Source BioScience is now able to offer a PI3Kinase test to help
select those patients with breast and colorectal cancers who are
most likely to benefit from anti-EGFR therapy
PI3K - Gene Mutation Analysis
The enzyme phosphoinositide 3-kinase (PI3K), product of
the PIK3CA gene, plays a key role in the cellular survival pathway,
one of two pathways activated by receptor tyrosine kinases such as
EGFR. Activating mutations of the PIK3CA gene are common in a
variety of cancers, including those of breast (27%) and colorectum
(19%). Recent studies suggest that such mutations are associated
with resistance to trastuzumab (Herceptin™), cetuximab (Erbitux™),
panitumumab (Vectibix™) and potentially lapatinib
(Tyverb/Tykerb™).
Source BioScience offers PI3K mutation testing based on two
alternative CE-marked technologies, both suitable for archival FFPE
tissue samples:
- The DxS PI3K Mutation Test uses real-time PCR to detect the 4
most common activating mutations occurring in exons 9 and 20 of the
PIK3CA gene
- Pyrosequencing using an assay developed and validated in-house
at Source Bioscience to evaluate a total of 9 mutations found in
exons 9 and 20
The results of mutation tests are reported as positive or
negative for the presence of a particular mutation, along with
additional information about relative frequencies of particular
mutations in colorectal and lung tumours.
References:
- Berns et al. (2007) A functional genetic approach identifies
the PI3K pathway as a major determinant of trastuzumab resistance
in breast cancer. Cancer Cell 12:395-402
- Sartore-Bianchi et al. (2009) PIK3CA mutations in colorectal
cancer are associated with clinical resistance to EGFR-targeted
monoclonal antibodies. Cancer Res 69:1851-7.
- Eichhorn et al. (2008) Phosphatidylinositol 3-kinase
hyperactivation results in lapatinib resistance that is reversed by
the mTOR/phosphatidylinositol 3-kinase inhibitor NVP-BEZ235. Cancer
Res 68:9221.