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Large-scale genetic study sheds new light on lung cancer
Date:10/22/2008

has tied RB1 mutations to retinoblastoma, a relatively uncommon type of childhood cancer that originates in the eye's retina.

  • Adenomatosis polyposis coli (APC). Mutations of this gene are common in colon cancer.

  • Ephrin receptors A3 and A5 (EPHA3 and EPHA5), neurotrophin receptors (NTRK1 and NTRK3) and other receptor-coupled tyrosine kinases (ERBB4, KDR and FGFR4). These genes code for cell receptors coupled to members of the tyrosine kinase family of enzymes, which are considered prime targets for new cancer therapies.

    After identifying the genetic mutations, the team went on to examine their impacts on biological pathways and determine which of those pathways were most crucial in lung adenocarcinoma. Such research is essential to efforts to develop new and better treatments for cancer.

    For example, TSP researchers found more than two-thirds of the 188 tumors studied had at least one gene mutation affecting the mitogen-activated protein kinase (MAPK) pathway, indicating it plays a pivotal role in lung cancer. Based on those findings, the researchers suggested new treatment strategies for some subtypes of lung adenocarcinoma might include compounds that affect the MAPK pathway. One such group of compounds, called MEK inhibitors, has produced promising results in mouse models of colon cancer.

    Likewise, the TSP's finding that more than 30 percent of tumors had mutations affecting the mammalian target of rapamycin (mTOR) pathway raises the possibility that the drug rapamycin might be tested in lung adenocarcinoma. Rapamycin is an mTOR-inhibiting compound approved for use in organ transplants and renal cancer.

    In addition, the genetic findings suggest that certain lung cancer patients might benefit from chemotherapy drugs currently used to treat other types of cancer. For example, chemotherapy drugs known to inhibit the kinase insert domain receptor (KDR), such as sorafenib and sunitinib, might be test
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  • Contact: Geoff Spencer
    spencerg@mail.nih.gov
    301-402-0911
    NIH/National Human Genome Research Institute
    Source:Eurekalert

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