2024 World Conference on Lung Cancer (WCLC) - ePosters-EP.12B.07 Identification of Candidate Therapeutic Targets Using Single Cell RNA Sequencing in ALK-Positive Lung Cancers

EP.12B.07 Identification of Candidate Therapeutic Targets Using Single Cell RNA Sequencing in ALK-Positive Lung Cancers

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The study conducted by Marc A.T. Muskavitch and colleagues focuses on identifying potential therapeutic targets for ALK-positive lung cancers using single-cell RNA sequencing (scRNAseq). ALK fusion proteins are known for their oncogenic role in lung cancer, but they are not typically present on cell surfaces. This absence has hampered the development of surface-targeting therapies, such as antibody-drug conjugates (ADCs) and CAR-T cells, among others.<br /><br />The researchers developed a computational method to analyze publicly available scRNAseq data from lung cancer tumors, comparing these in particular with data from 107 healthy lung samples. The CellXGene VIP interface was used to visualize and assess gene expression across 61 lung cell types, aiming to discover positively expressed genes in cancer cells that could serve as potential therapeutic targets.<br /><br />The analysis categorized gene expression based on different patient subgroup percentages and identified several candidate genes corresponding to FDA-registered drug targets. These genes were found in various cell types, including AT2 cells—considered the origin of ALK lung cancers—and immune cells. Key targets identified include genes linked to ADCs, radioligands, and cancer vaccines.<br /><br />The study highlighted the expression of BNT116 vaccine targets, suggesting potential for clinical trials involving solid tumor vaccines for both ALK and EGFR lung cancer patients. The team aims to further validate their findings through acquiring additional tumor datasets and employing techniques like immunohistochemistry and mass spectrometry.<br /><br />Ultimately, the research underscores the potential of scRNAseq data in developing therapies that combine traditional and non-oncogene-targeted approaches to treat oncogene-driven cancers, with a future focus on leveraging immune checkpoint mechanisms to enhance immune-mediated tumor cell killing.

Asset Subtitle

Marc Muskavitch

Meta Tag

Speaker Marc Muskavitch

Topic Metastatic Non-small Cell Lung Cancer – Targeted Therapy

Keywords

ALK-positive lung cancer

single-cell RNA sequencing

therapeutic targets

oncogenic role

antibody-drug conjugates

CellXGene VIP

gene expression

FDA-registered drug targets

cancer vaccines

immune checkpoint mechanisms