L34: Neoplasia II Flashcards
True or False: Cancer is the second leading cause of death in males and females
True
True or False: Chronic inflammatory disease of the GI (UC, pancreatitis, hepatitis, H. pylori) can increase cancer risk
True
Mechanisms
- ROS cause genomic damage
- Increased stem cell pool
- Compensatory proliferation
- Maladative immune response
What are the 7 mechanisms that form molecular basis of cancer?
- Defects in DNA repair
- Self-sufficiency in growth signals
- Insensitivity to growth inhibition (loss of TS genes)
- Evasion of apoptosis
- Limitless replication potential
- Sustained angiogenesis
- Ability to invade and met
Which condition is associated with increased chance of UV-induced skin cancer due to defects in nucleotide excision repair pathway?
Xeroderma Pigmentosum
Activation of ____ allows for self-sufficiency in growth signals in cancer
Oncogenes (proto-oncogenes that have been mutated)
True or False: Increased growth factor production is NOT enough to cause neoplastic transformation
True
True or False: EGF/ERBB2 (HER2) is amplified in 25% breast cancers
True
Which oncogene is the most common abnormality of proto-oncogenes?
A. RAS
B. HER-2
A. RAS
Melanomas, colon/lung/pancreatic/kidney/bladder tumors involve which proto-oncogene?
A. Cyclin D
B. MYC
C. RAS/RAF
C. RAS/RAF
Burkitt Lymphoma, small cell lung carcinoma, and neuroblastoma are associated with which proto-oncogene?
A. Cyclin D
B. MYC
C. RAS/RAF
C. RAS/RAF
____: A gene that, when mutated, causes a decrease or LOF
TS Gene
What does Knudson’s 2 Hit Hypothesis of Oncogenesis state?
1) Need to lose both functional alleles of a TS gene
2) Loss of a single allele of a TS - “Haploinsufficiency”
True or False: There is a sporatic and familial form of Rb
True
___, the most common TS gene and most common target for genetic alterations in tumors
p53
Mutated p53 has ___ activity over WT p53 (does not need to lose both alleles - one is enough)
A. recessive
B. dominant
B. dominant
If a mutation is inherited with p53 mutation, what is the condition known as? In this case, p53 has dominant activity over WT, meaning?
Li-Fraumeni Syndrome
- do not need to lose both alleles – one is enough
True or False: p53 can lead to G1 arrest, DNA repair, and apoptosis
True
Which apoptotic pathway is mediated by death receptor? Which is mediated by stress, radiation, and chemicals?
Extrinsic: death receptor
Intrinsic: stress, radiation, and chemical mediated
ok
Cancer cells increased levels of the enzyme ___, which prevents telomere shortening, leading to “limitless” replicative potential
telomerase
All tumors consists of which two components?
- Parenchyma - clonal neoplasic cells
- Stroma - CT, B. vessels, macrophages, lymphocytes
True or False: Cancer cells can stimulate neoangiogenesis (new vessels sprout from existing capillaries) and vasculogenesis (endothelial cells from b. marrow)
True
What does angiogenesis provide cancer cells?
- Nutrients and endothelial cells secrete GF
- Access to vasculature
____ are enzymes made by cancer calls that promote angiogenesis. Results in remodeling of ECM
_____ results in increased production of pro-angiogenic GF’s (FGF and VEGF)
Protease; Hypoxia
In cancer, cytokines increase endothelial growth and attract new ___ towards the tumor
vessels
How does cancer invade and metastasize?
- Invades ECM
- Vascular dissemination, homing, colonization
Steps by which invasion/met occur?
- Tumor cells detach from each other due to decreased E-Cadherin
- Enzymes secrete from tumor and stromal cells degrade BM
- Binding of tumor cells to proteolytically generated binding sites
- Tumor cell migration
What is the first hit and second hit in evolution of colorectal cancers (adenoma-carcinoma sequence)?
First - germline or somatic mutation of cancer TS genes
Second - methylation abnormalities
ok
What are two examples of inherited predispositions to cancer?
- Autosomal dominant inherited cancer syndromes
- point mutation is a TS - Autosomal recessive
- defects in DNA repair leads to DNA instability
CA-125 is a tumor marker for ___ cancer while MYCN is a tumor marker for ___ cancaer
ovarian; neuroblastoma
True or False: PSA and CA-125 are biomarkers found in the blood while HER-2 and ER are biomarkers found in the tumor itself
True
BRAF V600E activating mutations are found in melanoma patients. Which drug type is best for treating these patients?
BRAF Inhibitors
Which two biomarkers can be used to stage the disease?
A. MYCN
B. Neuroblastoma
C. PSA
D. BRCA1/2
A. MYCN/ B. Neuroblastoma
True or False: Bcr-Abl and CML are biomarkers that can be used to dx
True
