Week 8

Cancer is inappropriate cellular proliferation. Cancer is an abnormal state in which uncontrolled proliferation of one or more cell populations interferes with normal biological functioning Transformed cells generally display several or all of the following properties: spherical morphology expression of fetal antigens, growth-factor independence lack of contact inhibition, anchorage- independence growth to high density. Cancer can invade the body to different degrees. In the early stages, the abnormally proliferating cells are usually restricted to the area in which the cancer originated. Progressive changes in the cancer cells may allow them to escape from the primary site (metastasis), and cause damage to the body on a larger scale.

Cancer is one of the most common diseases in the developed world: 1 in 4 deaths are due to cancer 1 in 17 deaths are due to lung cancer Lung cancer is the most common cancer in men Breast cancer is the most common cancer in women There are over 100 different forms of cancer

Cancer arises from the mutation of a normal gene. Mutated genes that cause cancer are called oncogenes. A factor which brings about a mutation is called a mutagen. A mutagen is mutagenic. Any agent that causes cancer is called a carcinogen and is described as carcinogenic. So some mutagens are carcinogenic.

Benign tumours do not spread from their site of origin, but can crowd out (squash) surrounding cells eg brain tumour, warts. Malignant tumours can spread from the original site and cause secondary tumours. This is called metastasis. They interfere with neighbouring cells and can block blood vessels, the gut, glands, lungs etc.

To form a secondary tumour, a tumour cell needs to leave the vessel system and invade tissue. The cell must attach itself to a vessel’s wall. Once this is done, it can work its way through the vessel and enter the tissue.

Cancer Cells 1. Mutations occur in the DNA when it is replicated. 2. Chemical signals that start and stop the cell cycle are ignored. 3. Cells do not communicate with each other and tumours form.

A tumour marker is anything present in or produced by cancer cells or other cells of the body in response to cancer or certain benign (noncancerous) conditions that provides information about a cancer, such as how aggressive it is, whether it can be treated with a targeted therapy, or whether it is responding to treatment.

Produced exclusively by a cancer cell as a response to tumour development Sensitivity Not exclusively by a cancer cell, but has enough to be distinguished from production by a normal tissue cell Specificity

The quality should be included High sensitivity High specificity Can be qualified Safe Convenience Low price

Circulating tumour markers can be found in the blood, urine, stool, or other bodily fluids of some patients with cancer. Circulating tumour markers are used to: estimate prognosis detect cancer that remains after treatment ( residual disease) or that has returned after treatment assess the response to treatment monitor whether a cancer has become resistant to treatment Tumour tissue markers are found in the actual tumours themselves, typically in a sample of the tumour that is removed during a biopsy. Tumour tissue markers are used to: diagnose, stage, and/or classify cancer estimate prognosis select an appropriate treatment (eg, treatment with a targeted therapy)

Screening Diagnosis Staging Prognosis

Tumour markers play a limited role for Tumour screening, just because…. ›relatively low sensitivity ›lack of specificity and relation to Tumour size Inappropriate for the detection of small in situ cancer

The tumour markers and medical imaging are complementary in the pre-therapeutic and post- therapeutic staging

The pre-therapeutic level of certain tumour marker can contribute a prognostic factor because of links with… Metabolic activity tumour size Invasion More valuable in that it is independent of other usual prognostic factors for the pathology

High markers level before treatment generally Not only correlate very well with the therapeutic result but are sometimes superior to this result in the assessment of complete remission The assay must be considering the marker half-life when during treatment and all post-therapeutic re- evaluation

Specificity and sensitivity are neither sensitive nor specific enough to screen for or diagnose cancer without the support of other clinical findings. levels help determine the amount of cancer present.

1) tumour marker levels can be elevated in people with benign conditions; 2) tumour marker levels are not elevated in every person with cancer, especially in the early stages of the disease; 3) many tumour markers are not specific to a cancer 4) the level of a tumour marker can be elevated by more than one type of cancer (NCI, 2006).

is a single chain glycoprotein with a molecular weight of approximately 70,000 daltons. serum AFP concentrations remain low except during pregnancy, benign liver diseases, (hepatitis, cirrhosis), primary hepatocellular carcinoma, and certain germ cell tumours. An elevated level of AFP strongly suggests the presence of either primary liver cancer or germ cell cancer of the ovary or testicle. The most important application of AFP testing in cancer management is for testicular cancer. An AFP test can also be done to detect other, more rare conditions, such as chromosome (trisomy) syndromes or omphalocele, a congenital defect in which portions of a fetus’s intestines protrude through the abdominal wall.

AFP is not a screening test for cancer.

An oncofetal glycoprotein antigen. Carcinoembryonic antigen (CEA) is a normal cell product that is over-expressed by adenocarcinomas, primarily of the colon, rectum, breast, and lung. CEA levels may be measured during treatment with medicines to destroy cancer cells (chemotherapy). This provides information about how well the treatment is working. CEA testing is a reliable test for recurrent colon cancer if the original cancer produced this protein before treatment.

Glycoprotein produced in prostate epithelial cells. Its normal physiologic role is as a liquefying agent for seminal fluid; only a tiny amount leaks into the blood, therefore its normal serum level is usually very low. Elevated serum levels of PSA have been associated with prostate carcinoma. Elevated levels of Prostate-Specific Antigen (PSA) may be found in the blood of men with benign prostate conditions, such as prostatitis and benign prostatic hyperplasia (BPH), or with a malignant growth in the prostate.

to screen for choriocarcinoma in women who are at high risk for the disease, and to monitor the treatment of trophoblastic disease.

A high-molecular-weight glycoprotein found on the surface of Mullerian and coelomic epithelial-derived cell types, and is the best known tumour marker for epithelial ovarian cancer.

A protein made by a variety of cells, particularly breast cancer cells. CA15-3 levels can be higher than normal with cancerous and non-cancerous conditions. CA15-3 is most often increased in breast cancer that has spread to other parts of the body.