Molecular Aspects of Cancer

A collection of flashcards summarizing key concepts and facts from the lecture on the molecular aspects of cancer.

What are the original Hallmarks of Cancer (2000)?

Self-sufficiency in growth signals, insensitivity to inhibitory signals, altered metabolism, evasion of apoptosis, limitless replication, angiogenesis, metastasis, immune evasion.

What growth factors are mitogenic?

PDGF, EGF

What is an example of a growth-inhibitory factor?

TGF-β

What does PDGF do?

Stimulates division in connective tissue and nervous system development.

What family does EGFR belong to?

ErbB family of Receptor Tyrosine Kinases (RTKs).

Why are RTK mutations oncogenic?

They cause sustained proliferative signaling.

What is the Restriction (R) point?

The point at which a cell commits to division.

Which CDKs target pRB?

CDK4/6 (before R) and CDK2 (after R).

What happens when RB1 is inactivated?

Cells evade growth suppression, contributing to cancer.

What does mismatch repair (MMR) fix?

Mismatch repair (MMR) fixes replication errors that are not corrected by DNA polymerase, such as base-base mismatches and insertion-deletion loops that occur during DNA replication. This process involves the recognition of the mismatch by MMR proteins, excision of the erroneous DNA segment, and resynthesis of the correct DNA sequence, thereby maintaining

What is Lynch Syndrome?

A hereditary condition caused by defective MMR, increasing cancer risk.

Which proteins are involved in MMR?

MutS (MSH2/MSH6), MutL (MLH1/PMS2).

What is microsatellite instability (MSI)?

Microsatellite instability (MSI) is a condition of genetic hypermutability that results from the loss of DNA mismatch repair (MMR) capability. It is characterized by alterations in the length of microsatellites, which are short, repetitive sequences in the genome. Excessive mutation rates in these regions can indicate a higher likelihood of developing certain cancers, particularly colorectal cancer. MSI is considered a significant biomarker for MMR deficiency, which may suggest a potential response to immunotherapy treatments, such as immune checkpoint inhibitors

What does the DDR pathway do?

Signals and coordinates response to DNA damage.

What are examples of direct DNA repair?

Photolyase, Methyltransferase, Oxidative demethylase.

What is BER?

Base Excision Repair – fixes small lesions like oxidative damage.

What is NER?

Nucleotide Excision Repair – removes bulky lesions like UV damage.

What is HR?

Homologous Recombination – error-free repair using sister chromatid.

What is NHEJ?

Non-Homologous End Joining – quick, error-prone DSB repair.

What causes Xeroderma Pigmentosum?

Defective NER genes (e.g., XPA, XPC, XPB).

What does BRCA1 do?

Links DNA damage sensing to repair.

What does BRCA2 do?

Recruits RAD51 for homologous recombination.

What happens when ATM is mutated?

Leads to Ataxia Telangiectasia with cancer and neurological risks.

What stimulates Cyclin D expression?

Mitogen signaling through RTKs.

What are the CDK-cyclin pairs by phase?

G1: Cyclin D/CDK4/6, G1–S: Cyclin E/CDK2, S: Cyclin A/CDK2, G2–M: Cyclin B/CDK1.

What are the main CDK inhibitors?

INK4 (e.g., p16) and Cip/Kip (e.g., p21).

How do Cyclin Kinase Inihibitors work?

Block cyclin-CDK ATP-binding site, halting kinase activity.

What is the main takeaway about cancer cell cycles?

Cancer results from deregulation of cell cycle and loss of control by checkpoints.