Module 3: Neoplasms and Cancer

A neoplasm is an abnormal growth of new tissue, also known as a tumor
Two types of tumors:
- Benign: slow-growing, well-differentiated cells, well-organized stroma, no metastasis
- Malignant: rapid growth, loss of differentiation, invasion of surrounding tissues, and metastasis
Characteristics of malignant tumors:
- Loss of control of growth
- Anaplasia (loss of tissue organization)
- Invasion of local tissues
- Metastasis

Genetic instability: high frequency of mutations in cancer cells
Independent growth: cancer cells make their own growth signals and don't require external signals
Loss of contact inhibition: cancer cells continue to grow and pile up on top of each other
Decreased cell adhesion: cancer cells have fewer membrane structures to stick together, allowing them to be shed and metastasize
Loss of anchorage dependence: cancer cells can survive and grow without attachment to an underlying matrix
Production of unusual antigens: cancer cells produce cell surface markers, enzymes, or hormones that are not made by normal tissue
Immortal: cancer cells can divide without limit due to telomerase activity
Altered metabolism: cancer cells use anaerobic respiration, producing lactic acid, and requiring more glucose

The spread of cancer cells from the original site to distant organs and tissues
Local spread: cancer cells invade surrounding tissues, breaking down cells and connective tissue
Distant spread: cancer cells invade lymph and blood vessels, and travel to new sites
Process of metastasis:
1. Cancer cells evolve characteristics needed to metastasize
2. Initial invasion of local tissue
3. Entry into lymphatic or blood vessels
4. Survival and evasion of the immune system
5. Penetration of tissues at new sites
6. Seed and grow at new sites

Compression: e.g. brain tumor causing headaches, nausea, and loss of consciousness
Obstruction: e.g. blockage of airways or gut
Infarction: growth of tumor causing local necrosis of tissues
Hemorrhage: damage to blood vessels causing bleeding
Rupture or perforation: e.g. gut or ovary
Effusions: excessive fluid in pleural, pericardial, or peritoneal spaces

Paraneoplastic syndromes: symptoms triggered by a cancer, but not caused by direct local effects
Pain: little or none in early stages, can be strong in later stages
Fatigue: not relieved by sleep or rest
Cachexia: loss of body mass due to metabolic disturbances
Anemia: caused by chronic bleeding, malnutrition, chemotherapy, and malignancy in blood-forming organs
Leukopenia and thrombocytopenia: caused by tumor invasion of bone marrow, chemotherapy, and radiation therapy
Infection: most significant cause of complications and death
GI tract: relies on rapidly multiplying tissue, which is affected by chemotherapy and radiation therapy
Hair and skin: affected by therapeutic agents

A small number of changes in the genetic material of the cell
Accumulation of mutations over a lifetime
Types of changes in genes:
- Changes in the actual DNA
- Changes in metabolic pathways
- Changes in the control mechanisms that govern gene expression (epigenetics)

Inflammation: chronic inflammation increases the risk of cancer
Viral and bacterial infections: associated with cancer, e.g. HBV and HCV with liver cancer, HPV with cervical cancer
Environmental and lifestyle interactions: e.g. cigarette smoking, poor diet, obesity, lack of exercise
Population-based studies: regions of highest incidence of different types of cancer

Only 10-20% of all cancers linked to heritable factors
Inherited factors: e.g. BRCA1 and BRCA2 mutations
Proportion of women with a BRCA1 or BRCA2 mutation that develop breast cancer by a given age### Heredity and Cancer
Some inherited conditions increase the risk of cancer
Chemical carcinogens in the workplace can increase cancer risk
Combination of alcohol and cigarettes increases the risk of esophageal cancer by 40 times

Initiation: exposure to carcinogenic agents, resulting in irreversible mutations to the genome
Promotion: cytokines and growth factors induce cell proliferation
Progression: tumor cells acquire characteristics to invade and metastasize to other tissues

Tumor markers: substances produced by tumor cells, used to identify high-risk individuals, diagnose tumors, and monitor treatment success
Cytology/Histology: examination of secretions surrounding tumors, biopsy, and immunohistochemistry to detect abnormal cells
Imaging: endoscopic, ultrasound, X-rays, CT, MRI, and PET scans to visualize tumors

Three main treatments: chemotherapy, radiation therapy, and surgery
Chemotherapy: targets metabolic pathways, used in combinations to decrease side effects and increase attack on cancer cells
Radiation therapy: targets cells that are rapidly renewing, used for localized tissues in areas hard to reach surgically
Surgery: often the definitive treatment for localized tumors, used prophylactically in some cases

Cancer is rare in children, but the second leading cause of death in children 1-14 years old
Types of cancer in children are different from adults, including leukemia, brain, and sarcoma
Causes of childhood cancer are largely unknown, but some genetic risk factors and environmental exposures have been implicated
Early detection is difficult, but more than 70% of children diagnosed with cancer are cured