lectures 14-15 rough points

Tumor heterogeneity definition

The condition where different cells within the same tumor have different mutations from each other, making treatment difficult

Why cells in the same tumor diverge genetically

Each time a cancer cell divides it can introduce new random mutations, so daughter cells accumulate different mutations over time and become genetically distinct from each other

Why tumor heterogeneity makes cancer hard to treat

A drug designed to target one specific mutation will kill cells carrying that mutation but leave surviving cells with different mutations free to keep growing and take over

Pyrimidine dimer

An abnormal covalent bond that forms between two T or two C bases sitting next to each other on the same DNA strand when hit by UV light

How a pyrimidine dimer causes a permanent mutation

When repair enzymes try to fix the dimer they sometimes make an error and permanently convert the original C bases into T bases, changing the DNA sequence

Why UV damage is dangerous even if repair happens

The repair process itself is error prone, meaning the attempt to fix the damage can introduce a new permanent mutation rather than restoring the original sequence

Why UV causes a specific signature mutation

Because pyrimidine dimers specifically involve C and T bases, UV damage tends to cause C to T conversions which is a recognizable pattern in skin cancer mutations

One drug cannot cure a heterogeneous tumor because

Different cells in the tumor have different mutations, so a drug targeting one mutation kills some cells but leaves other cells with different mutations alive to continue growing

Selective pressure in tumors

When a drug kills most cancer cells but misses cells with different mutations, those surviving cells reproduce and the tumor regrows as a drug resistant population

Why doctors sometimes use multiple drugs simultaneously

To target several different mutations at once, reducing the chance that any single cell survives because it happens to lack the targeted mutation

Contact inhibition

The normal property of healthy cells where they only divide when they are physically connected to and in contact with neighboring cells

Cell cell adhesion genes

Genes that code for the anchor proteins connecting cells to their neighbors; when these are mutated cancer cells lose their physical connections and the division signal that comes with them

Why losing cell adhesion leads to both uncontrolled division and metastasis

Without anchor proteins the cell no longer receives the contact signal required to stay in G0, so it divides uncontrollably, and without physical anchors it can also break free and travel to new locations

How metastasis mechanistically begins

Mutations in cell cell adhesion genes cause cancer cells to lose the proteins that physically hold them in place, allowing them to detach from the original tumor and enter the bloodstream or lymph system

What DNA repair genes normally do

They encode the enzymes that constantly scan DNA for damage and fix mismatches, chemically damaged bases, and thymine dimers before they become permanent mutations

Why losing DNA repair function is especially dangerous

Without working repair enzymes, every source of DNA damage including normal oxygen metabolism and background radiation leads to permanent mutations instead of being corrected

Why a DNA repair gene mutation accelerates all other mutations

Once repair is broken, mutations accumulate much faster across the entire genome, meaning checkpoint genes and tumor suppressor genes are much more likely to get hit by subsequent mutations

The cascade effect of broken DNA repair

Broken repair leads to more mutations, more mutations means checkpoint genes get damaged, damaged checkpoints means even more errors get through, creating a self accelerating cycle toward cancer