This Time It’s Personal: Tailoring cancer treatment to individual and evolving tumours

Lauren Gravitz in Scientific American:

CancerEvery cancer has a weak spot — a genetic vulnerability that could be exploited by the right drug — and many envision a day when the genome of every cancer will be sequenced, in full or in part, and then paired with an appropriate therapy. Researchers point to the effectiveness of imatinib (marketed as Gleevec and Glivec) against chronic myelogenous leukaemia (CML) — a rare blood cancer — as perhaps the greatest success in the personalized cancer field so far. CML is most often caused by an abnormal gene rearrangement in which pieces of two chromosomes switch places with each other. Assessing whether a patient is a candidate for the drug requires the analysis of a small group of genes in what is referred to as a gene panel. “In the 1980s, unless you got a bone-marrow transplant, the disease was an absolute death sentence in four to six years,” says Razelle Kurzrock, director of the Center for Personalized Cancer Therapy at the University of California, San Diego. “Today, average survival is more than 20 years. And because the average age at diagnosis is 60, it's almost a normal life expectancy.” That success comes at a price: in 2012, a year's worth of the therapy cost US$92,000. Imatinib's success has not been easy to duplicate. Every tumour has a unique set of genetic mutations — tumours are commonly likened to snowflakes, each is slightly different from the next. And this heterogeneity, which is found even between cells in a single tumour, means that matching a patient with the appropriate therapy can be a complex proposition.

Vulnerabilities such as the one that imatinib capitalizes on are known as driver oncogenes, genetic changes that generate the proteins driving a cancer's growth. Disabling these proteins should, at least in theory, beat back the disease. The number of driver oncogenes seems to be limited — perhaps as few as 200–300 common ones, says Robert Nussbaum, a medical geneticist at the University of California, San Francisco. Understanding how to disable the common driver oncogenes should therefore enable the treatment of a large number of cancers. “First, we have to know what the genes are and how are they mutating. Then, the second challenge is developing drugs that target these abnormally activated proteins,”

More here.