COURSE DESCRIPTION

The development of cancer is a multi-step process that comprises gene mutations caused by environmental factors, biological agents or hereditary predispositions. These mutations might cause cells to bypass cell cycle checkpoints. Normally, two groups of genes are involved in regulating cell division: tumour suppressor genes and proto-oncogenes. Mutations in either or both of these groups of genes may lead to the development of cancer. Cancer has a much higher incidence in Singapore compared to other diseases and accounts for as much as 30 per cent of the deaths in this country. The recorded incidence of cancer is on the rise and this could be due to the accumulation of mutations from one generation to the next, although other reasons have also been proposed: increased exposure to carcinogens and increased detection rates as a result of effective cancer screening programmes. As such, an understanding of how cancer develops is important as this would set the platform for discussion of developing anti-cancer drugs.

Learning Outcome

Candidates should be able to:

2(p) identify the causative factors, including genetic, Chemical carcinogens, ionising radiation and loss of immunity, which may increase the chances of cancerous growth

2(q) explain how the loss of function mutation of tumour suppressor genes, including/p53|, and gain in function mutation of proto-oncogenes, including ras, results in uncontrolled cell division

2(r) describe the development of cancer as a multi-step process that includes accumulation of mutations, angiogenesis and metastasis

Use the knowledge gained in this section in new situations or to solve related problems

CONTENT PAGE

1. Introduction to Cancer

1.1 Cancer terminology

1.2 Important characteristics of cancer

1.3 Tumours can be benign or malignant

2. Uncontrolled cell division could result in cancer

2.1 Cell cycle

2.2 Cell cycle checkpoints

2.3 Role of cyclins & cyclin-dependent protein kinase in cell cycle

2.4 Mutations in genes controlling cell cycle

2.4.1 Tumour Suppressor Gene

2.4.1.1 Loss of Function mutation of tumour suppressor gene

2.4.1.2 p53, a tumour suppressor gene

2.4.1.3 p53 protein is involved in the cell cycle-inhibiting pathway

2.4.2 Proto-oncogene & Oncogene

2.4.2.1 Gain in Function mutation of proto-oncogene

2.4.2.2 ras, a proto-oncogene

2.4.2.3 ras protein is involved in the cell cycle-stimulating pathway

2.4.2.4 Consequences of conversion of proto-oncogene to oncogenes

3. Multi-step Model of Cancer Progression

3.1 Accumulation of mutations

3.2 Activation of telomerase

3.3 Angiogenesis

3.4 Metastasis

3.5 Case study – Hereditary Colorectal Cancer

3.5.1 Sequence of mutation accumulation in colorectal cancer

3.6 Case study – Breast Cancer

3.6.1 Development of breast cancer

4. Causative Factors of Cancer