Enhancement of melanoma chemosensitivity by adenoviral delivery of PUMA

Melanoma is an aggressive and lethal form of skin cancer that is increasingly prevalent among Caucasians. Although often curable if diagnosed early and surgically removed, melanoma tumors can rapidly metastasize (spread) to other parts of the body. Patients diagnosed with melanoma at later stages face a poor prognosis and survival rates averaging only six to ten months. Once it has spread, melanoma is extremely difficult to treat because it does not respond well to conventional cancer treatments such as radiation and chemotherapy. But the reason for this resistance is unknown. Most anti-cancer drugs induce apoptosis (programmed cell death) in tumor cells. Melanoma may have abnormally high levels of cell survival genes, making them difficult to kill with such drugs. Alison Karst is investigating whether introduction of the PUMA cell death gene into malignant tumors could overcome this problem and sensitize malignant cells to chemotherapy.