PARP Inhibitors and Immunotherapy

FOR THE FIRST TIME in decades, new generations of cancer drugs — PARP inhibitors and immunotherapy — are leading to practice-changing techniques in small cell lung cancer. Researchers in the field are excited to examine how both translate to survival outcomes for patients, and so far, results have been positive.

New discoveries show that the two approaches go hand in hand and may one day lead to co-targeting or a combination of PARP inhibitors and immunotherapy to treat small cell lung cancer. Research has found that in many cases of small cell cancer, patients have abnormalities in DNA repair ability, which is tied to immune therapy: Tumors deficient in DNA repair tend to have more mutations because they can’t repair their DNA. More mutations means there are also more abnormal proteins that are recognizable by the immune system, which may interpret them as being foreign.

Immunotherapy drugs might then work more effectively to fight the DNA repair—deficient cancer cells. Adding a PARP inhibitor could theoretically help kill cancer cells if the drug prevents the cells from repairing the damaged DNA. This idea of combining the two has been studied in other cancer types, such as breast cancer, which showed some of the highest responses seen with immunotherapy in the disease. Currently, the Food and Drug Administration has approved only one type of immunotherapy for small cell lung cancer, Opdivo (nivolumab), and no PARP inhibitors.

Historically, small cell lung cancer has been difficult to treat with chemotherapy. Although tumors initially shrink, the cancer often comes back aggressively.

And this goes along with DNA damage response. DNA instability, repair instability and genomic diversity go together, making cancer cells more sensitive to chemotherapy but also more likely to harbor resistant cells that could come roaring back — something seen in small cell lung cancer.

In CURE®’s cover story, patient stories reveal just how much these newer approaches are not only extending their lives but also increasing their quality of life. This research shows how taking something that has been known for decades can be turned into cutting-edge advances in a disease that once had little hope.

DEBU TRIPATHY, M.D.Editor-in-ChiefProfessor of MedicineChair, Department of Breast Medical OncologyThe University of Texas MD Anderson Cancer Center