CancerCancer

A Disease Resulting from A Disease Resulting from Uncontrolled Cell Growth Uncontrolled Cell Growth

Due to lack of specialization, Due to lack of specialization, cancer cells have a cancer cells have a different appearance different appearance than surrounding cells.than surrounding cells.

Cancer cells have enlarged nuclei and may have extra chromosomes.Cancer cells have enlarged nuclei and may have extra chromosomes.They are genetically unstable and accumulate mutations.They are genetically unstable and accumulate mutations.

Normal cervical cellsNormal cervical cells Precancerous Precancerous cervical cellscervical cells

Cancerous Cancerous cervical cellscervical cells

Properties of Cancer Cells

Non-cancerous Non-cancerous cells form sheets.cells form sheets.

Cancer cells grow Cancer cells grow into tumors, into tumors, showing a lack of showing a lack of contact inhibition.contact inhibition.

Cancer cells do not respond to signals from Cancer cells do not respond to signals from Growth factors—stimulate or inhibit cell division Growth factors—stimulate or inhibit cell division Apoptosis factors—promote death of cells Apoptosis factors—promote death of cells with damaged DNA with damaged DNA

Properties of Cancer Cells

Cancer cells divide more frequently and for an Cancer cells divide more frequently and for an unlimited number of times due to an abundanceunlimited number of times due to an abundanceof telomerase, an enzyme that repairs the ends of telomerase, an enzyme that repairs the ends of chromosomesof chromosomes

Cancer cells show metastasis, an invasion of Cancer cells show metastasis, an invasion of other tissuesother tissues

Angiogenesis: cancerous tumors grow new blood Angiogenesis: cancerous tumors grow new blood vessels for delivery of nutrients and oxygen vessels for delivery of nutrients and oxygen

Properties of Cancer Cells

Cancer is the result of multiple mutations Cancer is the result of multiple mutations causing uncontrolled growthcausing uncontrolled growth

Angiogenesis: Formation of new Angiogenesis: Formation of new blood vessels, allows tumor to blood vessels, allows tumor to grow to larger sizegrow to larger size

Normal Cell Growth Involves Normal Cell Growth Involves the Cell Cycle with Mitosisthe Cell Cycle with Mitosis

G1cytoplasm doubles

S

chromosomesreplicate

G2assembly of components for division cytokinesis

P MA

T

Mitosis

Mitosis includesMitosis includesP = prophaseP = prophase

M = metaphaseM = metaphaseA = anaphaseA = anaphaseT = telophaseT = telophase

Interphase includesInterphase includesG1 = growth phase 1G1 = growth phase 1

S = synthesis phaseS = synthesis phaseG2 = growth phase 2G2 = growth phase 2

Interphase

Mitosis = Chromosomal Division Leading to Genetically Mitosis = Chromosomal Division Leading to Genetically Identical NucleiIdentical Nuclei

Chromosomes align individually

at the cell equator so each daughter cell receives one

copy of each chromosome

Control of the Cell CycleControl of the Cell Cycle

Mechanisms for controlling progress Mechanisms for controlling progress through the cell cyclethrough the cell cycleExtracellular Signals Extracellular Signals

Control the timing of cell division Control the timing of cell division TransitionsTransitions

Orderly progression from one stage of cell Orderly progression from one stage of cell cycle to anothercycle to another

Depend on the production of proteins Depend on the production of proteins called cyclinscalled cyclins

CheckpointsCheckpointsDelay progression to next stage if cell Delay progression to next stage if cell

must repair damage must repair damage

Control of the Cell Cycle Involves Control of the Cell Cycle Involves Activities at Transitions and Checkpoints Activities at Transitions and Checkpoints

G1S

G2

cytoplasm doubles

chromosomesreplicate

assembly of components for division cytokinesis

P MA

TMitosis

G1G1S S TransitionTransition

G2G2M M CheckpointCheckpoint

DNA DamageDNA DamageCheckpointCheckpoint

ApoptosisApoptosisCheckpointCheckpoint

G2G2M M TransitionTransition Spindle Spindle

AssemblyAssemblyCheckpointCheckpoint

G1G1S S CheckpointCheckpoint

SSG2G2TransitionTransition

Signals initiate self-destruction if DNA damage is

severe

Cancer-Causing Mutations Occur in Two Types of GenesCancer-Causing Mutations Occur in Two Types of Genes

Proto-oncogeneProto-oncogenestimulates cell divisionstimulates cell division

OncogeneOncogeneoverstimulates cell divisionoverstimulates cell division

mutationmutation

Tumor Suppressor GeneTumor Suppressor Geneinhibits cell divisioninhibits cell division

Mutated Tumor Suppressor GeneMutated Tumor Suppressor Genecannot influence cell cyclecannot influence cell cycle

mutationmutation

Mutations That Cause CancerMutations That Cause Cancer

Gene Gene TypeType

Normal Normal FunctionFunction

In CancerIn Cancer Mutation Mutation TypeType

Proto-Proto-OncogeneOncogene

In response to In response to extracellular or extracellular or

intracellular intracellular signals, promotes signals, promotes cell division and cell division and

prevents prevents apoptosisapoptosis

OncogeneOncogene

Promotes cell Promotes cell division in division in absence of absence of

signalssignals

DominantDominant

Tumor Tumor Suppressor Suppressor

GeneGene

Inhibits cell Inhibits cell division and division and

promotes promotes apoptosisapoptosis

Active gene Active gene product no product no

longer longer available to available to control cell control cell

divisiondivision

RecessiveRecessive

exampleexampleRasRas

examplesexamplesRBRBp53p53

Ras Proto-OncogeneRas Proto-Oncogene

In response to growth factor binding at receptor, the Ras gene product combines with GTP to promote cell division

In cancer cells, the RAS gene product is locked into its GTP-binding shape and does not require a signal at

the receptor in order to stimulate cell division

In Normal Cells, the Rb Gene Product In Normal Cells, the Rb Gene Product

Controls the G1Controls the G1 S Transition S Transition RB = product of

Retinoblastoma gene, inhibits action of E2F until chemically modified due to buildup of CDK-cyclins

(intracellular signals)

In people who are heterozygous for a mutation in the RB gene (RbIn people who are heterozygous for a mutation in the RB gene (Rb++RbRb--), ), there is a tendency for the functional copy of the RB gene (Rbthere is a tendency for the functional copy of the RB gene (Rb++) to mutate ) to mutate

to Rbto Rb--. Retinal cancer develops because growth of tumor cells is no . Retinal cancer develops because growth of tumor cells is no longer controlled at the the G1longer controlled at the the G1S transition.S transition.

E2F = transcription factor required to activate genes

for DNA synthesis

In Normal Cells, the p53 Gene Product In Normal Cells, the p53 Gene Product Acts at the G1Acts at the G1 S Checkpoint Preventing S Checkpoint Preventing

Entry Into S Phase If DNA Is DamagedEntry Into S Phase If DNA Is Damagedp21 inhibits intracellular signals

that would activate E2F

p53 = transcription factor that causes p21 to be produced

Cells with damaged DNA do not pass the

G1S checkpoint

In cancer cells the mutated p53 gene product no longer stimulates p21

production. Cells will pass the G1 S checkpoint even when chromosomal

damage exists.

In Normal Cells, the p53 Gene Product Stimulates In Normal Cells, the p53 Gene Product Stimulates Apoptosis If DNA Damage Cannot Be RepairedApoptosis If DNA Damage Cannot Be Repaired

p53 gives an internal signal for apoptosis

In cancer cells, a mutated p53 gene product no longer initiates

self-destruction. Cells with damaged DNA can divide and

more DNA damage can be accumulated.

p53 is the most frequently mutated of all known cancer-causing genes, contributing to many types of cancer.

Causes of CancerCauses of Cancer

• HeredityHeredity– tendency to develop cancer can be tendency to develop cancer can be

inherited due to mutations in tumor inherited due to mutations in tumor suppressors, such as BRCA1 and RBsuppressors, such as BRCA1 and RB

– Tendency to inherit thyroid cancer is Tendency to inherit thyroid cancer is linked to the RET proto-oncogenelinked to the RET proto-oncogene

• Environmental CarcinogensEnvironmental Carcinogens– agents that contribute to cancer agents that contribute to cancer

development, often by causing development, often by causing mutationsmutations

Causes of CancerCauses of Cancer• Environmental CarcinogensEnvironmental Carcinogens

– RadiationRadiation• ultraviolet radiation in sunlightultraviolet radiation in sunlight• nuclear radiationnuclear radiation• radon gasradon gas

– Organic chemicals found in Organic chemicals found in • tobacco smoketobacco smoke• pollutantspollutants

– VirusesViruses• hepatitis B and C viruseshepatitis B and C viruses• Epstein-Barr virusEpstein-Barr virus• human papillomavirushuman papillomavirus• HIVHIV

Cancer PreventionCancer Prevention• Protective BehaviorsProtective Behaviors

– Avoid CarcinogensAvoid Carcinogens– Get regular screening testsGet regular screening tests– Get vaccinatedGet vaccinated

• Dietary HabitsDietary Habits– Avoid excess weight gainAvoid excess weight gain– Exercise regularlyExercise regularly– Exclude foods that promote cancer– Exclude foods that promote cancer–

salt-cured or smoked foods, excess salt-cured or smoked foods, excess alcoholalcohol

– Limit foods that are high in saturated fatLimit foods that are high in saturated fat– Include protective foods with fiber, Include protective foods with fiber,

vitamins A and C, and cruciferous vitamins A and C, and cruciferous vegetablesvegetables

Treatment of CancerTreatment of Cancer• Traditional TherapiesTraditional Therapies

– SurgerySurgery– RadiationRadiation– ChemotherapyChemotherapy

• restore immune function with bone marrow transplantsrestore immune function with bone marrow transplants

• Newer TherapiesNewer Therapies– ImmunotherapyImmunotherapy– p53p53 gene therapy gene therapy

• Genetically-engineered adenovirus that can infect and Genetically-engineered adenovirus that can infect and kill p53-deficient cancer cells kill p53-deficient cancer cells

– Antiangiogenic drugs to inhibit blood vessel Antiangiogenic drugs to inhibit blood vessel formationformation

– Targeted therapy acting on specific moleculesTargeted therapy acting on specific molecules• Herceptin blocks growth factor receptors on breast Herceptin blocks growth factor receptors on breast

cancer cellscancer cells• Gleevec inhibits the action of a faulty tyrosine kinase Gleevec inhibits the action of a faulty tyrosine kinase

related to uncontrolled bone marrow cell reproduction related to uncontrolled bone marrow cell reproduction in Chronic Myelogenous Leukemiain Chronic Myelogenous Leukemia