Cancer

Uncontrolled cellular proliferation

• Damage (mutations) in DNA
• -errors during replication and mitosis
• -carcinogens (substances that can cause cancer)
• Viruses
• -play a role in ~15% of cancers
• -like hpv, hepatitis

Continue to divide even if they are tightly packed together

B) they have escaped normal cell cycle controls

• A mass of cells
• Can be benign or malignant

Confined locally (does not spread), easier to remove

Invades surrounding tissue, spreads to other parts of the body, often come back

Spread of cancer cells

Malignant tumor

Number varies depending on which genes are mutated

• You are acquiring mutations through out your life
• The immune system gets weaker as you age

• Oncogenes
• Tumor Suppressors

Gene that when mutated (it turns into an oncogenes) or overexpressed can contribute to turning a normal cell into a cancer cell

• Growth factors
• RTKs 
• GTPases
• Transcription factors

• Mutation which changes protein structure
• -increases activity or cause loss of regulation
• Increase in protein concentration
• -increase in expression, stability or gene duplication
• Chromosomal transloaction
• -constitutively expressed fusion protein or expression in wrong cell or at wrong time

• E) gene suppression
• -oncogene is the "gas" so gene suppression wouldn't cause it to continuously run

• Genes which have repressive effect on the regulation of the cell cycle or promote apoptosis (cell death)
• Usually follow the "two-hit hypothesis"
• -both copies (from mom and dad) of the gene must be non-functional (now you have no "breaks" to stop the cell growth)

• "the Guardian of the Genome"
• Tumor Suppressor
• Regulates the cell cycle
• Mutated in ~50% of human cancers
• Inherited mutations = Li Fraumeni syndrome

• Uncontrolled proliferation (self-sufficient)
• Evasion of growth suppressors (inactivation of tumor suppressors)
• Resistance to apoptosis
• Develop replicative immortality (activate telomerase)
• Induce angiogenesis
• Invasion and metastasis (they can travel through the body and start growing there)
• Changed energy metabolism (anaerobic)
• Immune system evasion
• Genomic instability
• Inflammation

• Went to Johns Hopkins in Jan 1951 and was diagnosed with cervical cancer
• Admitted in August for treatment

• Polio vaccine, cancer, AIDS, gravity, radiation
• 20 tons of cells have been used
• 11,000 patients
• Over 60,000 papers

Genetic changes alter the function of the cancer cell's protein products

• Resection
• Chemotherapy
• Radiation
• Bone Marrow Transplants

Surgical removal of a tumor

• It goes after rapidly dividing cells
• -Side effects come from it attacking normal rapidly dividing cells

It could increase the chance of getting cancer in a different area

Use healthy bone marrow to make white blood cells (helps pediatric Lukemia)

• Target specific pathways/proteins involved in tumor development
• Angiogenesis inhibitors- prevent new blood cell formation

• General boost to the immune system (help immune system recognize cancer cells)
• Attack specific targets
• Deliver chemo to cancer cells

Using a viral vector to deliver a functional gene

• Hepatitis B and HPV (prevent the cancer)
• Prostate (treat the cancer)

• Skin cancer
• More than 3 million cases diagnosed per year
• 1 in 5 people will develop it
• Most commonly caused by UV radiation

• Melanoma
• Worst 5 year survival rate
• One of most common in young women

• That your DNA is already damaged
• Melanin is released because it's your body's natural sunscreen

• There is a physical barrier that reflect UV rays
• Regular spray/cream helps the skin absorb uv rays

• Asymmetry- when half of the mole does not match the other half
• When the border (edges) of the mole are ragged or irregular
• When the color of the mole varies throughout 
• If the mole's diameter is larger than a pencil eraser

• Breast cancer
• 1 in 8 women will develop invasive breast cancer

• 89%
• If found in stage 0 or 1 = almost 100%
• Stage 2= 93%
• Stage 3=72%
• Stage 4 (metastatic)= 22%
• Early detection is key 

• Known risk factors include: Smoking, obesity, alcohol, exposure to carcinogens, increased estrogen exposure
• Only 5-10% linked to inherited gene mutations (BRCA 1 & BRCA 2 are tumor suppressors)
• -Mutation in one copy of BRCA 1= 60% chance of developing breast cancer before age 50 compared to 2% chance if both copies are normal

• ~222,000 new cases each yeaar
• ~155,800 deaths (26% of all cancer deaths because it's not caught until its too late)
• Overall 5 year survival rate is 18%

• Smoking
• 70 confirmed carcinogens

• Asbestos
• Radon gas
• Pollution
• Exposure to carcinogens
• -coal dust, gasoline, mustard gas
• Radiation therapy to the lungs

Pap smear testing

• HPV (human papilloma viruses)
• At least 50% of sexually active people will get it at some point
• Most strains only cause warts and the body can clear the infection on its own
• High risk types of HPV linked to cancers of the cervix, vulva, vagina, penis, anus and mouth

2 strains of HPV 16 and 18

• When HPV is not present: During the G2 checkpoint, a functional p53 protein detects a DNA mutation
• Cervix cells with mutated DNA do not divide
• Cervix remains healthy
• When HPV is present:
• p53 protein is deactivated by the p53 inhibitor
• With p53 deactivated, cervix cells with mutated DNA successfully divide
• Mutated cervix cells grow uncontrollably into a tumor