Crizotinib, recently approved by the FDA as Xalkori by Pfizer, is a great example of the concept of picking chemotherapy that is specific to an individual person’s cancer. As the physician whose wife is fighting ovarian cancer I have been following the progress in various cancer therapies with hope for major breakthroughs in cancer treatment. Personalized therapy for cancer is a work in progress, but crizotinib seems to be a good example of a drug where patients can be tested to see whether the drug is likely to work for their cancer.
The theory of testing cancer cells to see what drugs will be most effective is somewhat like the way we test the bacteria causing an infection to see what antibiotics work well to kill the specific strain of germ causing an individual patient’s infection. Bacteria are collected from the infection site and lab testing is done to see which antibiotics are most effective in killing those bacteria. Crizotinib is a chemotherapy agent that is an inhibitor of the enzyme anaplastic lymphoma kinase (ALK). Approved for use at the same time as crizotinib was a test called Vysis ALK Break Apart FISH Kit, made by Abbott molecular, that can be used to test the cancer cells to see if they express this specific enzyme. If a patient with non-small cell lung cancer has cancer cells that express this specific enzyme, then crizotinib may be useful in targeting the cancer cells in those patient. It would not likely be useful in patients where the cancer cells do not express the ALK enzyme.
Crizotinib is approved for treatment of advanced non-small cell lung cancer that expresses the ALK enzyme. The concept of choosing cancer treatments based specifically for an individual based on the characteristics of their cancer cells is very much in vogue and there is a good deal of hope for this type of therapy. An example of this type of therapy is the use of PARP inhibitors in breast and ovarian cancer patients who have the BRCA gene mutations. The theory in these BRCA 2 mutation positive patients is that since they lack the function of the BRCA gene that helps repair double stranded DNA breaks that inhibiting the PARP function that repairs single stranded DNA breaks will make cancer cells more susceptible to chemotherapy agents or the body’s own immune system. Although this is somewhat less targeted than the crizotimib approach it is theoretically somewhat patient specific therapy.
In breast cancer patients testing the cancer cells for estrogen receptor status, and targeting estrogen receptor positive tumors for anti-estrogen therapy with tamoxifen and other drugs has been standard therapy for years. New immunotherapy and antibody based therapies are also patient and tumor specific therapies. The ideal of using chemotherapy targeted specifically at an individual’s cancer cells rather that lumping all patients with a given type of cancer into the same regimens of treatment is unique and seems to hold much promise. Time will tell just how helpful crizotinib is for advanced non-small cell lung cancers that express the ALK gene, but this type of treatment where more specific therapy is targeted at an individual’s cancer cells is exciting and promising.
Although crizotinib is going to be targeted at a fairly small cohort of patients it is exciting to see the progress of personalized cancer therapy take one more step forward.