Module 2.1 - Intro to cancer

Cancer

collection of related diseases, uncontrolled growth of abnormal cells

Neoplasm

abnormal tissue formed when cells grow & divide more than should/don't die, can be harmless OR cancerous

Tumour

swelling/abnormal enlargement, non-specific term for neoplasm, can be benign or malignant

Benign Tumor

harmless, no invade/spread, smooth & round

Malignant Tumor

cancerous, invade/spread (metastasis), spiky

How are tumors classified?

By tissue of origin

Carcinoma

epithelial cells

sarcoma

tissues that support & connect body

lymphoma

lymphocytes

glioma

brain connective tissues

leukemia

blood & bone marrow cells

Risk factors for Cancer

Family History, Tobacco, Aging, UV radiation

Why can tissue injury cause cancer?

injury -> repair by stem cells which go from resting state to persistent activation -> cancer

Oncogenic mutation

contribute to development of cancer

Development of cancer steps

transformation (normal cell -> tumor cell), progression (tumor cells accrue mutations ->variants), proliferation (more mutations -> more subclones), tumour heterogeneity (many diff cancer cells in same tumor)

What is the challenges of treating heterogenous tumors?

Different cells respond to different treatment

Oncogenes

mutated from proto-oncogenes = selective growth advantages, gain of function mutations (gas pedal), only 1 copy need mutated

proto-oncogenes

involved in growth receptor pathways

ERBB-1 gene

proto-oncogene, codes for Epidermal Growth Factor Receptor (EGFR)

Epidermal Growth Factor Receptor (EGFR)

Tyrosine Kinase Receptor, detects ligands, binding leads to: angiogenesis, cell proliferation, inhibition of apoptosis, migration, adhesion, invasion

Types of mutations for EGFR

hyperactivation & constitutive activation

Hyperactivation (EGFR)

increase EGFR activity - same amount ligand binding, more: 2ndary messengers, signal to nucleus, gene expression

Constitutive Activation

signal even w/out stimulus, cannot be terminated, gene expression always on

Common Cancer therapies against EGFR

chemotherapy, antibodies (kill ligand), kinase inhibitors (disrupt signaling cascade)

Tumor suppressor genes

prevent too much growth, induce cell death (controlled apoptosis), part of cycle checkpoints

When tumor suppressor gene mutated...

disabled, loss of function mutation (brake pedal broken), both alleles must mutated

TP53 gene

tumor suppressor gene, codes for p53 protein

p53 protein

respond to genomic damage, activate repair/cell death programs, part of G1/S checkpoint (check damage before replication)

p53 deficient cells...

tolerate & thrive w/ oncogenic mutations

senescence

lose ability to replicate