Neoplastic Disease and Cancer Notes

Cancer is a disease characterized by unregulated cell growth due to genetic mutations.
It is not a single disease; rather, it encompasses a broad family of diseases that can manifest in any part of the body.
Definition: A disease caused by uncontrolled division of abnormal cells.
Typical prognosis without treatment is fatal due to:
- Continuous cell proliferation disrupting normal cellular function.
- Crowding out healthy cells.
Statistics:
- In 2018, there were 18 million diagnoses and 9.6 million deaths globally.
- Up to 50% of the population may develop cancer at some point in life.

Benign Tumours:
- Small, slow-growing, non-invasive.
- Well-differentiated and localized; cannot metastasize.
Malignant Tumours:
- Large, fast-growing, invasive, and poorly-differentiated.
- Capable of metastasizing and infiltrating adjacent tissues.

Normal cell division is controlled by signals from growth factor receptors; they undergo apoptosis when signaling ceases or DNA is damaged.
In cancer cells, mutations disrupt these controls, leading to uncontrolled growth:
- They may proliferate without detecting neighboring cells.
- They can produce their own growth signals and ignore apoptotic processes.

A cancer cell might take about 2.5 years to grow into a detectable grape-sized tumor, dividing approximately every 2-6 weeks.
- Tumor size indicators:
- 1 million cells ≈ head of a pin.
- 1 billion cells ≈ small grape.

Invasion: Cancer cells spread from the primary site, needing changes to a migratory phenotype and using enzymes to degrade the extracellular matrix (ECM).
Metastasis: Tumor cells travel via the circulatory system to distant sites (commonly: bone, liver, brain, lungs, lymph nodes) forming secondary tumors.
- Most cancer-related deaths are due to metastatic disease.

Tumors need oxygen and nutrients; lack of these can create a necrotic core within larger tumors.
Tumors secrete factors like VEGF to stimulate blood vessel growth (angiogenesis) towards them. This can be targeted with anti-angiogenic therapy.

The transformation of normal cells into cancer cells involves multiple genetic changes and can encompass:
- Changes in cell morphology and behavior
- Developments like hyperplasia and dysplasia
- Formation of localized tumors termed "carcinoma in situ" which may progress to malignancy.

Oncogenes: Mutated forms of proto-oncogenes that promote cancer when activated (turned ON).
Tumor Suppressor Genes: Normal genes that, when inactivated (turned OFF), can lead to cancer by failing to control cell division or repair DNA damage.
Major genes include:
- C-myc: transcription factor.
- Ras: GTPase proteins.
- P53: cell cycle regulator and apoptosis inducer.
- BRCA1 & BRCA2: linked to breast and ovarian cancer.

Cancer may arise through two mutations:
- Hereditary Tumors: One mutation inherited and one acquired.
- Sporadic Tumors: Both mutations acquired.

Simultaneous mutations in oncogenes (p53 and Ras) can exacerbate cancer development through collaborative gene expression.

Types:
- Physical: Radiation exposure.
- Chemical: Mutagens like benzopyrene or aflatoxins.
- Biological: Viral and bacterial agents.

Viral: Can promote cancer via mechanisms such as degrading tumor suppressor genes or inducing chronic inflammation.
- Notable viruses include HPV, HTLV, HBV, and Helicobacter pylori in stomach cancer.

Approximately 5-10% of cancers have hereditary components.
Indicators of hereditary linkage include:
- Rare cancers, early onset cancers, multiple cancer types in individuals, familial patterns.
- Examples of genes involved: APC (colon), BRCA1/2 (breast), MET (renal).