BCB Study Guide: Cancer Biology

Comprehensive vocabulary flashcards covering key historical experiments, tumor suppressors, oncogenes, cell cycle checkpoints, epidemiology, carcinogen classes, and metastatic mechanisms.

Theodor Boveri

Scientist who predicted in $1914$ that cancer was caused by chromosomal mutations, theorizing the existence of oncogenes and tumor suppressors.

Sidney Farber

Founder of the Jimmy Fund who pioneered the use of aminopterin (chemotherapy) to treat childhood leukemia.

Marry Lasker

Cancer advocate who reorganized the American Cancer Society and successfully lobbied to increase National Cancer Institute (NCI) funding from $\$14\text{M}$ to $\$110\text{M}$.

Gain-of-Function Mutation

Mutations that convert a normal proto-oncogene into an overactive oncogene.

Loss-of-Function Mutation

Mutations that deactivate a tumor suppressor gene, normally requiring the mutation of both genetic copies.

Ivanofsky and Beijerinck

Researchers in the $1890\text{s}$ who established virology by discovering that pathogens causing tobacco mosaic disease were filterable infectious agents.

Peyton Rous

Researcher who studied chicken sarcomas in $1911$ and showed that cell-free filtrate from diseased chickens transmitted tumors to healthy chickens, demonstrating that cancer could be transmitted by a virus.

Burkitt, Epstein & Barr

Scientists who discovered the Epstein-Barr Virus in $1964$ by culturing cells from East African childhood Burkitt's Lymphoma.

SV40 Large T Antigen

A viral oncoprotein produced by SV40 that binds and neutralizes both pRb and p53 tumor suppressors.

Human Adenovirus Oncoproteins (E1A and E1B)

Viral proteins produced by Human Adenovirus where E1A targets and inactivates pRb, and E1B targets and inactivates p53.

HPV Oncoproteins (E6 and E7)

Viral oncoproteins of Human Papillomavirus where E7 targets pRb and E6 targets p53 for inactivation.

The 4 Major Tumor Suppressors

The four central tumor suppressor proteins: pRb, p53, PTEN, and VHL.

Mechanisms of Oncogene Generation

Three mechanisms that convert a proto-oncogene into an oncogene: deletion/point mutation (hyperactive protein), gene amplification (protein overproduction), and chromosome rearrangement (moving a gene near an active regulatory sequence or creating a hyperactive fusion protein).

Classic Features of a Tumor Suppressor

Genes characterized by inactivation via loss-of-function mutations, targeted allelic loss, and predisposing individuals to cancer when inherited in mutant form.

VHL (Von Hippel-Lindau)

An oxygen sensor that tags HIF for destruction in high oxygen; in low oxygen, it permits HIF to survive and stimulate VEGF-mediated blood vessel growth.

HIF (Hypoxia-Inducible Factor)

A transcription factor destroyed by VHL that activates genes for blood vessel angiogenesis (VEGF) and glucose transport.

BRCA1/2

Tumor suppressor proteins that facilitate homologous recombination and DNA repair to resolve double-strand breaks.

NF1 (Neurofibromin 1)

A tumor suppressor that acts as a Ras off-switch by converting active Ras-GTP into inactive Ras-GDP, cutting off proliferation signals.

PI3K/Akt Pathway

A cell growth and survival switch where growth factor activation causes PI3K to produce PIP3, recruiting and activating Akt; reset by PTEN, which degrades PIP3 to shut down Akt and mTOR signaling.

INK4a (p16)

A $G_1/S$ cell cycle brake that blocks CDK4/6, keeping Rb bound to E2F and stopping the cell from entering S-phase.

ARF (p14)

An oncogene stress alarm triggered by high growth stress that blocks MDM2, allowing p53 to accumulate to halt division or trigger cell death.

p53

A homotetrameric tumor suppressor protein whose dominant-negative mutant forms can inactivate the wild-type subunits within the complex.

MDM2

An E3 ubiquitin ligase that binds directly to p53 and mediates its degradation.

INK4a/ARF Locus

A single genetic locus on human chromosome $9p21$ that uses alternative reading frames to produce two entirely distinct tumor suppressors (p16INK4a and p14ARF).

Temin & Baltimore

Researchers who discovered reverse transcriptase and the life cycle of RNA tumor viruses, initially proposing that oncogenes had a strictly viral origin.

Bishop & Varmus

Scientists who discovered that the v-src oncogene was dispensable for viral replication, proving oncogenes originate from cellular proto-oncogenes hijacked and mutated by retroviruses.

mTOR

The cell's master nutrient and growth regulator that senses amino acids, ATP, and growth signals; acts through mTORC1 downstream of Akt/Rheb to activate protein synthesis (via S6K and 4E-BP1) and inhibit autophagy.

Restriction Point

The point of no return located between early $G_1$ and late $G_1$, marking the transition where a cell shifts from growth factor-dependent signaling to growth factor-independent division commitment.

ATM Kinase

A kinase that senses DNA double-strand breaks and coordinates repair signaling by phosphorylating targets including p53, CHK2, BRCA1, and NBS1.

Caspases

Protease enzymes (such as Caspase-$8$, $-9$, $-3$, $-6$, and $-7$) that cleave specific cellular substrates to execute apoptosis.

Death Receptors

Transmembrane surface proteins (such as Fas and DR5) that bind extracellular death ligands to activate Caspase-$8$ via the extrinsic apoptotic pathway.

Spindle Checkpoint

An M-phase monitoring mechanism regulated by BUB1 and MAD2 that ensures proper chromosome alignment on the mitotic spindle apparatus before division can proceed.

Penetrance

The likelihood that an individual with a specific genotype (such as a BRCA mutation) will manifest the physical disease phenotype.

Cohort Study

An epidemiologic study design that follows an initially disease-free population forward over time to measure disease rates relative to specific exposures.

Case-Control Study

An epidemiologic study where individuals with a disease (cases) are compared to individuals without the disease (controls) to determine prior exposure histories.

Kin-Cohort Study

An epidemiological method that uses family histories of mutation carriers versus non-carriers to calculate penetrance.

High-Risk Cancer Variants

Rare genetic mutations ($<1\%$ allele frequency) in genes such as TP53, BRCA1, and PTEN that confer large increases in relative cancer risk (up to $10\times$).

Low-Risk Cancer Variants

Common genetic variations (up to $50\%$ allele frequency in the population) in genes like FGFR2 and CASP8 that marginally increase relative cancer risk ($\sim 1.1\times$).

MYCN Amplification

A genetic alteration in neuroblastoma absent in benign tumors ($0\%$) but present in $31\%$ of Stage $3/4$ tumors, which reduces the $3$-year survival rate from $90\%$ down to approximately $30\%$.

Pharmacogenomics

The study of how a patient's specific single nucleotide polymorphisms (SNPs) affect their physiological response, balancing drug efficacy against adverse toxicity.

Sporadic Cancer

Cancers comprising $70\text{–}80\%$ of cases, caused by random lifetime somatic mutations, characterized by late onset (ages $60\text{–}70\text{s}$), unilateral presentation, and no family history.

Familial Cancer

Cancers comprising $15\text{–}20\%$ of cases, characterized by increased clustering in families without a defined single-gene Mendelian inheritance pattern.

Inherited/Germline Cancer

Cancers comprising $5\text{–}10\%$ of cases, caused by highly penetrant inherited mutations, characterized by early onset ($<50\text{s}$), multiple affected generations, and bilateral or clustered tumors.

Ames Test

A bacterial assay that detects chemical mutagenicity by measuring reversion to a $\text{His}^+$ phenotype, limited by differences in DNA repair and metabolism between bacteria/rats and humans.

Genotoxic Carcinogens

Carcinogenic agents that directly damage DNA structure, induce strand breaks, or impair DNA repair mechanisms.

Non-Genotoxic Carcinogens

Agents that promote cancer without causing direct DNA breaks, acting via epigenetic modifications, oxidative stress, chronic inflammation, or hormone receptor modulation.

Percival Pott

British physician who in $1775$ identified the first recognized occupational carcinogen by linking chimney soot exposure to scrotal cancer in chimney sweeps.

IARC Carcinogen Classification Groups

Categorization of carcinogens: Group 1 (carcinogenic to humans), Group 2A (probably carcinogenic), Group 2B (possibly carcinogenic), and Group 3 (not classifiable).

Basement Membrane

A stiff extracellular matrix barrier ($>1000\,\text{kPa}$) composed of Collagen IV, laminin, and proteoglycans separating epithelial cells from the stroma.

Adenoma

A benign epithelial tumor characterized by neoplastic glandular tubules fully contained within a fibrous connective-tissue capsule.

Adenocarcinoma

A malignant epithelial tumor in which neoplastic gland tubules become invasive and penetrate through the capsule into the surrounding stroma.

Anoikis

A form of integrin-mediated cell death initiated via Caspase-$8$ recruitment when detached epithelial cells lose integrin ligation to the extracellular matrix.

Epithelial-Mesenchymal Transition (EMT)

A biological process wherein polarized epithelial cells lose apical-basal polarity and intercellular adhesion, replace cytokeratin with actin/vimentin, and acquire a migratory mesenchymal phenotype.

Leader Cells

K14/actin-positive, highly polarized cells that navigate at the invasive front during collective tumor cell migration.

Intravasation

The process by which cancer cells actively penetrate through the basement membrane and enter into blood or lymphatic vessels.

Extravasation

The process where circulating tumor cells lodge within distant capillary beds and invade outward into target host organ tissues.

The Five Horsemen of Cancer

The five essential genetic pathways altered in malignant transformation: pRb, p53, hTERT/telomerase, PP2A, and Ras.

Cellular Senescence

A protective state of permanent replicative arrest where damaged cells permanently cease division while remaining metabolically active and secreting tumor-promoting factors.

Replicative Immortality (Human vs. Mouse)

Mouse cells require only the loss of Arf or p53 to immortalize; human cells require the loss of both pRb and p53 to bypass $M_1$ senescence and the activation of telomerase to bypass $M_2$ crisis.

Telomeric T-Loops and D-Loops

Higher-order terminal DNA loops stabilized by TRF1 and TRF2 that hide chromosome ends from being recognized as double-strand breaks by ATM kinase.

Fusion-Bridge-Translocation-Breakage Cycle

A cycle of genomic devastation occurring when depleted telomeres undergo Non-Homologous End Joining (NHEJ) to form dicentric chromosomes that tear apart during anaphase.

Bill Hahn Five-Hit Experiment

An experimental protocol demonstrating that transforming normal human diploid fibroblasts requires five distinct genetic alterations: Large T (targeting p53 and Rb), small t (targeting PP2A), hTERT, and oncogenic Ras.

Heterotypic Tumor Microenvironment

The ecological tumor architecture composed of neoplastic cancer cells surrounded by fibroblasts, infiltrating immune cells, endothelial vessels, and extracellular matrix.