Cancer I: Biology, Epidemiology, & Risk Factors (2)

KIN 3535 Final Exam (3)

Cancer

a term for diseases in which abnormal cells divide without control and can invade nearby tissues; Can also spread to other parts of the body through the blood and lymph systems

Neoplasia

is new, growth of cells that is not under physiologic control

Neoplasm

tumor (benign or malignant)

Metastasis

Cancer cells break off from the tumor where they originated, travel through the bloodstream or lymph vessels, and establish new tumors in distant sites

spread of cancer to distant tissue(s)

• named after original tumor site

• e.g., metastatic prostate cancer in the spine is correct, NOT calling it spine cancer

crab

What is cancer in Greek?

Oncos

mass/swelling in Greek

Melanoma

arise from melanocytes in the skin

Carcinomas

arise from epithelial tissues (i.e., tissues that line organs)

• 80-90% of all cancer cases

• Adenocarcinoma and squamous cell carcinoma (e.g., prostate, lung, colon)

Sarcomas

arise from connective tissues (e.g., bone, muscle)

• more common in young adults

• supportive and connective tissues such as bones (osteosarcoma), tendons, muscle (rhabdomyosarcoma), cartilage, and fat (liposarcoma)

Hematologic malignanices

• Cancer of the blood, blood forming cells, and lymphatic system

• Leukemia, lymphomas, myeloma

Brain and spinal cord cancers

CNS tumors

• Gliomas (astrocytomas, oligodendrogliomas, ependyomas)

• Meningiomas

• Medulloblastoma

• Schwannomas

Leukemia

• can be acute or chronic

• caused by immature or not fully functional white blood cells in bone marrow (same regardless of type of leukemia)

• they proliferate negatively and the bone marrow cannot produce healthy blood cells and platelets

acute

_______ leukemia is aggressive and can be fatal in a few months

chronic

_______ leukemia is less aggressive and has a better 5-year survival rate

second

______ word after acute/chronic indicates the type of cell the causes the problem in leukemia

Lymphoma

a type of blood cancer that affects the lymphatic system, which is part of the immune system. It includes two main types: Hodgkin lymphoma and non-Hodgkin lymphoma

Hodgkin lymphoma

• rarer and affects younger individuals

• more favorable survival

Non-Hodgkin lymphoma

• more common and affects older individuals more

• less favorable survivable

Multiple myeloma

• causes by plasma cells which create antibodies

• they proliferate and overwhelm the bone marrow

• reports excruciating pain since it can compromise bone health

Cell cycle

G1, S, G2, Mitosis, Cytokinesis

Interphase

G1, S, G2

G1

cell grows and synthesizes proteins for DNA replication

S

DNA is duplicated

G2

further cell growth and protein synthesis

M

cell division occurs (mitosis)

Cytokinesis

formation of 2 daughter cells

3

How many checkpoints are there during the cell cycle?

G1

The first checkpoint is at the end of ____ for DNA damage. If there is damage, DNA repair genes are activated to repair the damage. The cell cycle will stop until the DNA is fixed

G2

The second checkpoint is at the ____ phase to check if the DNA is intact and completed replication. If anything is missing or altered from duplicated DNA, tumor suppressor genes are activated for the cell to commit suicide or apoptosis

M

The third checkpoint is at the ____ phase for correct distribution of chromosomes

Genetic mutations

• can happen “by chance” during cell division

• can be caused by exposure to carcinogens (i.e., somatic mutations)

• ~90-95% of cancer cases are sporadic (i.e., caused by various carcinogens after birth)

• inherited (~5-10% of cancers by inherited genetic changes - germline mutations)

Initiation

• irreversible

• genetic mutation

• spontaneous or due to exposure to a carcinogen

Promotion

• reversible

• expansion of initiated cells

• internal and external factors promote carcinogenesis (e.g., substances in the environment, hormones, etc.)

Progression

• irreversible

• malignant growth

• genomic instability and uncontrolled growth

Carcinogenesis

The three-stage theory of __________:

1. initiation

2. promotion

3. progression

Proto-Oncogenes

• Normal role: promote cell survival or proliferation

• Impact of Mutation: unregulated cell proliferation

Tumor-Suppressor Genes

• Normal role: inhibit cell survival or proliferation

• Impact of Mutation: unregulated cell proliferation

Repair (“Caretaker”) Genes

• Normal role: repair or protect DNA

• Impact of Mutation: allow mutations to accumulate

BRCA1 and BRCA2

tumor suppressor genes involved in DNA repair. Mutations in these genes increase the risk of breast and ovarian cancers and pancreatic cancer in both men and women

BRCA1

mutations in _________ lead to a higher chance of developing ovarian cancer

TP53

is a tumor suppressor gene that regulates cell cycle and prevents tumor formation. Mutations are associated with various cancers, including breast, lung, and colon cancers. Women who have mutations in this gene have a higher risk of developing ovarian cancer.

Original 6 hallmarks of cancer cells

1. sustaining proliferative signaling

2. evading growth suppressors

3. activating invasion and metastasis

4. enabling replicative immortality

5. inducing angiogenesis

6. resisting cell death

normal cell

__________ require mitogenic growth signals to transition from a quiescent into a proliferative state

cancer cells

_________ do not require external growth factors to proliferate (i.e., they have “self-sufficiency in growth signals”)

• may have autocrine signaling capability

• over-activation of internal signaling pathways that would typically be activated by external influences

• turn off negative feedback mechanisms

• may become hyperresponsive to levels of growth factors due to receptor overexpression (e.g., EGF-R in stomach, brain, and breast cancer)

Autocrine signaling

secrete products that bind to receptors on the surface of the SAME cell that released the products, allowing for self-sufficient proliferation and growth

anti-growth signals

Cancer cells generally resist ___________

tumor suppressor genes

In cancer cells, ____________ are damaged so that tumor suppressor proteins are not effective at preventing cell division (i.e., they pass checkpoints to divide)

Invasion

Direct extension and penetration by cancer cells into adjacent tissues

invasion and metastasis

Cancer cells spread to adjacent and distant organs via ____________

Epithelial Mesenchymal Transtion

a process that allows cancer cells to gain migratory and invasive capabilities, facilitating their spread. Cancer cells go from epithelial cells to mesenchymal cells

Mesenchymal cells

have the ability to migrate through circulation to distance organs and tissues

Mesenchymal Epithelial Transition

A process that allows cancer mesenchymal cells to turn back into epithelial cells after they have found a new organ or system. This allows them to settle and proliferate in the new site.

Hayflick limit

number of replications (~40-50) before a cell commits suicide (apoptosis) or cell senescence (G0)

shorter

Replication results in _______ telomeres, which stimulate senescence

telomerase

Cancer cells express ________ to preserve telomeric length, preventing senescence or apoptosis (also known as replication immortality)

Angiogenesis

process of forming new blood vessels

low

In the presence of _______ oxygen, cancer cells can self-initiate angiogenesis to create a source for “fuel” (oxygen, nutrients, growth signals). This is BAD

VEGF

Tumor cells secrete ________ and through signaling can create its own vasculature (angiogenesis)

hypoxic

________ tumors have poor response to systemic treatment

cell death/apoptosis

Evasion of ____________ processes via:

• altering the mechanisms that monitor abnormalities

• deactivating alarm response

• impairing downstream signaling or genes involved in apoptosis

Lung

What type of cancer is most common?

Lung

What type of cancer is most common in males?

Breast

What type of cancer is most common in females?

Prostate, lung and bronchus, colon and rectum

top 3 cancers in males in the US

breast, lung and bronchus, colon and rectum

top 3 cancers in females in the US

3

1 in ____ males will be diagnosed with some type of cancer in their lifetime in the US

8

1 in ____ of males will be diagnosed with prostate cancer in the US

3

1 in ____ females will be diagnosed with some type of cancer in their lifetime in the US

8

1 in _____ of females will be diagnosed with breast cancer in the US

heart disease

What is the leading cause of death in the world?

cancer

What is the second leading cause of death in the world?

Lung, colorectum, liver

top 3 of cancer mortality in both sexes

Lung, liver, colorectum

top 3 of cancer mortality in males

Breast, lung, colorectum

top 3 of cancer mortality in females

Lung and bronchus, prostate, colon and rectum

top 3 types of cancers that contribute to new cancer deaths in males in the US

Lung and bronchus, breast, pancreas

top 3 types of cancers that contribute to new cancer deaths in females in the US

high

Localized prostate cancer has a very _______ 5-year relative survival

Cancer risk factors

• genetics

• age

• alcohol

• tobacco

• obesity

• STIs

• diet

• physical inactivity

• environmental

Group 1 (carcinogenic to humans)

Alcohol, tobacco, some types of STIs, processed meat

Group 2A (probably carcinogenic to humans)

some STIs, red meat

Group 2B (possibly carcinogenic to humans)

some STIs

Group 3

not classified as to its carcinogenicity in humans