Novel Target Protein Discovered to Treat Small Cell Lung Cancer with Antibody-Drug Conjugates

Lung cancer 3D illustration and photo under microscope of histopathology light micrograph of small cell lung cancer

Researchers based out of Tokyo, Japan, recently experimented with testing new target mechanisms combined with antibody-drug conjugate (ADC) therapy to treat small cell lung cancer (SCLC). SCLC has maintained a relatively unimproved prognosis over the years and accounts for 10–15% of patients diagnosed with lung cancer.

Antibodies are proteins that can be used to target foreign agents, such as viruses or bacteria, and other mechanisms in the body in need of regulation. ADC therapies work by adjoining antibodies with toxic agents. The ADCs are created to first, precisely pinpoint cancerous tumors using specially designed antibodies and then, to release cytotoxins delivering the tumor cells with a pharmaceutical drug that is thousands of times more potent than chemotherapy (without damaging the healthy cells nearby). 

“We searched for transmembrane proteins of SCLC using a computational-biological approach. […] We identified transmembrane proteins overexpressed specifically in SCLC, with little or no expression in normal tissues, and decided to focus on the cell adhesion molecule neurexin-1 (NRXN1).”

Transmembrane proteins stretch along the outside of the entire cell and are the gatekeepers that dictate what goes in or out of the cell. In the in vitro study, researchers combined commercially available anti-NRXN1 antibodies with a secondary antibody-drug conjugate. The expression of the NRXN1 protein was analyzed using two SCLC cell lines. They found the results of this experiment exhibited anti-tumor growth activity in the SHP77 cell line in small cell lung cancer.

“We herein report that NRXN1-mediated ADC exhibited anti-tumor activity in vitro, and thus NRXN1 could be a novel target of ADCs for SCLC.”

Though NRXN1 is limited in the central nervous system, the paper does indicate possible central nervous system side effects and suggests that it be further investigated in future in vivo experiments.

Oncotarget is a unique platform designed to house scientific studies in a journal format that is available for anyone to read – without a paywall making access more difficult. This means information that has the potential to benefit our societies from the inside out can be shared with friends, neighbors, colleagues and other researchers, far and wide.

Click here to read the full scientific paper, published in Oncotarget.

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