Abstract: Aspects of the present disclosure are directed to methods and compositions for diagnosing and/or treating a subject having cancer. Certain aspects relate to treatment with a cancer therapy and a YTHDF2 inhibitor or a pharmaceutical composition comprising a cancer therapy and a YTHDF2 inhibitor. In some aspects, the YTHDF2 inhibitor includes an oligonucleotide targeting YTHDF2 mRNA or a small molecule inhibitor of YTHDF2. In some aspects, a subject has been determined to have or to have had resistance to a previous cancer treatment, such as radiotherapy and/or immunotherapy.

Abstract: Methods, assays, and compositions for identifying molecular subtypes of metastatic cancer are disclosed. The disclosed methods include determining expression levels of genes in a sample of metastatic tissue and identifying the molecular subtype of the metastasis based on the determined expression levels using a neural network-based classifier. Methods may further include providing a prognosis and making a treatment decision based on the molecular subtype of the metastasis. Further disclosed are methods of treatment of a cancer subject with a particular cancer therapy (e.g., local therapy, immunotherapy, EGFR inhibitor therapy) based on a molecular subtype of a metastasis from the subject.

Abstract: Methods, assays, and compositions for identifying molecular subtypes of metastatic cancer are disclosed. Methods include determining expression levels of genes and/or miRNAs in a sample of metastatic tissue and identifying the molecular subtype of the metastasis based on the determined expression levels using a neural network-based classifier. Methods may further include providing a prognosis and making treatment decision based on the molecular subtype of the metastasis.