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Biological Aspects of Lung Cancer (1), Biological Aspects of Lung…
Biological Aspects of Lung Cancer (1)
Overview of Lung Cancer
common cancer
poor prognosis
leading cause of preventable death
Types of Lung Cancer
Small Cell Lung Cancer(SCLC)
less common
exclusively in heavy smokers
poor prognosis- 7% survive 5 years
Non-Small Cell Lung Cancer(NSCLC)
composed of many types- squamous, adenocarcinoma, large cell carcinoma
Physiology of Cancer
What is cancer?
when abnormal cells grow uncontrollably
dysregulation of cell cycle
What are the two major phases of the cell cycle?
interphase-
G1(growth + copies)
S(synthesize)
G2(grows, proteins, prepares for mitosis)
Mitotic(M)- cell divides DNA into two new cells
Oncogenes vs tumor Suppressor genes
Oncogenes
- mutated versions of normal genes that promote cell proliferation, motility, and survival
What are three pathways oncogenes can be activated by?
Gene mutation- mutant protein
gene amplification- normal sequence repeated in chromosome to yield excess protein
gene translocation- movement of genetic sequence from normal position to new position to yield new fusion protein
Tumor Suppressor genes
- normal genes that inhibit cell proliferation, motility, and survival- include those that promote programmed cell death
The inactivation of what are two TSG integral to the SCLC pathogenesis?
TP53: codes for p53
integral to cell checkpoints; cell cycle arrest; apoptosis
RB1 gene: codes for retinoblastoma protein
inhibitor DNA replication; doesn't allow cell entry into S phase
What are steps in cancer cell development?
Damage to DNA
Transmission of DNA errors
Latency
Progression
Cancer progression depends on accumulation of cancer hallmarks
newly formed biological characteristics
associated with number and types of mutations accumulated by a cell
What are the 6 classical hallmarks of cancer
growth factor of independence
What are growth factors?
groups of cytokines and hormones
What are three mechanisms cancer cells use to achieve self sufficiency?
Make growth factors stimulate their own and neighboring receptors
Alter number, structure, or function of receptor; make more likely to relay a growth signal
deregulate downstream signaling pathways to permanently turn on growth
insensitivity to anti-growth signals
counteracts positively acting signals- promote them into not growing- G0; regulates cell cycle progression through regulatory proteins coded by
tumor suppressor genes
;
How does cancer inhibit anti-growth signaling pathways?
reduced receptor number
enable mutations to tumors suppressor genes- like
gene deletion
activating invasion and metastatis
metastatis is spread of cancerous cells
What is the prosses of spreading?
detachment of tissue
enzymic digestion of surrouding tissue
migration to and penetration of lymphatic vessels
survival in circulation till location reached
attachment to blood vessel wall and extravasion of blood
proliferation and invasion in new location
cancer cells can turn from epithelial to mesenchymal cells- differentiated cells to dynamic cell
enabling replicative immortality
Normal cells undergo replicative senescence- cells cannot fully replicate telomeres
cancer cells maintain length of telomeres
angiogenesis
growth of blood vessels controlled by pro-angiogenic and anti-angiogenic signals
cancer promotes pro-angiogenic proteins so it can progress
resisting cell death
cancer cells evade apoptosis by
extrinsic pathway- ignoring death signals sent through immune system
intrinsic pathway- reset balance of intracellular survival molecules in mitochondria
What are the new hallmarks of cancer?
Reprogrammed Energy Metabolism
cancer has preferential use of glycolysis with generation of lactate
provides important things for growth
Evasion of immune destruction
evade immune system
main ways of treating cancer are activating inhibitors, ect.
Biological Aspects of Lung Cancer(2)
Types of Cancer
Carcinoma
from epithelial cells
skin or tissue that lines organs
Sarcoma
connective tissue
Leukemia
stem cells of bone marrow
Lymphoma
lymphatic system
Gilomas
nervous tissue
Anatomy of the Lung
Respiratory system: enable breathing and gas exchange
Billateral, asymmetrical structure
Right Lung - 3 lobes
left lung- 2 lobes and cardiac notch
house conduits for air and serve as site for gas exchange
special epithelial tissue (tissue lining)
What are the components of the functional anatomy of the lungs?
Conducting Zone
conduits to gas exchange sites
includes upper and lower respitary tract
trachea, bronchi, terminal branchiotes
respiratory zone
site of gas exchange
microscopic structures
Respiratory Muscles
diaphragm and other muscles that assist breathiing
Origins of SCLC and NSCLC
Small Cell & Large Cell carcinoma- neuroendocrine
NS- Sqamous cell carcinoma- basal cell
Adenocarcinoma- NS- Type II Alveolar cell
SCLC Details
15% of all lung cancers
early metastasis and poor prognosis -> late stage diagnosis
greatest risk factor is cigarette smoking; aligns with molecular signature of smokers; contributions from other genetic factors
Disease presentation and staging
How is lung cancer presented?
Respiratory symptoms- coughing, dyspnea, hemoptysis
Lung mass in radiological findings;
How is lung cancer staged?
Tumor Biopsies
Tumor-node-metastasis(TNM) classification system reflects disease progression
analysis of
anatomic discrimination, lymph node involvement, and distant spread
What are the stages of Lung cancer defined by?
Stage 1:
Restricted to one side
less than T1A or greater than 3cm
no lymph node involvement
Stage 2:
Restricted one side
5-7cm lymph node
Stage 3:
cancer spread beyond lymph nodes to both sides of chest
Stage 4:
cancer accompanied by pleural effusion or metastasis; fluid build up in lungs; distant lesions in brain, bone, or liver
How is SCLC managed?
Earl stage disease: surgery or radiotherapy- cisplatin-etoposide
locally advanced disease: chemoradiotherapy - prophylactic cranial irradiation PCI
Extensive metastatic disease: ChemoIO- immunotherapy & consolidative thoracic radiotherapy