Abstract: The invention provides methods of inhibiting the growth or metastasis of a cancer in a mammal by inhibiting a Ral GTPase in the mammal. The invention also provides small molecule inhibitors of Ral GTPases useful in the methods of the invention and pharmaceutical compositions containing the therapeutically effective compounds of the invention, and methods of using the same.

Abstract: We combined single nuclei RNA sequencing with spatial transcriptomics and single-cell resolution spatial proteomic analysis of human bladder cancer to identify an epithelial subpopulation with therapeutic response prediction ability. These cells express Cadherin 12 (CDH12, N-Cadherin 2), catenins, and other epithelial markers. CDH12-enriched tumors define patients with poor outcome following surgery with or without neoadjuvant chemotherapy (NAC), whereas CDH12-enriched tumors have a superior response to immune checkpoint therapy (ICT). Patient stratification by tumor CDH12 enrichment offered better prediction outcome than established bladder cancer subtypes. The CDH12 population resembles an undifferentiated state with chemoresistance. CDH12-enriched cells express PD-L1 and PD-L2 and co-localize with exhausted T-cells, possibly mediated through CD49a (ITGA1), likely explaining ICT efficacy in these tumors.

Abstract: Embodiments of the instant disclosure relate to novel methods and compositions for treating tumors resistant to platinum-based chemotherapy. In certain embodiments, methods of treating tumors herein can include administering an effective amount of at least one M1 aminopeptidase inhibitor in combination with at least one platinum-based chemotherapeutic agent separately or in a combination therapy. In some embodiments, methods of treating tumors disclosed herein can include screening and/or selecting a subject suitable for treatment based on NPEPPS gene or protein expression in the tumor to be treated. In other embodiments, methods of treating tumors can include administering a composition including a combination of at least one M1 aminopeptidase inhibitor and at least one platinum-based chemotherapeutic agent. In certain embodiments, compositions disclosed herein can include at least tosedostat and carboplatin.

Abstract: The present invention describes methods of detecting biomarkers in tumor tissue, as well as methods of improving responsiveness to or providing survival prognosis for a subject having received or in need of, an immune checkpoint inhibitor in the treatment of cancers such as bladder cancer, lung cancer, leukemia. Discoidin domain receptor (DDR)-driven gene signatures have been identified and validated to stratify patient response to anti-PD-L1 immune checkpoint therapy.

Abstract: Methods of inhibiting the growth or metastasis of a cancer in a subject by inhibiting a Ral GTPase in the subject, and small molecule inhibitors of Ral GTPases useful in the methods of the invention. Pharmaceutical compositions containing the compounds of the invention, and methods of using the same.

Abstract: Provided herein, in some embodiments, are methods and compositions for gene editing using a trackable gene library, for example, a barcoded and gene edited library.

Abstract: The invention provides methods of inhibiting the growth or metastasis of a cancer in a mammal by inhibiting a Ral GTPase in the mammal. The invention also provides small molecule inhibitors of Ral GTPases useful in the methods of the invention and pharmaceutical compositions containing the therapeutically effective compounds of the invention, and methods of using the same.

Abstract: Methods of inhibiting the growth or metastasis of a cancer in a subject by inhibiting a Ral GTPase in the subject, and small molecule inhibitors of Ral GTPases useful in the methods of the invention. Pharmaceutical compositions containing the compounds of the invention, and methods of using the same.

Abstract: The invention provides methods of inhibiting the growth or metastasis of a cancer in a mammal by inhibiting a Ral GTPase in the mammal. The invention also provides small molecule inhibitors of Ral GTPases useful in the methods of the invention and pharmaceutical compositions containing the therapeutically effective compounds of the invention, and methods of using the same.

Abstract: Methods of inhibiting the growth or metastasis of a cancer in a subject by inhibiting a Ral GTPase in the subject, and small molecule inhibitors of Ral GTPases useful in the methods of the invention. Pharmaceutical compositions containing the compounds of the invention, and methods of using the same.

Abstract: Methods of inhibiting the growth or metastasis of a cancer in a subject by inhibiting a Ral GTPase in the subject, and small molecule inhibitors of Ral GTPases useful in the methods of the invention. Pharmaceutical compositions containing the compounds of the invention, and methods of using the same.

Abstract: Methods of inhibiting the growth or metastasis of a cancer in a subject by inhibiting a Ral GTPase in the subject, and small molecule inhibitors of Ral GTPases useful in the methods of the invention. Pharmaceutical compositions containing the compounds of the invention, and methods of using the same.

Abstract: Methods of inhibiting the growth or metastasis of a cancer in a subject by inhibiting a Ral GTPase in the subject, and small molecule inhibitors of Ral GTPases useful in the methods of the invention. Pharmaceutical compositions containing the compounds of the invention, and methods of using the same.

Abstract: Disclosed are biomarkers, methods and assay systems for the identification of cancer patients who are predicted to respond, or not respond to the therapeutic administration of radiation therapy to treat cancer. Thus, the invention provides a diagnostic paradigm to select cancer patients who will benefit from radiation therapy. In particular, the invention provides a novel 41-gene biomarker model associated with clinical outcome following radiotherapy across multiple histological tumor types, including the biomarker Cyclophilin B (PPIB).

Abstract: The invention provides methods of inhibiting the growth or metastasis of a cancer in a mammal by inhibiting a Ral GTPase in the mammal. The invention also provides small molecule inhibitors of Ral GTPases useful in the methods of the invention and pharmaceutical compositions containing the therapeutically effective compounds of the invention, and methods of using the same.

Abstract: The invention provides methods of inhibiting the growth or metastasis of a cancer in a mammal by inhibiting a Ral GTPase in the mammal. The invention also provides small molecule inhibitors of Ral GTPases useful in the methods of the invention and pharmaceutical compositions containing the therapeutically effective compounds of the invention, and methods of using the same.

Abstract: The present invention relates to identification of a transcriptional signature of RalA and RalB GTPase proteins that is present in human cancer cells, and methods of treating the cancer, methods of diagnosis of the cancer, methods of determining predisposition to the cancer, methods of monitoring progression/regression of the cancer, methods of assessing efficacy of compositions for treating the cancer, methods of screening compositions for activity in modulating biomarker of the cancer, as well as other methods and assay systems based on the signature.

Abstract: Disclosed are biomarkers, methods and assay systems for the identification of cancer patients who are predicted to respond, or not respond to the therapeutic administration of radiation therapy to treat cancer. Thus, the invention provides a diagnostic paradigm to select cancer patients who will benefit from radiation therapy. In particular, the invention provides a novel 41-gene biomarker model associated with clinical outcome following radiotherapy across multiple histological tumor types, including the biomarker Cyclophilin B (PPIB).

Abstract: The invention provides methods of inhibiting the growth or metastasis of a cancer in a mammal by inhibiting a Ral GTPase in the mammal. The invention also provides small molecule inhibitors of Ral GTPases useful in the methods of the invention and pharmaceutical compositions containing the therapeutically effective compounds of the invention, and methods of using the same.

Abstract: Methods of inhibiting the growth or metastasis of a cancer in a subject by inhibiting a Ral GTPase in the subject, and small molecule inhibitors of Ral GTPases useful in the methods of the invention. Pharmaceutical compositions containing the compounds of the invention, and methods of using the same.