Lec 3

Molecular Basis of Diseases - CANCER

Introduction to Cancer

• Cancer is a disease characterized by uncontrolled cell growth that can spread throughout the body.

• It can originate from almost any cell type in the human body consisting of trillions of cells.

• Normal cell division involves growth, replacement of old or damaged cells; cancer disrupts this orderly process.

Tumors

• Tumors can be cancerous (malignant) or non-cancerous (benign).

• Cancerous tumors invade nearby tissues and can metastasize to distant sites.

• Many cancers form solid tumors, except for blood cancers (e.g., leukemias).

Differences between Cancer Cells and Normal Cells

• Cancer cells grow without external signals; normal cells need these signals.

• Cancer cells ignore stop signals, invade other areas, and hijack the blood supply for nutrients.

• They can evade the immune system and accumulate genetic changes leading to uncontrolled growth.

How Does Cancer Develop?

• Cancer is primarily a genetic disease caused by alterations in genes regulating cell function.

• Genetic changes may arise from:

  • Errors during cell division.

  • Environmental damage (e.g., from tobacco, UV rays).

  • Hereditary factors.

• Risk of cancer increases with age due to reduced capacity to eliminate damaged cells.

Tumor Microenvironment

• Involves various immune cells, fibroblasts, and blood vessels that influence tumor growth and spread.

Types of Genes that Cause Cancer

• Proto-oncogenes: Normal role in cell growth; mutations can lead to cancer-causing oncogenes.

• Tumor Suppressor Genes: Control cell division; mutations can lead to uncontrolled growth.

• DNA Repair Genes: Fix DNA errors; mutations result in further genetic instability.

Metastasis

• Metastatic cancer retains the name of the original cancer (e.g., metastatic breast cancer in lungs).

Non-Cancerous Tissue Changes

• Hyperplasia: Increased cell number with normal appearance.

• Dysplasia: Abnormal cell appearance with potential for cancer development.

• Carcinoma in situ: Abnormal cells that do not invade but may become cancerous.

Types of Cancer

1. Carcinoma: Common, arising from epithelial cells (e.g., adenocarcinoma).

2. Sarcoma: Forms in bone and soft tissues (e.g., osteosarcoma).

3. Leukemia: Bone marrow cancers not forming solid tumors; abnormal white blood cells dominate.

4. Lymphoma: Begins in lymphocytes; includes Hodgkin and non-Hodgkin lymphoma.

5. Multiple Myeloma: Arises in plasma cells; leads to bone tumors.

6. Melanoma: Starts in melanocytes; can occur on skin or in pigmented tissues.

7. Brain and Spinal Cord Tumors: Named based on the cell type in the CNS.

8. Germ Cell Tumors: Form from reproductive cells; can be benign or malignant.

9. Neuroendocrine Tumors: Release hormones and can be benign or malignant.

Hallmarks of Cancer

• Key characteristics driving tumor growth include:

  • Sustained proliferative signaling

  • Evasion of growth suppressors

  • Resistance to cell death

  • Replicative immortality

  • Angiogenesis and invasion/migration of cancer cells

Oncogenes and Tumor Suppressor Genes

• Oncogenes promote excessive growth when activated (point mutations, amplifications).

• Tumor suppressor genes inhibit cell proliferation; inactivation contributes to tumor development.

Genetic and Epigenetic Alterations in Cancer

• Genetic alterations include point mutations, translocations, and amplifications affecting gene function.

• Epigenetic changes (DNA methylation, histone modifications) affect gene expression without altering sequence.

• Non-coding RNAs can also play a role in regulating cancer-related processes.

Targeted Therapies for Cancer

• Kinase Inhibitors and Monoclonal Antibodies: Target specific proteins or pathways (e.g., trastuzumab for HER2-positive breast cancer).

• Emerging Therapies: Include PARP inhibitors and immunotherapies utilizing the immune system against cancer.

• Personalized Medicine: Tailors treatment based on individual genetic profiles.