Novel Oncogenic RET Mutation Found in Small Cell Lung Cancer

Editor’s note: An oncologist will sometimes test a patient’s tumor for specific mutations in order to decide what the best treatment options are. Tumors that have certain mutations can sometimes be treated with certain so-called targeted therapy drugs. This approach has worked well for many people with non-small cell lung cancer (NSCLC). However, there are no FDA-approved targeted therapies for small cell lung cancer (SCLC). A new discovery might change that. Researchers found a mutation called RET M918T in a metastatic SCLC tumor. Two targeted drugs were found to fight against tumor cells with the mutation in the lab. The drugs—ponatinib and vandetanib—are already FDA-approved to treat other types of cancer.

“For the first time, an oncogenic somatic mutation at amino acid 918 in the rearranged during transfection protein has been identified in small cell lung cancer tumors and enforced expression of this mutation within small cell lung cancer tumor cell lines produced increased intracellular signaling and cell growth.

“SCLC is a highly malignant form of lung cancer representing 15% of all lung cancers and is strongly associated with tobacco smoking. NSCLC, representing 85% of lung cancer, has been extensively examined for genomic alterations and targeted therapies are approved for patients with certain mutations, however SCLC has not been examined with the same rigor and there are no approved targeted therapies for SCLC.

“Investigators at Case Western University examined 6 SCLC tumors, 3 each from primary and metastatic tumors, for 238 somatic mutations across 19 oncogenes. RET wild type and mutant protein was then overexpressed in SCLC cell lines and these cell lines were examined for cell signaling, cell growth and responsiveness to two tyrosine kinase inhibitors of RET.”


Thoracic RT Yields Improved Survival in Extensive-Stage SCLC

“Thoracic radiotherapy along with prophylactic cranial irradiation (PCI) significantly prolonged progression-free and overall survival in patients with extensive-stage small-cell lung cancer, according to results of a new study presented at ASCO.

“Ben Slotman, MD, PhD, of VU University Medical Center in Amsterdam, presented the study and said that previous work had shown that PCI could improve both symptomatic brain metastases and overall survival at 1 year. ‘In that study, we also noticed that the vast majority of patients after chemotherapy had intrathoracic disease’ and intrathoracic progression, he said, which was the impetus for the new study using thoracic radiotherapy.”

Editor’s note: To learn more about new prospects for treating small cell lung cancer (SCLC), see our two-part blog feature on the topic.