Cancer Biology, DNA Repair, and Targeted Therapies

Vocabulary flashcards covering topics in cancer genetics, types of DNA mutations, damage repair pathways, cellular death mechanisms, oncogenes, tumor suppressors, and targeted drug nomenclature.

Genome

The complete set of genes or genetic material present in a cell or organism.

Transition Substitution

A point mutation in which a purine or pyrimidine base is replaced by a base of the same kind.

Transversion Substitution

A point mutation in which a purine base is replaced by a pyrimidine base, or vice versa.

Silent Mutation

A base substitution that codes for the same amino acid due to the degeneracy of the genetic code, typically occurring in the third base position of a codon (wobble position).

Extrachromosomal DNA (ecDNA)

A distinct type of circular DNA that does not reside on a chromosome; in cancer cells, large Mb-sized ecDNAs are amplified and carry multiple genes and regulatory regions.

Kataegis

A pattern of localized hypermutations in cancer genomes where a large number of highly patterned base-pair mutations occur in a small region of DNA.

Chromothripsis

A phenomenon involving complex patterns of alternating gene copy number changes resulting from the catastrophic shattering of a chromosome and accidental, incomplete restoration of fragments.

Gray (Gy)

The SI unit of absorbed radiation dose representing absorbed energy per unit mass of tissue, defined as $1\,\text{Gy} = 1\,\text{Joule/kilogram} = 100\,\text{rad}$.

Linear Energy Transfer (LET)

The rate at which energy is transferred per unit length of track ($\text{keV/}\mu\text{m}$), where higher LET particles (alpha particles, protons, neutrons) induce greater biological damage than lower LET radiation.

Direct Reversal Repair (DRR)

An error-free DNA repair pathway requiring no DNA synthesis, exemplified in humans by MGMT removing $O^6$-alkylguanine adducts via a stoichiometric suicide reaction mechanism.

Base Excision Repair (BER)

A DNA repair pathway where damaged bases (such as 8-oxoG) are excised by a DNA glycosylase (OGG1) to form an AP site, followed by strand incision by APE1 and replacement via short-patch or long-patch mechanisms.

Non-Homologous End-Joining (NHEJ)

A DNA double-strand break repair pathway that directly reseals broken DNA ends and operates throughout all phases of the cell cycle.

Homologous Recombination (HR)

A double-strand break repair pathway active exclusively during the S and G2 phases of the cell cycle that uses homologous DNA sequences and key proteins such as BRCA1, BRCA2, and Rad51.

Apoptosis vs. Necrosis

Apoptosis is an active, programmed cellular dismantling process that avoids inflammation and shows cell surface blebbing, whereas necrosis is passive, accidental cell death causing plasma membrane disruption and inflammatory content release.

SH2 Domain

A modular protein region of approximately 100 amino acids that specifically binds to phosphotyrosine-containing sequences on protein tyrosine kinases and substrates.

SH3 Domain

A modular protein domain of approximately 50 amino acids that binds to target proteins containing the proline-rich consensus sequence $\text{PXXP}$.

Target of Rapamycin (TOR)

An essential eukaryotic protein kinase that integrates growth factor, energy, and nutrient signals to regulate ribosomal translation initiation and cell-cycle transition from G1 to S phase.

Nomenclature Formula for Targeted Therapies

A systematic naming convention where monoclonal antibodies end with the stem "-mab" (substems like "-ximab", "-zumab") and small molecule inhibitors end with the stem "-ib" (substems like "-tinib", "-ciclib", "-parib").

Sotorasib

An acrylamide-derived covalent small molecule inhibitor that selectively and irreversibly binds KRAS G12C in its GDP-bound state at cysteine-12, locking it in an inactive conformation.

Daraxonrasib

A first-in-class pan-RAS(ON) inhibitor that acts as a molecular glue recruiting cyclophilin A (CYPA) to active RAS-GTP complexes, physically preventing downstream effector binding.

p53 Domain Structure

The structural layout of the p53 protein consisting of an N-terminal transactivation domain/MDM2 binding site (residues 1–42), a central DNA-binding domain (102–292) containing mutational hotspots, a tetramerization domain (324–355), and a C-terminal regulatory domain (355–393).

PTEN

A 403-amino-acid tumor suppressor phosphatase that dephosphorylates PtdIns(3,4,5)P3 to negatively regulate PI3K, AKT, and mTOR signaling pathways.

pVHL

The substrate recognition component of a cullin-dependent E3 ubiquitin ligase complex that targets hydroxylated HIF-$\alpha$ subunits for proteasomal degradation under normal oxygen levels.