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Introduction to Cancer

Presentation for Stanley Middle School

Jennifer Lu

on 28 May 2013

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Transcript of Introduction to Cancer

CANCER Big Questions What is cancer?

What causes cancer?

What treatments are there for cancer? What is cancer? What causes cancer? How do we
treat cancer? Disease of multicellular organisms

Expansion of mutant clone


Cancer Cancer arises from a Darwinian process of variation and selection Cancer Classification Tumors are classified by tissue of origin Dr. Ping Van Pell and Jennifer Lu, Cellerant Therapeutics Types of Tumors Tumor = localized excess of cell proliferation (a lump) Benign Malignant Grow fast
Remain localized
Not usually lethal Grow slowly
Spread throughout body
Typically lethal Carcinoma = epithelial cells (lung, breast, etc.)
Sarcoma = connective tissues (adipocytes, fibroblasts, etc.)
Hematopoietic malignancy = immune system, blood forming tissues (B-cells, T-cells, etc.)
Neuroectodermal tumors = nervous system (neurons)
Leukemia = circulating cells (white blood cells, red blood cells, etc.) It's complicated! But how do we know when something is considered a "cancer"? FYI, this is not the right cancer... The Hallmarks of Cancer (2000) Normal cells require specific signals for growth and proliferation
Mutations in cancer cells often short-circuit these pathways and allow activation without extracellular stimulus Antigrowth signals can cause cells to "hibernate" in a quiescent state (Go)
Cancer cells become insensitve to antigrowth signals because of mutations in pathways that mediate those signals Apoptosis = programmed cell death or "cell suicide"
If the cell has acquired a mutation that inactivates the apoptotic pathway, this will result in excess cell proliferation Normal somatic cells: 60-70 doublings
Chromosome ends (telomeres) shorten after each divison, and eventually the ends become "unprotective" and result in cell death
Telomerase is an enzyme that maintains the length of telomeres - no limit to number of doublings
Many cancer cells upregulate expression of telomerase and can proliferate indefinitely All cells require nutrients and oxygen - need to be close to a blood vessel
Lack of blood vessels would limit size of tumor
Tumors are able to secrete factors that stimulate the growth of new blood vessels Cancer cells can penetrate into adjacent tissues by invasion and metastasis
Invasion = breaking through the membrane that normally restrains cells
Metastasis = spread to distant sites in the body, ability to survive and grow in a foreign tissue Not eating your vegetables!

Watching too much TV!

Not doing your homework!

Spending too much time on your phone! Genetics vs. Environment External Causes Genetic Changes Results chemical carcinogens


viruses point mutations

chromosomal changes

epigenetic changes inactivation of genes that suppress cancer - tumor suppressors

activation of genes that induce cancer - oncogenes Genetics Environment Point mutations - single nucleotide substitution in DNA P53 (cell cycle regulator) - present in ~50% of human cancers
BRCA1/2 (DNA repair) - increased risk for breast and ovarian cancer
Rb (cell cycle regulator) - increased risk for retinoblastoma Chromosomal changes Aneuploidy - alteration in chromosome number
Translocation - exchange between non-homologous chromosomes
Amplification - tandem duplication of large segments
Deletions - segments deleted with chromosomes Because each cell can obtain the 6 hallmarks of cancer by different means, one type of cancer can be VERY different from another type Chemical Carcinogens Benzo[a]pyrene - tobacco smoke and coal tar - enzymes in your cells convert BaP to DNA adduct that can cause mutations (lung and other cancers)

Heterocyclic amines (HCA) - produced when meats are cooked at high temperatures (frying, grilling) - again converted to DNA adduct (colon cancer) Radiation X-rays - induce reactive oxygen species in cells that can cause single/double strand breaks and mutations

UV - induces formation of dimers in DNA Aflatoxin B1 - molds grown on rotten peanuts and grains - also converted by enzymes to DNA adduct (liver cancer) And to top it off... The DNA replication process is subjected to a low but significant level of error

The nucleotides in DNA undergo spontaneous chemical changes, leading to base alterations Never Fear! Mechanisms to fix errors in DNA replication Proof-reading enzymes - removes wrong nucleotide and tries again
Mismatch repair enzymes - monitors for miscopied DNA sequences, very sensitive to loops in DNA caused by mistakes Physical barrier: melanin-producing cells to block UV
Enzymes and other molecules to inactivate carcinogen
Vitamin C and E for reactive oxygen species
Glutathione-S-transferases for detoxifying certain carcinogens Cellular defenses against carcinogens Cancer Diagnosis/Screening Clinical Diagnosis Blood Tests Imaging Technology Biopsy Patient notices lump or lesion
Symptoms suggestive of specific cancers
General ill-health Anemia has been associated with chronic conditions such as cancer
Several cancer biomarkers can be found in the blood X-ray, MRI, PET - use different waves to obtain images of internal organs or cells Gather cells from tissues to detect malignant cells by morphology Now that you know more about cancer...
If you were designing a cancer therapy, what would you target?
How would you target it? Current Cancer Therapies Target: Proliferating Cells,
Damaged DNA Repair Cancer cells are actively dividing - unlike most of your cells Surgery Oldest treatment of cancer, with many recent improvements and minimal damage to surrounding tissue Plays a role in prevention, diagnosis, and treatment
Removal of polyps in colon to prevent colorectal cancer
Obtain material for analysis to make a precise diagnosis and plan a treatment strategy
Cytoreductive surgery - reduce tumor mass
Palliation - relief of pain, obstruction
Reconstruction - restoration of function, cosmetic Cancer cells have "lost" their DNA repair abilities Radiation Therapy
Photons (x-rays, UV) or particles (protons, electrons)
Induces single- and double-stranded breaks, cell death Chemotherapy
Drugs that target cells which are dividing rapidly
Side Effects: bone marrow depression, nausea, hair loss, etc. The entire hematopoietic system can be abated with a very high dose of chemotherapy or irradiation Bone Marrow Transplantation It is possible to "rescue" this defect by injecting bone marrow or BM stem cells from another individual - these cells will generate all the cells of the hematopoietic system This treatment is used to treat lymphomas and leukemias where the disease is not localized - donor BM-derived immune system attacks and kills any residual lymphoma/leukemia and keeps it in check Block off one of the required abilities for cancer
ignore anti-growth
produce own growth signals
replicate indefinitely Can use an antibody or a small molecule Examples: Herceptin for breast cancer
Avastin against angiogenesis Target: One of the 6 Hallmarks of Cancer make blood vessels
evade apoptosis
invade other tissues Cancer comes from changes in your DNA! LEUKEMIA! 90-95% of cancer cases attributed to environment
5-10% attributed to genetics
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