Genomic Profiles May Improve NSCLC Treatment
Stage IA NSCLC is before the cancer has metastasized and is usually treated with surgery alone. Many stage I NSCLC patients do not benefit from chemotherapy. However, the cancer recurs in a third of patients in this group. Patients found to have an increased risk for recurrence could be offered chemotherapy to help reduce their chance of recurrence.
Our research shows that the cancers that recur and the ones that do not have different genomic profiles. We are working to develop a genomic profile that doctors can use to identify patients whose cancer is more likely to recur. Patients with an increased risk for recurrence could be offered chemotherapy to reduce the chance of their cancer coming back.
NSCLC in stages IB, II, or IIIA are usually treated with surgery followed by chemotherapy. Not all stage IB tumors are treated with chemotherapy and stage IIIA tumors often also receive radiation therapy. Chemotherapy received after surgery is called adjuvant chemotherapy.
From basic research we think that patients with NSCLC stage IB, II, or IIIA may benefit from drugs called targeted therapy before and after surgery. Dasatinib is one such agent that is targeted toward a specific part of the cancer cell. It works by interfering with a part of the cell that is overactive in many lung cancers.
Adjuvant chemotherapy is of proven benefit in stage II and IIIA NSCLC. Early research suggests it may also be of benefit in some patients with stage IB NSCLC. We are working to develop genomic profiles that doctors could use to identify patients who may benefit from targeted therapy. Another set of genomic profiles could help doctors identify patients that may benefit from specific chemotherapy combinations after surgery rather than chemotherapy combinations that are not specifically selected to be active against a given tumor. In this way, genomic profiles would help the doctor provide each patient with a combination of treatment that is most likely to benefit him or her.
Advanced NSCLC (Stage IV) is usually treated with a combination of two types of chemotherapy, called a doublet. Stage IV treatment may combine a platinum based agent and a different type of drug, or non-platinum doublet or single chemotherapy drug.
Unfortunately, platinum based chemotherapy only helps a third of Stage IV patients. Another genomic profile we are developing may help doctors identify patients whose cancer will probably not respond to platinum-based treatment. By knowing beforehand which patients are unlikely to be helped by platinum chemotherapy, these patients can receive the most appropriate chemotherapy treatment from the start.
Using a tumor's genomic profile as a guide to selecting cancer treatment will be part of "personalized medicine." With personalized medicine, a doctor chooses an individualized treatment program for a patient based on genomic information from the patient's tumor. Think of the genomic profile of a lung cancer tumor as another tool in the physician's kit.
Genomic profiles allow us to compare how types of tumors use genes differently. Different genes may be turned on or off, or operating differently in various types of tumors. The activity of genes in a tumor's cells changes its behavior, a bit like varying a cake's ingredients changes its flavor and appearance. We can use these differences to learn more about how to treat patients with different types and stages of NSCLC.
We can compare and study genomic profiles from different NSCLC tumors to answer important questions.
- Why are some early stage tumors more likely to recur than others?
- Why are some tumors sensitive to platinum based chemotherapy while others are not?
- What distinguishes tumors that need to be treated with platinum based chemotherapy from tumors that need treatment with other chemotherapy agents?
- What characterizes tumors that respond to treatment with targeted therapies?
Once we know more about why tumors behave differently, we hope to be able to use this knowledge to select the best existing treatment or design new treatments.