Study Finds Two New Methods for Small Cell Lung Cancer Therapy

Two novel methods to induce tumor cell death have been discovered by the authors of a new study performed on samples of small cell lung tumors (SCLC), published in Nature Communications. Because each of these methods targets 1 of 2 subtypes of tumor cell, both methods must be utilized simultaneously in order to kill the majority of the tumor mass, according to the study.

A diagnosis of SCLC carries a particularly poor prognosis, because at the time of diagnosis, the cancer has already found many ways to evade the immune system, according to the study. Regulated cell death by apoptosis is typically inactive by the time the cancer is detected, allowing cancer cells to divide and spread with little resistance.

SCLC cells can be divided into 2 categories: neuroendocrine cells and non-neuroendocrine cells. According to the study, non-neuroendocrine cells can be targeted by using buthionine sulfoximine and activating ferroptosis, which is iron-dependent cell death caused by oxidative stress.

Neuroendocrine cells protect themselves from oxidative stress through the production of antioxidants. For these cells, a secondary method utilizing the antioxidant inhibitor auranofin (Ridaura) is implemented in order to induce cell death, according to the study.

The researchers found that utilizing only 1 method at a time in a tumor consisting of both cell subtypes resulted in cancer cells evading therapy. The tumor cells accomplished this by adjusting their gene expression to switch to the subtype that could resist the respective single pathway-targeting treatment.

“When we applied a combination therapy, we took away this route of escape,” said Silvia von Karstedt, PhD, the study’s lead researcher, in a press release. “What is also special about the study is that we used drugs that have already been tested in extensive clinical trials or even approved for the treatment of other diseases.”

Buthionine sulfoximine is currently in clinical trials for cancer treatment, whereas auranofin has been in use for decades to treat rheumatoid arthritis. Further clinical studies utilizing this combined therapy will establish the extent to which this targeted therapy will improve the prognosis of patients with SCLC.

REFERENCE

Small cell lung cancer: Scientists identify two new approaches for therapy [news release]. EurekAlert; April 6, 2021. Accessed April 8, 2021. https://www.eurekalert.org/pub_releases/2021-04/uoc-scl040621.php