Unit 2 Pathophysiology - Chapter 12 Cancer Biology Flashcards
Benign tumors
- encapsulated
- contain differentiated cells
- organized stroma
- do not spread
Malignant tumor
- rapid growth
- anaplasia (loss of maturity + functions)
- loss of differentiation
- no cell organization
- no capsule
- invade blood vessels + lymphatics + distant metastases
Carcinomas and leukemias arise from?
Epithelial tissues // leukemias
CIS or carcinoma in situ
preinvasive epithelial tumors of glandular or squamous cell origin
early stage cancers localized to epithelium and did not penetrate local basement membrane (right under epithelium) and did not invade surrounding stroma
Genetic changes - cancer
small, large DNA mutations in genes, chromosomes, non-coding RNAs, altered chemical modifications of DNA + histones (epigenetics)
Chromosome translocation
partial or whole chromosome breaks off and attaches to another
gene amplification
Increase in number of genes; maybe also more RNA and protein production from gene
DNA methylation
methylation of the DNA sequence of a gene may turn the gene off so it does not make a protein.
histone acetylation
By modifying chromatin proteins and transcription-related factors, these acetylases are believed to regulate the transcription of many genes.
altered expression of non–coding RNA
chromatin remodeling, regulate gene expression at transcriptional or post-transcriptional
Driver mutations
drive progress of cancer
Passenger mutations
random events; along for the ride hehe
Cancer cell can develop own mutations?
Yes, resulting in genomic heterogenous mixture of cancer cells w/ subsets that accumulate more mutations => increase malignant potential
Development of cancer analogus to what?
Wound healing
initial proliferation of cancer cells and enlarging tumor => creates proinflammatory mediators by cancer cells + adjacent nonmalignant cells
These mediators => recruit inflammatory/immune/tissue repair cells forming the stroma (connective, functionally supportive framework of a biological cell, tissue, or organ) that surround and infiltrate tumor
Stromal and cancer cells relation
D/t extensive paracine signaling amongst both populations
- increased proliferation and heterogenous growth during tumor growth
- stromal cell phenotypes that promote more cancer progressio nand metastatic potential
Hallmarks/enablers of genomic alterations for cancer
- sustained proliferative signaling
- evade growth suppression
- genomic instability
- replicative immortality
Hallmark secondary to genomic change
cellular adaptations, including angiogenesis (formation of new blood vessels) and reprogramming energy metabolism
Hallmark/enablers - protective mechanisms
apoptotic cell death, promote tumor inflammation, avoid immune destruction
last hall mark - most important?
culmination of all previously mentioned: activating invasion and metastasis
Cancercous cells express specifically what?
mutated or overexpressed proto-oncogenes (oncogenes), they are independent of normal regulators and signal uncontrolled proliferation
RAS oncogene
result from point mutation, all Ras proteins are GTPases which act as molecular switches in the cell, regulating signaling pathways and other interactions until they mutate and for cancer
Philadelphia chromosome in CML or chronic myeloid leukemia
Comes about d/t translocation that creates novels protein fusion of BCR + ABL genes and expression for unregulator promotor of cell growth
Abl is tumor suppressor gene
BCR protein may act as a GTPase activating protein (GAP). GAPs turn off (inactivate) proteins called GTPases, which play an important role in chemical signaling within cells.
How do Tumor suppression genes work in cancer
mutations of each allele, for each parent in terms of inactivating said gene
Common mutation in cancer cells
inactivation of tumor suppressor gene, tumor protein P53 (TP53) important in contrlling gene expression for DNA damage repair, suppression of cellular proliferation during genomic repair, and apoptosis initiation => resulting mutation rates and cancer
inheritable tumor-suppressor gene
TP53, retinoblastoma gene (RB) [nuclear protein that acts as a cell cycle control checkpoint at the G1 phase], or breast cancer genes [BRCA1 and BRCA2]
Caretaker genes
susceptible to disruption from inherited mutations; caretaker genes responsible for maintaining genomic integrity
Abnormal gene silencing
major factor in cancer; passed down from parent => child => single => progeny d/t epigenetic silencing
Are cancer cells immortal?
Yes, when they reach critical age, cancer cells activate telomerase to restore and maintaine their telomeres, allowing to divide repeatedly
How to fully rid of cancer in a body?
Target cancer stem cell
What’s essential for tumor growth?
Access to vascular system
VEGF or vascular endothelial growth factor
stimulate new blood vessel growth or angiogenesis when stromal or cancer cells excrete this factor
Cancer cell division requirements?
Can often occur in hypoxic and acidic environment; cancer genes also encourage aerobic glycolysis and high gluce utilization
defects in intrinsic or extinsic pathways
provide resistance to apoptotic cell death
Increased BCL-2
blocks apoptosis in most follicular B-cell lymphomas
family proteins are the regulators of apoptosis, but also have other functions. This family of interacting partners includes inhibitors and inducers of cell death.
Chronic inflammation
can l/t increased risk of cancer; e.g gastric cancer and infection w/ Helicobacter pylori
Tumor-associated macrophage (TAM)
usually M1 or classic proinflammatory macropahge is the primary one in acute inflammatory response
While M2 macrophage creates during healing:
* antiinflammatory mediators to suppress inflammation
* induce cellular proliferation
* angiogenesis
* wound healing
TAM mimics M2
Cancer-associated fibroblasts (CAFs)
synthesize extracellular matrix that surrounds and permeates tumor; contribute to spread + metastasis
Viruses + cancer
Viruses associated w/ 15% of all human cancers. Cervix and hepatocellular carcinoma account for 80% of virus-linked cancer cases
Human papillomavirus (HPV) anad hepatitis B virus (HBV)
These vaccines against oncogenic viruses are expected to protect against initial infection and develop of cervical + liver tumors respectively
T cells and NK cells for cancer
They can recognize unique antigens + markers on tumors cells l/t destruction
How do cancer cells avoid immune system?
- Produce immunosuppressive factors
- Immunosuppresive T-regular cells
- Evolviing tumor-antigen negative variants
- suppression of antigen-presenting MHC class 1 molecules
Metastasis
Requires cells to have many new abilities
* invade
* survive
* proliferate in new environment
Traits for Invasion in cancer
- loss of cell-to-cell contact
- degrade ECM
- migration of tumor cells to vascular or lymphatic systems
- Stromal cells are important (TAMs or tumor associated macrophage)
Epithelial-
mesenchymal transition
Carcinomas undergo this process where many epithealial-like characteristics are lost (such as polarity, adhesion to basement membrane), resulting in:
* increased migratory movement
* increased apoptosis resistance
* dedifferentiated stem cell-like state that favors foreign (lose specialized characters) microenvironments
* create metastasis
Cancers move purposely?
Can move to specific sites d/t particular receptor expression for ligands expressed by cells
Paraneoplastic syndromes
rare symptom complexes d/t biologically active substanes released from tumor or by an immune response triggered by tumor; manifest sx not directly caused by local effects of cancer
Clinical manifestations of cancer
pain, cachexia (wasting, weakness of body), anemia, leukopenia, thrombocytopenia, and infection
Pain
late stage of cancer; pressure, obstruction, invasion of structure sensitive to pain, stretching, tissue destruction, inflammation
Fatigue
most frequently reported sx of cancer and cancer tx
Cachexia
multiorgan syndrome
* anorexia
* muscle wasting (involves many protein signal pathways and inflammatory mediators)
* thermogenesis
* altered heart + liver fx
* gut malabsorption
* early satiety/taste alterations
* altered metabolism (protein, lipid, carbohydrate)
Anemia w/ cancer
d/t malnutrition, chronic bleeding, resultant iron deficiency, chemotherapy, radiation, and malignancy in blood forming organs
Leukopenia
d/t chemothrapy (toxic to bone marrow) or radiation (kills circulating leukocytes
Thromobocytopenia d/t cancer
chemotherapy or bone marrow malignancy
Infection and cancer
Leukopenia, immunosuppresion, or debility
GI tract + cancer
d/t chemotherapy and radiation => malabsorption, oral ulcers (stomatitis), diarrhea
Alopecia and skin d/t cancer
hair loss d/t chemotherapy on hair follicles
while for skin, decreased renewal rates => l/t skin breakdown and dryness
Examination of tumor tissue by pathologist
Diagnosis of cancer, uses variety of tests
Tumor staging
T (tumor spread), N (node involvement), and M (metastasis) system
cancer classification methods
immunohistochemical analysis for protein express + molecular analysis of tumors
Tumor markers
found in cancer cells, blood, spinal fluid, or urine; includes hormones, enzymes, genes, antigens, antibodies => help diagnose and follow course of cancer
Cancer therapy
surgery, radiation therapy, and chemotherapy, or combination w/ limitations
Surgical therapy
for nonmetastatic disease and a palliative measure to alleviate symptoms
Radiation therapy
ionizing radiation cause cell damage; goal is to damage tumor w/o excessive toxicity or damage to other structures
Chemotherapy
vulnerability of tumor cells in various stages of cell cycle; current tx uses combinations of drugs with different targets and toxicities
Immunotherapy
modify immune system into destructive condition
