What is Cancer?

When cells in the body grow out of control and there is no mechanism to control it, a tumour forms (Tumour literally means a "lump"). If this tumour just grows larger and larger and stays confined to the area it starts in, it is called Benign, however, if cells spread from this Primary Tumour along the blood stream or the lymphatic channels, they can deposit in other sites in the body and thus it becomes a Malignant Tumour, ie Cancer.

In the case of Lung Cancers, these deposits around the body (Metastases) can occur in the Liver, Bones, Lymphnodes, Brain or Adrenal glands. Assessment of the Primary cancer entails assessment for possibility of spread to these sites and so clinical examination along with special scans are needed for this.

Cancer is a genetic disease that results from multiple changes in genes. These changes ultimately lead to the deregulation of the cell cycle mechanism and to uncontrolled cell proliferation. Cancer development involves 4 types of genes:

  1. oncogenes
  2. tumour suppressor genes
  3. mutator genes
  4. apoptotic genes (programmed cell death)

In lung cancers, sequential accumulation of specific genetic changes occur, namely:

  1. deletion of the short arm of chromosome 3 (3p).
    (FHIT gene at chromosome 3p plays a critical and early role in lung carcinogenesis.)
  2. inactivation of tumour-suppressor genes TP53, CDKN2 and RB
  3. deregulated expression of EGER and HER2/neu oncogenes
  4. alteration in expression of proteins involved in apoptosis (programmed cell death) control
    - i.e. Bcl2 as well as point mutations in KRAS2 and amplification of myc oncogene family members

Malignant change of a normal lung cell results from multiple genetic aberrations,and ones which are frequently associated with human lung cancer are ras , erb-B2, and MYC, JUN and FOS families of protooncogenes.

In an experiment on mice, the mutational spectra of RAS was analysed after exposure to benzpyrene - a carcinogenic ingredient of cigarette smoke. Cells which acquired the mutations in both p53 and KRAS lost the G1 arrest phase of the cell cycle, and being unchecked, grew with progressive cellular dysregulation leading to actual cancer.

erb-B2 overexpression in lung cancers has been found to be associated with a shorter survival time for adenocarcinomas as well as larger tumour size and higher stage at presentation. As this overexpression is involved in carcinogenesis it may be an area to target for therapies.

The MYC proteins are important regulators of cell proliferation and the MYC genes also play key roles in differentiation and apoptosis (planned cell death).

The activating protein-1 (AP-1) family of transcription factors is composed of JUN, FOS and ATF (activating transcription factor) proteins. The involvement in lung cancers is sparse but may be implicated.

Cancer formation then, is a sequence of processes in which cells become malignant by multiple genetic alterations affecting the cell growth, differentiation and survival Cigarette and tobacco smoke contain multiple chemicals which bind covalently to DNA and thus trigger genetic mechanisms of cancer generation.

In order to stop tumour formation, the human body has mechanisms to protect against the uncontrolled growth of cells - one such mechanism involves the tumour suppressor gene p53. Once this gene is activated, it initiates either cell cycle arrest or programmed cell death (apoptosis). Studies on the p53 protein have shown that it has many chemicals acting on it and it acts on many chemicals in the cell itself, and is implicated in the recognition and repair of DNA damage. Studying the signalling pathways that regulate and are regulated by p53 will enhance our understanding of development of lung cancers.

Chemotherapy and radiation both act to kill the cancer cells, but as time moves on and more information accumulates, it appears that more drugs which are target specific may be developed with dramatic effect. Overall, prevention by smoking cessation should reduce the incidence of cancers and is the single most important area in lung cancer control at the present time.