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Understanding Resistance to new Cancer MAB Drugs

Posted Sep 09 2011 4:24am

“All patients will ultimately develop resistanceThe ability of a microbe, such as a type of bacteria, to resist the effects of antibiotics or other drugs. to cetuximab”, according to a recent report in the press. The question is – what does this actually mean for cancerAbnormal, uncontrolled cell division resulting in a malignant tumour that may invade surrounding tissues or spread to distant parts of the body. patients?  Cetuximab is a biologic drug which is used to treat colorectal cancer, head and neck cancers and some lung cancers. Specifically, Cetuximab is an antibodyOne of a group of special proteins in the blood that are produced in response to a specific antigen and play a key role in immunity and allergy. that targets a growth factorA chemical that stimulates new cell growth and maintenance in the body. (called EGRF) that would otherwise facilitate tumourAn abnormal swelling. growth, and so the news does not sound too good. There were high hopes for this form of new biologic treatment, so does this mean that hopes are dashed?

The researchers found that these resistantA microbe, such as a type of bacteria, that is able to resist the effects of antibiotics or other drugs. tumours replaced the EGFR route with a different one that involved a substitute proteinCompounds that form the structure of muscles and other tissues in the body, as well as comprising enzymes and hormones. called ERBB2. Therefore, even if the drug has knocked out EGRF, the resistant tumour simply switches to a different route. But the good news is that several other drugs which target ERBB2 have already been developed and approved. Therefore, by understanding drug resistance in tumours and how this varies from individual to individual it should be possible to provide a correctly targeted ‘best’ therapy. There are of course likely to be other ways in which cancers can become resistant,  this research is nonetheless an important step towards potentially providing effective treatments targeted to the needs of individual patients.

Antibodies are often used in medicine, especially in the form of vaccines. An antibody is a natural bloodA fluid that transports oxygen and other substances through the body, made up of blood cells suspended in a liquid. product that has many functions involved in maintaining a healthy immunity to things such as bacteriaA group of organisms too small to be seen with the naked eye, which are usually made up of just a single cell., virusesMicrobes that are only able to multiply within living cells. and cancers. The target for the antibody is called the ‘antigenA substance that prompts the immune system to fight infection with antibodies.’. To obtain antibodiesSpecial proteins in the blood that are produced in response to a specific antigen and play a key role in immunity and allergy. at sufficient quantities, traditionally people or animals can be ‘primed’ with a non-lethal dose of the antigen and they will mount an immune response, which may include raised levels of antibodies to the antigen which can then be separated in the laboratory from out of the subject’s blood samples. However, this is a relatively crude method of production and modern methods involve fusing the blood cellThe basic unit of all living organisms. that produces the antibody with a type of tumour cell so that large quantities of the antibody are produced in the lab, this is called a monoclonal antibody and due to their purity they are specific to only one antigen type. It is these laboratory produced antibodies that are now being used as MAB drugs.

When given to a patient the MAB will attach to a cancer cell or other element required by the tumour. Different MABs are designed for different functions depending on the type of cancer. For example:

  • MAB Seek and destroy - Cancers often escape the immune systemThe organs specialised to fight infection. because these cells are not foreign. The attachment of a MAB may expose the tumour and render it recognisable for what it is.
  • Knock out the production process – for example by attaching to and effectively disabling the tumour growth factors or by attaching to the receptors on the surface of cancer cells in order to block the growth stimulant.
  • Tumours need their own blood supply – the MABs may be used to block the growth signals needed by blood vessels.
  • Delivering a radioactive dose. By combining a radioactive particle with a MAB, radiationEnergy in the form of waves or particles, including radio waves, X-rays and gamma rays. can be delivered directly to the cancer cells.
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