Cancer Mutations and Personalized Therapy

Recently published research has led some observers to say there is a revolution in treatment of cancer underway. While the scientific findings directly affect only a fraction of patients with specific mutations, it is great news for the field of cancer research overall as it points the way toward better and more efficient treatments. Scientists are looking forward to an era of personalized therapy for cancer patients.

Also called precision medicine, this paradigm involves doctors choosing treatment regimens based on genetic sequencing of each patient’s cancer. Sometimes experiments are done on tissue removed from the cancer patients – it’s like a little clinical trial on just one patient. 

One of the keys to personalized therapy is rapid DNA sequencing. Scientists have developed computer models of several types of cancer in recent years, including lung cancer, leukemia, and breast cancer. The ability to determine which tumors have specific mutations and then test those cancers against drugs lets scientists figure out which drugs best treat which types of cancer. So while in the past, all adenocarcinoma of the lung cancer patients at the same stage might have been given the same treatment, in the future, patients will get treatments that depend on the genotype of their cancer.

The new approach means good news for cancer patients, doctors and drug manufacturers. Clinical trials for targeted therapy drugs often require fewer test subjects and can be conducted at a much lower cost. The speed and efficiency of these trials allows doctors to obtain drugs faster and helps patients affected by a particular type of cancer with a peculiar biomarker can get the drugs that they need to survive that much sooner.

Researchers and clinicians refer to these mutations by acronyms typically of 3 to 5 characters. For instance epidermal growth factor receptor is referred to as EGFR, a mutation of this gene is of interest to lung cancer researchers. HER2 stands for human epidermal growth factor receptor 2 and it is a marker for some breast cancers.  Researchers at MD Anderson have proposed a Bayesian technique for efficiently choosing treatment.

Three quarters of lung cancer patients with EGFR-activating mutations respond well to the chemotherapy drug gefitinib. EGFR is a protein that cells produce and improper activation can lead to uncontrolled cell division and cancer The ALK mutation has been shown to respond to crizotinib in testing. A testing method for determining which patients have this mutation should be available soon.

A presentation at the 2011 American Society of Clinical Oncology reported that non-small cell lung cancer patients who took crizotinib along with their regular chemotherapy treatments saw their tumors reduced and survived four times as long as those on conventional chemotherapy alone.

 

The National Cancer Institute has created the Lung Cancer Mutation Consortium of 14 major cancer research and treatment centers across the country. The consortium is a coordinated effort to find a quick assay for identification of tumor mutations including KRAS, HER2, BRAF, PIK3CA, AKTI, MEKI, NRAS, and MET.

Drug researchers are already working on compounds that will treat cancer with these mutations in various cancers. The HER2 mutation is already a target of two breast cancer drugs on the market.

Early results show that show that 54% of the tumors tested under consortium auspices have single-driver mutations. Tumors with only one mutation may turn out to be more amenable to treatment. The Lung Cancer Mutation Consortium is running a large study of 1000 adenocarcinoma of the lung patients for mutations.

There are skeptics who point out that even when a patient’s cancer is sequenced, doctors are not usually able to pair the patient with a regimen that does significantly better than the old-style treatment.

Other scientists look to a future of personalized therapy in which the chemotherapy regimen is chosen based partly on genetic tests of the tumor. This change has been made possible partly by technological advances in genome sequencing. Using therapies that are known to be effective against specific mutations, doctors can raise the odds of success. The one-size-fits all treatment, which does not take into account the tumor mutation, is most often used today, but if this revolution goes forward as many suspect, it will be seen in the future as primitive.

See also: adaptive chemotherapy