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What is the definition of neoplasia?
New growth
What is a tumor?
A collection of cells and stroma
What is oncology?
The study of tumors
How are benign tumors named?
Tissue name + "-oma"
What is a chondroma?
A benign cartilaginous tumor
What is an adenoma?
A benign tumor of glandular structures
What is a polyp?
A benign grossly visible projection above a mucosal surface
What is a sarcoma?
A malignant tumor of mesenchymal tissues
What is a carcinoma?
A malignant tumor of epithelial cells
What is a melanoma?
A malignant tumor of melanocytes
What is the estimated percentage of lung and bronchus cancer incidence in men?
13%
What is the estimated percentage of lung and bronchus cancer incidence in women?
13%
What is the estimated percentage of prostate cancer incidence in men?
20%
What is the estimated percentage of breast cancer incidence in women?
30%
What is the estimated percentage of colon and rectum cancer incidence in men?
9%
What is the estimated percentage of colon and rectum cancer incidence in women?
7%
What is the estimated percentage of lung and bronchus cancer deaths in men?
24%
What is the estimated percentage of lung and bronchus cancer deaths in women?
23%
What is the estimated percentage of prostate cancer deaths in men?
10%
What is the estimated percentage of breast cancer deaths in women?
15%
What is the estimated percentage of colon and rectum cancer deaths in men?
9%
What is the estimated percentage of colon and rectum cancer deaths in women?
8%
How many cancer-related deaths occur worldwide annually?
9.5 million deaths worldwide
Which four types of cancer constitute more than 50% of diagnoses?
Lung, female breast, prostate, and colon/rectum cancer
What age group has the highest incidence of cancer?
Most cases occur in individuals older than 55 years of age.
What is the leading cause of death among women aged 40 to 79?
Cancer
What is the leading cause of death among men aged 60 to 79?
Cancer
What percentage of all deaths in individuals younger than 15 years old are due to cancer?
10%
What are the three most common cancers in children younger than 15 years old?
Acute leukemia, neuroblastoma, and retinoblastoma
What is a precursor lesion?
A localized morphologic change that identifies a field of epithelium at increased risk of malignant transformation.
How does chronic inflammation relate to cancer risk?
It increases cancer risk in individuals affected by various chronic inflammatory diseases, both infectious and noninfectious.
What is an inherited genetic change related to cancer?
A genetic change that increases cancer risk and can be passed down if present in a parent's egg or sperm cells.
APC gene is associated with
colorectal cancer (FAP)
gene BRCA1/BRCA2 is associated with what condition
BRest, prostate CAncer
DCC
associated condition - colorectal cancer
gene SMAD4 (DPC4) is associated with what condition
pancreatic cancer, colorectal cancer
Gene PTEN is associated with what condition
prostate, breasT
gene RB1
associated condition: Retinoblastoma.
gene TP53 is associated with what condition
multiple malignancies Breast/Brain, Lung/Leukemia, Adrenal gland.
What is a precursor lesion?
A localized morphologic change that identifies a field of epithelium at increased risk of malignant transformation.
How does chronic inflammation related to cancer risk?
It increases cancer risk in individuals affected by various chronic inflammatory disease, both infectious and noninfectious.
What is an inherited genetic change related to cancer?
A genetic change that increase cancer risk and can be passed down if present in a parent’s egg or sperm cells.
RB1
Associated with Retinoblastoma
TP53
Known as the "Guardian of the Genome"
TP53 Function
Regulates cell cycle progression, DNA repair, cellular senescence, and apoptosis
TP53 Mutation
Most frequently mutated gene in human cancers 🚨
What factors can cause DNA damage leading to p53 activation?
ionizing radiation, carcinogens, and mutagens.
what happens when p53 detects DNA damage?
it accumulates, binds to DNA, and activates transcription-dependent and independent targets
What are the possible cellular responses when p53 is activated?
-Senescence (permanent cell cycle arrest)
-G1 arrest and DNA repair (via p21 and GADD45)
-Apoptosis (BAX and PUMA if repair fails)
what happens if p53 is mutated or lost?
p53 dependent genes are not activated
-no cell cycle arrest, no DNA repair, no senescence
-mutant cells accumulate mutations
-leads to malignant tumor formation
What are two key proteins involved in p53-mediated apoptosis?
BAX and PUMA (pro-apoptotic proteins)
Environmental Factors & Lung Cancer
90% of lung cancers are caused by environmental factors
alcohol Smoking & Cancer Risk
Affects mouth, esophagus, pancreas, and bladder
Pharynx & Larynx Cancer Risk increased by
alcohol Increases risk of pharynx carcinoma, larynx, and esophagus cancer
Cancer Risk Increase by Gender unhealthy food intake environmental factors
52% in males 🔹 62% in females
Estrogen & Cancer Risk
Lifelong estrogen exposure increases risk of breast & endometrial cancers
toxin: Arsenic
Organ: lung
toxin: asbestos
Organ: lungs
toxin: Tobacco smoke
Organ: lung
toxin: ethanol
organ: breast
toxin: nickel, chromium beryllium, silica
organ: lungs
toxin: Radon
organ: lungs
what are the cellular and molecular hallmarks of cancer?
-sustaining proliferative signaling.
-enabling replicative immortality
-Tumor-promoting inflammation
__
-evading growth suppressors
-genome instability
__
-avoiding immune destruction
-resting cell death
__
-activating invasion & metastasis
__
-inducing or accessing vasculature
-deregulating cellular metabolism
Warburg Effect
Cancer cells exhibit altered metabolism
Glucose & Cancer Metabolism
Cancer cells use high levels of glucose for energy
Fermentation in Cancer Cells
Glucose → Lactate even in the presence of oxygen (aerobic glycolysis)
How does glucose metabolism differ in differentiated vs. proliferaating tissue?
Differentiated tissue: uses oxidative phosphorylation when oxygen is available. and anaerobic glycolysis when oxygen is absent.
Proliferating Tissue (including cancer cells): uses aerobic glycolysis (Warburg effect), favoring lactate production regardless of oxygen availability.
What enzyme is involved in converting pyruvate to lactate in proliferating tissues?
LDHA (Lactate Dehydrogenase A)
What is the main ATP-generating process in normal differentiated cells under oxygen-rich conditions?
Oxidative phosphorylation
Why do cancer cells favor aerobic glycolysis over oxidative phosphorylation?
It allows for rapid ATP production and provides intermediates for biosynthetic pathways needed for cell growth
what metabolic shift occurs when differentiated cells lack oxygen?
They switch from oxidative phosphorylation to anaerobic glycolysis producing lactate.
What is the role of the PDH (pyruvate dehydrogenase) complex in metabolism?
It directs pyruvate into the mitochondria for oxidative phosphorylation in oxygen-rich conditions.
gene: ALK associated neoplasm
lung adenocarcinoma
gene: EGFR (ERBB1) associated neoplasm
lung adenocarcinoma
gene: HER2 (ERBB2) associated neoplasm:
lung adenocarcinoma
Gene: HER2 (ERBB2) Associated neoplasm:
Breast
gene: BRAF associated neoplasm
colorectal
Gene: KRAS assocaited neoplasm
colorectal and lung
Oncoproteins
Signal pathways that drive cell proliferation
Growth Factors & Oncoproteins
Growth factors promote cell growth and division
Growth Factor Receptors
Growth factor receptors trigger signaling pathways for cell proliferation
Loss of TP53 Function
Prevents upregulation of PUMA (pro-apoptotic protein), allowing cells to survive DNA damage
BCL2 Overexpression
Overexpression of anti-apoptotic BCL2 family proteins protects tumor cells from apoptosis
Evasion of Cell Death in Tumors
Loss of TP53 + BCL2 overexpression help tumor cells avoid apoptosis
What is the role of growth factor receptors in cell signaling?
Growth factor receptors activate intracellular signaling pathways that promote cell growth, metabolism, and survival
Tumor Markers
Increased levels of tumor markers can indicate cancer presence
CA15-3/CA27-29
Important markers for breast cancer
CEA
Important marker for colorectal cancer
PSA
Important marker for prostate cancer
Molecular Profiles of Tumors
DNA sequencing has greatly impacted cancer evaluation
RNA Sequencing in Cancer
Widely used in research laboratories for cancer studies
Advances in Cancer Genomics
Enables systematic sequencing and cataloging of genomic alterations in cancers
Impact Zones of Molecular Profiling
Research 🔹 Targeted therapies
General Characteristics of Tumors
Parenchyma (neoplastic cells) & Reactive stroma (non-neoplastic)
Benign Leiomyoma
Small, well demarcated
Slow growing, non-invasive
Non-metastatic, well-differentiated
Malignant Leiomyosarcoma
Large, poorly demarcated
🔹 Rapidly growing, with hemorrhage and necrosis
🔹 Locally invasive, metastatic
🔹 Poorly differentiated
Local Invasions
nearly all bening tumors grow massses that remain localized to their site of origin and lack the capacity to invade distant sites
Metastasis
spread of a tumor to sites that are physically discontinuous with the primary tumor
Morphological changes- differentiation
extend to which. neoplastic parenchymal cell resemble the corresponding parenchymal cells
morphological anaplasia
lack of differentaition
