patho2 exam 1 : Biology of cancer

Cancer Incidence and Overview

• Cancer incidence in the US: pancreas and ovary have lower incidence, but a higher percentage of deaths among those who develop these cancers
• Breast and prostate cancers are more survivable than lung and bronchus cancers
• Cancer is a disease caused by uncontrolled division of abnormal cells in a part of the body
• Cancer is a collection of more than 100 different diseases, each caused by a specific and often unique age-related accumulation of genetic and epigenetic alterations

Inheritance of Cancer

• There are heritable cancer syndromes
• The majority of cancers are not familial
• Cancer is a genetic disease, but the majority of mutations that lead to cancer are somatic (i.e., they happen in body cells, not in germ cells)

Hallmarks of Cancer

• 8 Hallmarks and 2 traits that enable cancer progression
• The hallmarks of cancer include:
  • Avoiding immune destruction
  • Sustaining proliferative signaling
  • Deregulating cellular energetics
  • Resisting cell death
  • Inducing angiogenesis
  • Genomic instability (mutator phenotype)
  • Activating invasion and metastasis
  • Tumor-promoting inflammation
  • Enabling replicative immortality
  • Evading growth suppressors

Causes of Genetic Mutations

• Viruses (e.g., HPV increasing risk of cervical cancer)
• Bacteria (e.g., chronic H. pylori increasing risk for gastric adenocarcinoma)
• Chemicals (e.g., smoking increasing risk for lung cancer)
• Radiation (e.g., UV and ionizing radiation increasing risk of skin cancer)

Multiple Hits Lead to Cancer

• Exposure, infection, or mutation can render a "hit"
• Sometimes, one exposure can render just "half a hit"
• Sometimes, a single exposure can pack two "hits" within it
• Some people are born with one or more "pre-existing hits"

Sustained Proliferative Signaling

• First and foremost, hallmark of cancer is uncontrolled cellular proliferation
• Cancer cells do not obey or require normal signals for cell division
• Cancer cells have the ability to divide indefinitely

Cell Division

• Checkpoints are found at G1, S, and M (in Metaphase of M)
• G1 checkpoint: cell checks that DNA is undamaged and resources are available
• S checkpoint: checks DNA for errors
• M checkpoint: checks that all sister chromatids are attached to mitotic spindles

Proto-oncogenes and Oncogenes

• Proto-oncogenes are genes that encode components of pathways that regulate normal cell proliferation
• Oncogenes are mutated or overexpressed proto-oncogenes
• Oncogenes are independent of normal regulatory mechanisms
• Example: HER2/neu gene, which encodes for a growth factor receptor

Translocation Mutations

• Can activate oncogenes in two ways:
  • Causing an excess production of a proliferative factor
  • Leading to production of novel proteins with growth-promoting properties
• Example: t(8;14) translocation leading to Burkitt Lymphoma

Tumor-Suppressor Genes

• Jobs: normally regulate the cell cycle, inhibit proliferation from growth signals, stop cell division when cells are damaged, and prevent mutations
• In cancer: oncogenes are activated and tumor suppressor genes are inactivated
• Examples: Rb and p53 genes

Evading Growth Suppressors

• Tumor-suppressor genes, such as RB, monitor antigrowth cellular signals and block activation of the growth/division phase in the cell cycle
• Mutations in RB lead to persistent cell growth

Inducing Angiogenesis

• Angiogenesis is the process of establishing new blood vessels
• Importance of blood supply for the growth and spread of cancer
• Example: VEGF (vascular endothelial growth factor)

Resisting Cell Death

• Apoptosis: programmed cell death
• Mechanism by which cells can self-destruct if needed during tissue remodeling or to protect against abnormal cell growth
• Two pathways to apoptosis: intrinsic and extrinsic

Tumor Markers

• Substances produced by both benign and malignant cells
• Examples: hormones, enzymes, genes, antigens, and antibodies
• Uses: screening, diagnosis, and following the clinical course of a tumor

Cancer Treatments

• Surgery: allows us to obtain tissue for diagnosis and staging of disease
• Radiation therapy: used to kill cancer cells while minimizing damage to normal structures
• Chemotherapy: attacks rapidly dividing cells
• Immunotherapy: emerging cancer treatment area
• Targeted disruption of cancer: designed to address unique growth characteristics of a specific class of tumor

Tissue Pathology of Cancer

• Definitions: neoplasm/tumor, malignant, benign, and cancer
• Characteristics of benign and malignant tumors
• Cancer classification: based on tissue and organ of origin, extent of distribution, microscopic appearance, and critical genetic changes

Progression to Malignancy

• Cancers develop incrementally as they accumulate genetic mutations
• Dysplasia: a premalignant condition
• Carcinoma in situ (CIS): preinvasive epithelial tumors
• Three fates: remain stable, progress to invasion or metastasis, or regress or disappear