Step of Vessel Formation

Lumen formation

Sixth Step of Vessel Formation

Maturation & Stabilization (recruiting pericytes/smooth muscle)

Seventh Step of Vessel Formation

Remodeling

Second Step of Metastatic Cascade

Intravasation (penetration into vessels)

Third Step of Metastatic Cascade

Circulation through the bloodstream to reach distant sites.

Fourth Step of Metastatic Cascade

Extravasation (exit from vessels) and establishment of secondary tumors.

Fifth Step of Metastatic Cascade

Colony formation at a distant site

Second Step of Invasion in the Metastatic Cascade

Proteolysis (involving metalloproteinases and uPA)

Third Step of Invasion in the Metastatic Cascade

Migration (utilizing chemotaxis factors and autocrine motility factor).

Sunitinib

A multi-targeted receptor tyrosine kinase inhibitor that blocks angiogenesis and tumor growth by inhibiting VEGFR, PDGFR, and CSF-1R.

Sorafenib

A receptor tyrosine kinase inhibitor using its mechanism of action to block both tumor cell proliferation and angiogenesis via inhibition of RAF kinase and VEGFR.

Thalidomide

An immunomodulatory drug that inhibits angiogenesis by affecting the production of TNF-alpha and promoting the degradation of pro-angiogenic factors.

Dexamethasone

A corticosteroid that exerts anti-inflammatory effects and inhibits vascular permeability, therefore reducing the growth of tumors by affecting angiogenesis.

Rapamycin (Sirolimus)

An mTOR inhibitor that blocks cell cycle progression and reduces vascular endothelial growth factor (VEGF) production, thereby inhibiting angiogenesis.

Imatinib

A specific tyrosine kinase inhibitor that targets the BCR/ABL fusion protein and inhibits cell proliferation in cancers such as CML.

Trastuzumab

A monoclonal antibody targeting HER2 receptor, inhibiting cell proliferation and angiogenesis in HER2-positive breast cancer.

Axitinib

A potent selective inhibitor of VEGFRs that works to block the pathways responsible for angiogenesis in tumors.