PARP Inhibitor Promising Treatment for Small Cell Lung Cancer
by C.H. Weaver M.D. 8/23/2018
The results of a recent study published in The Journal of Clinical Oncology suggest the first new therapeutic option for Small Cell Lung Cancer (SCLC) in many years. The study evaluated the addition of a novel precision cancer medicine called a PARP inhibitor to standard chemotherapy improved overall response rates and delayed cancer progression in patients with advanced SCLC.
About Small Cell Lung Cancer
According to the American Cancer Society, more than 234,000 people will be diagnosed with lung cancer and 154,050 will die from the disease in 2018, making it the leading cause of cancer death. SCLC primarily is associated with smoking and accounts for about 10 to 15 percent of all lung cancers. The survival for most SCLC patients is less than a year and there have been no recent advances in its treatment.
About PARP Inhibitors
Not all cancer cells are alike: Cancer cells may differ from one another based on what genes have mutations. Precision cancer medicine utilizes molecular diagnostic testing, including DNA sequencing, to identify cancer-driving abnormalities in a cancer’s genome. This “genomic testing” is performed on a biopsy sample of the cancer and increasingly in the blood using a “liquid biopsy”
Once a genetic abnormality is identified, a specific precision cancer medicine or targeted therapy can be designed to attack a specific mutation or other cancer-related change in the DNA programming of the cancer cells. Precision cancer medicine uses targeted drugs and immunotherapies engineered to directly attack the cancer cells with specific abnormalities, leaving normal cells largely unharmed.
The poly ADP-ribose polymerase (PARP) enzyme plays a role in DNA repair, including the repair of DNA damage from chemotherapy. Precision cancer medicines that target and inhibit this enzyme may contribute to cancer cell death and increased sensitivity to chemotherapy and are called PARP inhibitors. By blocking this enzyme, DNA inside the cancerous cells is less likely to be repaired, leading to cell death and possibly a slow-down or stoppage of tumor growth.
In the current study doctors from MD Anderson Cancer Center enrolled 104 patients with relapsed SCLC from seven centers across the country. Patients were treated with either the PARP inhibitor veliparib combined with a standard oral chemotherapy regimen or the chemotherapy alone and directly compared.
Overall the combination therapy was well tolerated, and the researchers found that, the overall response to treatment was almost was three times higher in patients treated with the PARP inhibitor plus chemotherapy compared to chemotherapy alone.
Researchers also investigated biomarkers that might predict a response to PARP inhibitors and found that patients whose tumors expressed the elevated levels of SLFN11 experienced significantly delayed cancer progression and improved survival.
The doctors are now further evaluating PARP inhibitors as initial treatment and in higher doses. Advances in identifying precision cancer medicines have recently improved the outcomes in many kinds of cancer and now perhaps these advances will benefit individuals with SCLC.