Cancer I APP LS

Question 1

Characteristics of Benign tumors

Answer 1

• Well differentiated cells with preserved specialized features of the parent cells (e.g. hormone release)
• Well demarcated, often encapsulated masses; no invasion of surrounding tissues
• No distant metastases

Question 2

Characteristics of Malignant Tumors

Answer 2

• Lack of differentiation
• Locally invasive, infiltrating surrounding tissues
• Frequently present distant metastases

Question 3

Cancer specific therapies:

Answer 3

o Hormone therapies (anti-estrogen for breast cancer, anti-androgen for prostate cancer)

o Inhibitors of cell signaling molecules (tyrosine kinase inhibitors, mTor inhibitors)

o Anti-angiogenic therapies (VEGF targeting)

o Immune therapies (therapeutic and preventive cancer vaccines, antibodies, cytokine treatment, cell transfer therapies)

o Gene therapy (modification of the immune response, replacement of mutated/missing tumor suppressor, knockdown of oncogenes, suicide gene therapy)

Question 4

Problems with conventional cancer treatments:

Answer 4

• high toxicity - resistance is common - frequent tumor relapses current research focuses on development of more specific cancer therapies.

Question 5

cancer stem cells

Answer 5

• 2nd model of tumor progression, clones of cancer cell comes from these stem cells with protential to proliferate and differentiate.
• often not sensitive to radio- and chemotherapy.

Question 6

tailored therapy designed based on ___ for the particular patients seems to be a promising new therapeutic approach.

Answer 6

specific cancer phenotype

Question 7

Cancer diagnostic: 6 – IBBMMG

Answer 7

o Imaging (X-ray, ultrasonography, CT)

o Biopsy (histopathological analysis)

o Biochemical assays detecting tumor-specific markers, enzymes and hormones (PSA – prostate cancer, CEA – GI tumors)

o Molecular diagnosis – detection of characteristic chromosomal aberrations (Fluorescent In Situ Hybridization - FISH) or tumor-specific proteins (PCR)

o Molecular profiling – characterization of tumors facilitating their stratification or tailoring tumor therapy

o Genetic screening – identification of high risk population (screening for BRCA mutations)

Question 8

Long term effects of current cancer therapies:

Answer 8

o Infertility o Secondary cancers o Osteoporosis o Growth abnormalities

Question 9

Both radio- and chemotherapy target proliferating cells, including normal cells, and therefore cause these side effects:

Answer 9

o Hair loss o GI dysfunction o Skin reaction o Bone marrow damage – depletion of immune cells and erythrocytes

Question 10

Conventional, non-specific cancer therapy:

Answer 10

o Surgery (local) o Radiotherapy (local) o Chemotherapy (systemic treatment – targets metastases and residual disease)

Question 11

Examples of specific cancer symptoms:

Answer 11

o Persistent cough – lung cancer o Long-term constipation, diarrhea, blood in stool – colon cancer o Sweating, heart palpitations, hypertension – pcheochromocytoma

Question 12

Non-specific cancer symptoms:

Answer 12

o Unexplained weight loss o Fever o Fatigue o Pain o Skin changes

Question 13

Cancer Symptoms:

Answer 13

• may cause almost any sign or symptom. - symptoms depend on type of cancer, its localization, and its effect on nearby organs or tissues (local invasion, pressure). - If a cancer has spread, symptoms may appear in different parts of the body.

Question 14

Models of tumor progression:

Answer 14

Clonal evolution vs. Cancer stem cells

Question 15

Features of malignant cancer cells:

Answer 15

• Self sufficiency in growth signals (don’t need signal for growth) - Insensitivity to growth-inhibitory signals - Evasion of apoptosis - Limitless replicative potential - Sustained angiogenesis - Ability to invade and metastasize - Evasion of host immune response

Question 16

The probability of developing cancer depends on __

Answer 16

• individual susceptibility (e.g. germline mutations in tumor suppressor genes) - environmental factors

Question 17

Cancer II: Tumor progression and treatment Objectives: 1) Define angiogenesis and its role in tumor progression 2) Describe mechanism of metastases 3) Explain interactions between cancer cells and immune system 4) Describe models of tumor progression and evolution 5) Describe the clinical manifestations of cancer and its diagnosis 6) Compare cancer treatment modalities and their side effects

Answer 17

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Question 18

Tumor suppressor genes - what do they encode? - relationship to cancer

Answer 18

• encode proteins, which in normal cells inhibit proliferation and/or stimulate cell death (apoptosis). - These genes are often inactivated in cancer cells, which leads to uncontrolled cell growth, accumulation and propagation of defective cells, which are normally eliminated via apoptosis.

Question 19

ABL

Answer 19

• tyrosine kinase, which promotes apoptosis - In chronic myeloid leukemia, ABL gene is translocated from chromosome 9 to 22 and fuses with part of the breakpoint cluster region (BCR) gene. - This chromosome 22 ends up looking very small and is named chromosome Philadelphia. - Normally ABL protein goes to the nucleus and stimulates apoptosis - but when ABL and BCR genes are fused the resulting gene product, BCR-ABL fusion protein stays in the cytoplasm and starts to phosphorylate and activate RAS-RAF cascade.

Question 20

Tumor suppressor genes can be inactivated via:

Answer 20

o Point mutations o Deletions o Chromosomal aberrations o Epigenetic modifications

Question 21

Cancer stem cells

Answer 21

– new theory indicating that tumor growth can be driven by small population of cells with self-renewal capacity and high tumorigenic potency called cancer initiating or cancer stem cells (CSCs). – These cells are more resistant to chemo and radiotherapy, and environmental factors. They sustain tumor growth and are responsible for its relapse after treatment.

Question 22

Clonal evolution of tumor progression:

Answer 22

– tumor cells continously mutate in order to adapt/evolve, become malignant and evade treatment (progressive accumilation of mutations)

– genomic instability allows the new clones to acquire new, more malignant features when under environmental stress (hypoxia, chemotherapy).

Question 23

Examples of overexpression of growth factor receptors:

Answer 23

a) ERBB1 in squamous cell carcinomas of the lung
b) ERBB2 (HER2) in breast cancer – HER2 receptor is not expressed in normal cells, therefore, if HER2 receptors are present can treat pt with HER2 antibodies (only given to HER2+ patients).

Question 24

Explain: overexpression of autocrine growth factors.

2 examples.

Answer 24

when a cell starts producing its own growth factors:

o Platelet-derived growth factor (PDGF) in glioblastomas

o Transforming growth factor α (TGF-α) in sarcomas

Question 25

What growth factor receptor is mutated in glioblastoma? What changes with the receptor?

Answer 25

Epidermal growth factor receptor (EGFR) ERBB1 is truncated in glioblastoma

o these receptors have an extracellular part that binds to GF and an intracellular part that activates signal cascade.

o If mutation changes extracellular part of receptor, it can’t be bound/controlled by GF. 2 things can happen in this case:

o either the mutated receptor is rendered useless and inactive

o or it can be constitutively active due to loss of regulation

Question 26

Normal functions of RAS

Answer 26

• When the receptor is inactive, RAS is bound to GDP
• When GF binds to receptor, RAS releases the GDP to bind GTP (active form) and starts phosphorylation of other proteins
• GTP is hydrolyzed to GDP and RAS in inactivated again

Question 27

What happens if RAS is mutated? (2 possible) What cancers is it associated with?

Answer 27

• Point mutations in codons 12/13 = can’t release GTP
• Point mutation in codon 61 = can’t hydrolyze GTP
• TOO MUCH RAS ACTIVATION = constitutive activation of RAF-MAPK cascade
• associated with pancreatic and colon cancer.

Question 28

RAS and ABL are ___ proteins

Answer 28

Signal-transducing proteins

Question 29

Oncogene Activation may result from: (4)

Answer 29

o Point mutations o Chromosomal translocations o Gene amplification o Over-expression due to changes in regulatory elements

Question 30

Mutations of oncogenes are usually __

Answer 30

dominant (mutation in one allele is sufficient to cause changes in cell phenotype)

Question 31

Proto-oncogenes encode: (4)

Answer 31

o Growth factors (platelet-derived growth factor PDGF, transforming growth factor-α TGF-α)

o Growth factor receptors (HER-2, epidermal growth factor receptor EGFR)

o Signal transduction molecules (Ras, Src)

o Transcription factors (Myc)

Question 32

human cancers associated with viral infections (4) :

Answer 32

o Burkitt’s lymphoma - Epstein-Barr virus

o Cervical cancer – Human papilloma virus (HPV)

o Liver cancer – Hepatitis B virus (HBV)

o T-cell leukemia – Human T-cell leukemia virus 1 (HTLV-1)

Question 33

Viruses can also contribute to cancer development by …..

Answer 33

interfering with molecules that control internal cell proliferation

Question 34

Process of neoplastic transformation is often associated with mutations of proto-oncogenes converting them to …

Answer 34

• constitutively active oncogenes
• overexpressed proto-oncogenes