The David H. Koch Institute for Integrative Cancer Research at MITThe David H. Koch Institute for Integrative Cancer Research at MIT

Massachusetts Institute of Technology

National Cancer Institute Cancer Center

Science + Engineering... Conquering Cancer Together

On the Origin of Mutations

You can take the tumor out of the tissue, but you can’t take the tissue out of the tumor. In a paper published in Science, the KI’s Vander Heiden Lab presents strong evidence that activation and suppression of cancer-causing genes can have wildly different results in cell metabolism depending on the tumor’s tissue of origin.

To prove that tissue of origin influences tumor behavior, researchers utilized models of both pancreatic ductal adenocarcinoma (PDAC) and non-small cell lung carcinoma (NSCLC) with identical genetic mutations. They found that despite having the same initiating events, the resulting cancer cells used branched-chain amino acids (BCAAs) differently as they proliferated. Their results showed that the NSCLC tumors used free-flowing BCAAs to supply the tumor with essential growth nutrients, while the PDAC tumors decreased their use of these free BCAAs. Indeed, blocking metabolism of these BCAAs inhibited the formation of NSCLC but not PDAC tumors. As such, they concluded that therapies designed to impair tumor growth by suppressing enzymes needed for BCAA use would be most effective in NSCLC and that a different treatment plan would be required to slow the growth of PDAC tumors.

The Vander Heiden Lab’s findings suggest a shifting paradigm for personalized medicine, in which context plays as critical a role as the genetic drivers. In other words, those who seek to exploit the pathways that cancer cells employ to survive ought to consider not just how the journey begins, but also where.