Abstract: Aspects of the disclosure are directed to methods and systems for diagnosis, classification, and treatment of small cell lung cancer and high grade neuroendocrine carcinomas. Certain aspects comprise detection and analysis of tumor DNA methylation. Included in the disclosure are methods for identifying a subject as having a particular small cell lung cancer subtype based on DNA N methylation analysis, as well as methods and compositions for treatment of a subject based on subtype classification.

Abstract: The current disclosure provides novel therapeutic methods for treating SCLC and other neuroendocrine cancers by evaluating the biomarker SLFN11. Aspects of the disclosure relate to a method for treating a subject with small cell lung cancer (SCLC) or with a neuroendocrine cancer, the method comprising administering a combination of lurbinectedin and an ATR inhibitor to a subject that has had been determined to be negative for SLFN11 expression or have low SLFN11 expression in a biological sample from the subject.

Abstract: Provided herein are methods for determining a subtype of a small cell lung cancer in a patient based on the express status of ASCL1, NEUROD1, and POU2F3, which are expressed in a mutually exclusive fashion. The subtype of the cancer can be used to determine the sensitivity of the cancer to certain anti-cancer therapies. As such, also provided are methods of treating patients having small cell lung cancer based on the subtyping results.

Abstract: Aspects of the present disclosure are directed to methods for classification and treatment of small cell lung cancer (SCLC). Certain aspects pertain to treatment of a subject having SCLC using a targeting agent for a cell surface protein, where a targeting agent is selected based on a subtype classification of the SCLC. Disclosed are methods for identifying a subject as having an SCLC subtype (e.g., SCLC-A, SCLC-N, SCLC-P, SCLC-I) and administering a targeting agent configured to target a cell surface protein associated with the identified SCLC subtype. Also disclosed are compositions comprising targeting agents for treatment of SCLC.

Abstract: Provided herein are methods for determining a subtype of a small cell lung cancer in a patient based on the express status of ASCL1, NEUROD1, and POU2F3, which are expressed in a mutually exclusive fashion. The subtype of the cancer can be used to determine the sensitivity of the cancer to certain anti-cancer therapies. As such, also provided are methods of treating patients having small cell lung cancer based on the subtyping results.

Abstract: Provided herein are methods for determining a subtype of a small cell lung cancer in a patient based on the express status of ASCL1, NEUROD1, and POU2F3, which are expressed in a mutually exclusive fashion. The subtype of the cancer can be used to determine the sensitivity of the cancer to certain anti-cancer therapies. As such, also provided are methods of treating patients having small cell lung cancer based on the subtyping results.