“As a Cancer doctor, I’m looking forward to being out of a job” Daniel Kraft

Cancer is a collection of different diseases and displays uncontrolled growth of abnormal cells, causing a primary tumour (the initial site of the tumour). A benign tumour will remain localized and is usually surrounded by a fibrous capsule, whereas a malignant tumour will infiltrate and metastasize.

Cancer development

   

     Initiation (carcinogen)                 Promotion                     Progression                   Metastasis

                    ↓                                          ↓                                    ↓                                  ↓

Normal cell →       Transformed cell       →       Tumour cell         →       Cancer cell        →    Cancer cell  

                          (metaplasia hyperplasia)    (hyperplasia benign)  (anaplasia malignant)  (anaplasia secondary)

What causes cancer? The acquisition of mutations such as inborn zygotic mutations, somatic mutations, or from the external such as viruses, chemical and radiation.

Phenotypes of malignant cancer cells

Cancer cells have a loss of growth control, normal cells need external signals from growth factor to divide, whereas cancer cells are not dependent on normal growth factor signalling. The acquired mutations shorten circuit growth factor pathways leading to unregulated growth (autocrine signalling, deregulation of receptor firing). Normal cells also respond to inhibitory signals to maintain homeostasis, acquired mutations in cancer cells interfere with the inhibitory pathways. Cancer cells are able to maintain the length of telomeres, allowing unlimited replicative potential and a resistance to apoptosis. 85% of tumours show upregulated expression of telomerase, in vitro telomerase can transform fibroblasts to cancer cells (tumourigenesis). The evasion of apoptosis means the body is unable to eliminate the cancer cells. The tumour stroma is able to induce angiogenesis, allowing the tumour access to nutrients and the removal of metabolic waste. Some anti-angiogenic cancer therapies such as anti-vascular endothelial growth factor (anti-VEGF) are able to reduce cancer growth. Normal cells maintain their location in the body and generally do not migrate, however cancer cells are able to migrate to other parts of the body.

What are caretakers and gatekeepers?

Caretakers are tumour suppressor genes or proteins that act to protect the genome from damage or mutation. Many caretaker genes encode proteins that recognize or repair DNA damage. Gatekeepers are tumour-suppressor genes that regulate cellular responses that prevent the survival or proliferation of potential cancer cells. These responses are apoptosis and cellular senescence.