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New Target To Combat Cancer? Defects In Pathway Underlying Fanconi Anaemia Can Cause Cancer In Non-FA Patients

Date:
May 20, 2009
Source:
NWO (Netherlands Organization for Scientific Research)
Summary:
In patients with Fanconi anaemia (FA), one of the DNA repair mechanisms that normally protects us against cancer no longer works adequately. A Dutch researcher set out to find the genes responsible for this defect. He discovered a new FA gene and established that FA gene defects could also cause cancer in people who do not suffer from FA. Although this does not sound positive, it is in fact good news. That is because cells with a FA defect are hypersensitive to certain types of chemotherapy and can therefore be specifically targeted.

In patients with Fanconi anaemia (FA) one of the DNA repair mechanisms that normally protects us against cancer no longer works adequately. Dutch researcher Najim Ameziane set out to find the genes responsible for this defect. He discovered a new FA gene and established that FA gene defects could also cause cancer in people who do not suffer from FA. Although this does not sound positive, it is in fact good news. That is because cells with a FA defect are hypersensitive to certain types of chemotherapy and can therefore be specifically targeted.

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DNA is continuously damaged. This is normally not a problem because our proteins repair the damaged DNA. However, in patients with FA that is a different story. They have a congenital defect as a result of which the DNA is not repaired. Therefore errors accumulate. These errors can result in uncontrolled cell division. Many patients are therefore confronted with cancer at an early age.

Thirteen different genes, including the well-known breast cancer gene BRCA2, can cause FA if any one of these is defective. These thirteen genes code for proteins that function in a biochemical pathway, the so-called Fanconi anaemia (FA) pathway, to repair the DNA. FA patients have a defect in one of these 13 proteins, as a result of which the pathway no longer functions and they run a high risk of developing cancer. However, now the question is whether errors in this pathway can also cause cancer in patients without FA.

Targeted treatment

To determine whether errors in the FA pathway in people without FA can cause cancer, all of the genes involved in that pathway need to be identified. Before Ameziane started his PhD research, only eight of the genes in the pathway had been identified. Now thirteen genes are known and there are strong indications that even more genes are involved. During his analysis of genetic material from FA patients, the researcher discovered one of the new genes that constitute part of the FA pathway. This gene, just like BRCA2, appears to be responsible for an increased risk of breast cancer.

The discovery of new genes enables researchers to gain a better understanding of how a defect in the FA pathway can cause cancer, even in people without FA. Ameziane's research has now revealed that a subtype of certain forms of cancer does indeed have a defect in the FA pathway. Ameziane discovered this whilst investigating tumour material from people without FA.

Although the role of genes in the FA pathway has not been fully clarified with this discovery, the discovery nevertheless gives hope for a more targeted approach to certain forms of cancer. That is because cells with a FA pathway defect are hypersensitive to certain drugs that are used during chemotherapy. Cancers that are caused by a FA defect can therefore be treated in a more targeted manner. Moreover, the study of the rare and incurable disease FA may provide insights into how cancer develops.

Najim Ameziane received a NWO Mosaic grant in 2004 for his PhD research. With this individual grant, NWO tries to encourage more people from ethnic minorities to carry out PhD research. Ameziane hopes to be able to continue his research as a post-doc.


Story Source:

The above story is based on materials provided by NWO (Netherlands Organization for Scientific Research). Note: Materials may be edited for content and length.


Cite This Page:

NWO (Netherlands Organization for Scientific Research). "New Target To Combat Cancer? Defects In Pathway Underlying Fanconi Anaemia Can Cause Cancer In Non-FA Patients." ScienceDaily. ScienceDaily, 20 May 2009. <www.sciencedaily.com/releases/2009/05/090514084119.htm>.
NWO (Netherlands Organization for Scientific Research). (2009, May 20). New Target To Combat Cancer? Defects In Pathway Underlying Fanconi Anaemia Can Cause Cancer In Non-FA Patients. ScienceDaily. Retrieved February 27, 2015 from www.sciencedaily.com/releases/2009/05/090514084119.htm
NWO (Netherlands Organization for Scientific Research). "New Target To Combat Cancer? Defects In Pathway Underlying Fanconi Anaemia Can Cause Cancer In Non-FA Patients." ScienceDaily. www.sciencedaily.com/releases/2009/05/090514084119.htm (accessed February 27, 2015).

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