Exam 1 Groupme Cards

What are the 10 hallmarks of cancer

1. Uncontrolled proliferation

2. uncontrolled growth

3. abberant telomere length vs replication

4. resistance to cell death

5. angiogenesis

6. invasion adn metastatis

7. dysregulation of metabolism

8. tumor promoting inflammation

9. genome instability and mutation

10. avoiding immune detection

Which cancer hallmark is this describing?

• continuous “go” signals through growth factors, receptors, or downstream pathways such as Ras and PI3K

sustaining proliferative signaling

Which cancer hallmark is this describing?

• escape from antiproliferative controls, especially RB and p53 pathways

evading growth supressors

Which cancer hallmark is this describing?

• avoidance of apoptosis and other death programs, often involves excess anti-apoptotic BCL-2 activity

resisting cell death

Which cancer hallmark is this describing?

• maintenance of telomeres, usually by telomerase, so cells can keep dividing

enabling replicative immortality

Which cancer hallmark is this describing?

• recruitment of blood vessels, often through VEGF, to supply oxygen and nutrients

inducing angiogenesis

Which cancer hallmark is this describing?

• local tissue invasion and colonization of distant organs

activating invasion and metastasis

Which cancer hallmark is this describing?

• metabolic reprogramming that supports rapid growth and biomass production

deregulating cellular energetics

Which cancer hallmark is this describing?

• escape from immune recognition or elimination

avoiding immune destruction

Which cancer hallmark is this describing?

• higher mutation and chromosome error rates generate variants that selection can act upon

genome instability and mutation

Which cancer hallmark is this describing?

• inflammatory cells and signals provide growth and survival, angiogenic, and invasive support

tumor-promoting inflammation

What are three major pathways to tumorigenesis

RB: cell cycle entry

Ras: signaling cascade that drives cell growth

P53: tolerance to stress and DNA

What are telomeres? What is telomerase? How do they function within a normal cell? How do these contribute to tumorigenesis?

• telomere: dna sequences at the ends of chromosomes

• telomerase: enzyme that helps maintain them

• Every time a normal cell divides, telomeres shorten until it reaches senescence.

• Telomerase contributes to tumorigenesis by extending telomeres, which allows cancer cells to bypass senescence and achieve unlimited cell division

(if your confused watch a youtube video about how they contribute to tumorigenesis)

What are some examples of how genetic and epigenetic mechanisms promote evolution of cancer

1. an oncogene becomes activated, increasing cell proliferation

2. a tumor suppressor gene becomes inactivated, removing a cell cycle checkpoint

3. the cell develops resistance to apoptosis

4. DNA repair defects increase genomic instability

5. additional mutations can create new subpopulations of tumor cells

6. cells with the greatest survival and reproductive advantages exapnd through clonal selection

Def of epithelial cancers. Def of carcinoma. Some examples of epithelial cancers.

• Epithelial: Cancer that covers body surfaces, organs, glands, and body cavities.

• Carcinoma: a malignant tumor originating from epithelial cells

1. skin

2. breast

3. lung

4. colon

5. prostate

6. cervix

What is the difference between a carcinoma and adenocarcinoma

An adenocarcinoma is a carcinoma (epithelial cancer) that develops from glandular or secretory cells.

(basically a cancer with secretory functions)

What are some examples of adenocarcinomas

1. breast

2. lung

3. colon

4. prostate

5. pancreas

What are neuroectodermal cancers

• includes certian nervous system derived cancers

1. gliomas

2. astrocytomas

3. neuroblastomas

what are mesodermal cancers?

A malignant tumor originating from these CT’s are called ______

• cancer of tissues such as bone, muscle, CT, cartilage, fat, and blood vessels.

• sarcomas

What are hematopoietic cancers

• cancers arising from blood-forming cells

What type of hematopoietic cancer is this

• cancer of blood forming cells, commonly involving bone marrow and blood

leukemia

What type of hematopoietic cancer is this

• cancer of lymphocytes that commonly form masses in lymphatic tissue

lymphoma

What type of hematopoietic cancer is this

• cancer of antibody producing plasma cells

myeloma

Some known or suspected carcinomas

• vinyl chloride

liver angiosarcoma

What type of hematopoietic cancer is this

• benzene

acute leukemias

Some known or suspected carcinomas

• arsenic

skin carcinomas and bladder cancer

Some known or suspected carcinomas

• asbestos

mesothelioma

Some known or suspected carcinomas

• radium

osteosarcoma

Some known or suspected carcinomas

• aflatoxin B1

liver cancer

The professor specifically points out aflatoxin B1.

1. What is the source of this carcinogen?

2. associated with what type of cancer

1. Produced by mold from improperly stored grains/peanuts

2. liver cancer

Why can a chemical that enters the body become carcinogenic after metabolism?

Because metabolic processing can convert a relatively inactive compound into a reactive compound that damages dna

Chromosome segregation and nuclear division occur during _____.

mitotis

What is this chromosome abnormality?

• gain or loss of a whole chromosome

aneuploidy

(n+1) (n-1)

What is this chromosome abnormality?

• catastrophic chromosome shattering & abnormal reassembly

chromothripsis

What is this chromosome abnormality?

• formation of multiple copies of a gene or chromosome region

gene amplification

What is this chromosome abnormality?

• a chromosome segment becomes joined to another chromosome

(think philadelphia chromosome (p9+p21)

translocation

What is this chromosome abnormality?

• structural reorganization such as deletion, inversion, duplication or translocation

chromosome rearrangement

In terms of genetic and genomic instability, what happens if…

• defective DNA repair

mutations remain in the genome and are passed on to daughter cells

In terms of genetic and genomic instability, what happens if…

• loss of cell cycle checkpoints

Damaged cells progress through the cell cycle. Some important proteins are p53, p21, Rb, and p16.

In terms of genetic and genomic instability, what happens if…

• chromosome segregation errors occur

during mitosis, errors can occur that involve a lagging or improperly attached chromosome, leading to aneuploidy or chromothropsis

In terms of genetic and genomic instability, what happens if…

• telomere dysfunctions

critically short telomeres can cause chromosome ends to fude and this can lead to repeated cycles of fusion

In terms of genetic and genomic instability, what happens if…

• regulation stress

rapid proliferation can cause DNA to stall or fail, further leading to DNA breaks and deletions

What are oncogenes and what do they do.

Activated versions of proto-oncogenes that drive excessive growth or survival.

• involves GAIN OF FUNCTION mutations

The professor stated dominant and recessive cancer mutations. Between oncogenes and tumor suppressor genes, which one is dominant and which one is recessive and why.

ONCOGENES: involves and gain of function and only one is required, so it is considered to be dominant.

TUMOR SUPPRESSOR GENES: typically require both tumor suppressor alleles, so it is recessive.

Oncogenes involve ___ while tumor suppressor genes involve ___

Oncogenes involve a gain of function mutation

Tumor suppressor genes lead to a loss of function/protection

What is this?

• tumor supressor gene

• “guardian of genome”

• regulates cell cycle arrest, dna repair, senescence and apoptosis

p53

What is this?

• tumor supressor gene

• regulates cell cycle and controls G1→S phase by inhibiting E2F transcription

• maintains cells in G1 (resting) phase

• guardian of the genome

RB

What is this?

• proto-oncogene

• involved with cell growth

• part of MAPK/ERK pathway

• transmits signals from GF receptors to nucleus

RAS

What is this?

• proto-onogene

• transcription factor

• regulates genes involve din cell growth and proliferation

MYC

In simple terms what protooncogene is this

• gives signal-growth

RAS

In simple terms what proto-oncogene is this

• Makes more- multiplies

MYC

In simple terms what proto-oncogene is this

• protects-prevents

p53

In simple terms what proto-oncogene is this

• restraining-blocks cell cycle

Rb

really study this

HPV is associated with what cancers

• warts

• cervical carcinoma

• orophayngeal cancer

Mechanism for HPV and how it causes cancer

• viral proteins E6 interferes with p53, reducing cell cycle arrest and apoptosis

• E7 interferes with Rb, releasing E2F and encouraging entry into S phase

What cancer is HIV associated with

Kaposi’s sarcoma

HIV cancer mechanism

• this autoimmune disease causes immune supression and reduces control of oncogenic viruses and abnormal cells

What cancers are associated with H pylori

• gastric adenocarcinoma

H.pylori mechanism

• some strains contain CagA capable of disrupting epithelial cell polarity

What cancer is HCV associated with and its mechanism (Hep C)

associated with liver cancer and hepatocellular carcinoma

• chronic liver inflammation, liver injury and cirrhosis

What is quiescence

A TEMPORARY and REVERSIBLE state of arrest. Can re enter the cycle when it recieves appropriate mitogens/GF

when does differentiation occur

• occurs when a cell becomes specialized to perform a specific function and then leaves the cell

what is endoreplication

• when a cell replicates its DNA but does NOT DIVIDE, it therefore accumulates additional chromosomes to produce a polyploid cell

What is senescense

A STABLE and PERMANENT cell cycle arrest caused by cellular stress such as DNA damage, hypoxia, chemo, telomere shortening, etc.

• Important to note: remains dormant and active. May release inflammatory substances (SASP) that promote inflammation and tumor progression

If senescent cells are linked to cancer pogression, why not use drugs to eliminate them?

Senescent cells are also involved in tissue healing. Killing all senescent cells may impair tissue repair.

DO senescent cells respond to mitogens

NO. unable to reactivate the E2F transcriptional program needed for cell cycle entry and DNA replication

In the hallmarks of senescence, explain the tumor suppressor pathway steps

1. stress activates p53

2. p53 stimulates p21 production

3. p21 inhibits cyclin-CDK complexes (primary molecular engines that drive cells forward through the different phases of the)

4. RB remains active and suppresses E2F (a family of proteins that control how cells grow, divide, and copy their DNA)

5. Cell remains arrested

how do p16 and RB work together to keep senescent cells out of cycle

1. p16INK4a blocks CDK4/6

2. with CDK4/6 blocksd, RB stays active.

3. RB prevents E2F from activating S-phase genes

4. Cell cannot re-enter the cycle

What are quiescent triggers

• lack of GF or nutrients, or a need to divide

what are senescent triggers

DNA damage, telomere shortening, oncogene activation, stress

if senescent cells cannot re-enter the cell cycle, how can they cause cancer?

• Secreting Inflammatory Factors (SASP): Senescent cells release a cocktail of cytokines, growth factors, and enzymes (such as matrix metalloproteinases) into nearby tissue.

• Fueling Angiogenesis: The secreted SASP factors stimulate the creation of new blood vessels, supplying nearby precancerous or malignant cells with the oxygen and nutrients they need to grow.

• Driving Cell Invasion and Metastasis: Chemical signals from senescent cells break down the extracellular matrix, making it easier for neighboring cancer cells to invade surrounding tissues and spread to other parts of the body.

• Promoting Immune Evasion: The chronic inflammatory barrier created by senescent cells can block or exhaust immune cells, shielding nearby cancer cells from being detected and destroyed

what are three common cell death programs important for eliminating cancer cells

1. apoptosis

2. autophagy

3. ferroptosis

What is apoptosis

• programmed cell death that removes damaged or infected cells without producing an inflammatory responce

Apoptosis has intrinsic and extrinsic pathways. What triggers them and role of mitochondria.

INTRINSIC

• triggered by internal stress like dna damage, oncogene stress, chemo.

• mediated by mitochondria

EXTRINSIC

• triggered by extracellular signals binding to surface cell death receptors (FAS)

• no mitochondria required

What triggers apoptosis intrinsic

• dna damage, oncogene stress, chemo

What is autophagy

• self eating

• intracellular recycling system that uses autophagosomes to engulf damaged organelles and delivers components to lysosomes for degredation and reuse

how can autophagy suppress cancer

removing damaged mitochondria, limiting oxidative stress, and preventing accumulation od damaged proteins

how can autophagy be both beneficial and detrimental

BENEFICIAL: removes damaged mitochondria which prevents acumulation of damaged proteins

DETRIMENTAL: cancer cells use autophagy to survive nutrient deprivation and low oxygen. They can also recycle cellular materual for energy

what is ferroptosis

• cell death caused by iron dependent accumulation of lethal lipid peroxides in cell membrane

how does ferroptosis help with the development of cancer

• some cancer cells are vulnurable to ferroptosis due to high iron requirements.

• some cancer therapies induce ferroptosis to kill cancer cells that resist apoptosis, basically functioning as a tumor supressor mechanism

if chromo 9 and 22 undergo translocation, this would produce the _____ fusion, and cause ___ ___ ___

BCR-ABL; chronic myelogenous leukemia (cml)

what drug blocks BCR_-ABL

imatinib (gleevec)

A chromosomal translocation creates BCR-ABL. What disease is associated with this alteration?

CML

what is the main idea behind ferroptosis

iron-dependent accumulation of lipid hydroperoxides to lethal levels

what is Bcl-2?

anti-apoptotic protein

An increased level of Bcl-2 means what?

decreased levels of apoptosis, contributing to cancer

what is bh3

a drug that inhibits Bcl-2 anti-apoptotic proteins