Cancer

CANCER:

Cancer arises because certain cells within a given tissue escape from normal growth controls, replicate more frequently, and migrate to sites distant from the parent tissue where further uncontrolled replication occurs. Such escape is facilitated by the accumulation of mutations within a cancerous cell as a result of the innate and environmental carcinogens to which cellular DNA is subjected. If errors generated in coding DNA are not repaired, these will be transmitted to the daughter strands as the cell divides. Clearly, mutations will arise more rapidly if external mutagenic stimuli are increased, or if the cell is defective in DNA repair systems.

ONCOGENES:

This term refers to a gene which has been mutated to facilitate neoplastic growth. The normal function of such genes may be the synthesis of factors involved in growth control, the cell cycle or apoptosis. Oncogenes can be broadly divided into two groups, according to whether their oncogenic effect results from overactivity of a ‘proto-oncogene’ or the loss of a ‘tumour suppressor’ function.   

Proto-Oncogene:

The majority of known oncogenes are components of signal transduction pathways in which mutations or the presence of increased copies of a gene result in overactivity, mimicking persistent growth factor stimulation. These include genes encoding receptors (e.g. erbB in breast carcinoma), cytoplasmic signalling moieties such as K-ras, and transcription factors such as c-myc (important in gastrointestinal tumours and leukaemias). A recently described class encode mitotic spindle binding proteins; mutation in these genes promote premature exit from anaphase, leading to incorrect chromosome segregation to daughter cells, and anaploidy. In animals, a number of tumours are caused by retroviruses which carry activated oncogenes, but to date this has not been shown to be a common mechanism in human cancer. Nevertheless, several human cancers are undoubtedly caused by infectious agents. Important examples include human papillomavirus E7 (which inappropriately phosphorylates pRB), leading to cervical carcinoma; herpesvirus 8 (which encodes a cyclin that drives the host cell through the G1-S checkpoint); and Epstein-Barr virus, responsible for Burkitt’s lymphoma and nasopharyngeal carcinoma.   

By: DAVIDSON’S

      Principles and Practice of Medicine

      Eighteenth Edition