Abstract: Aspects of the present disclosure are directed to immunotherapeutic methods for treating a subject having PDAC. Disclosed are methods comprising treatment with two or more immunotherapeutic agents for generating an effective immune response to PDAC. Certain aspects relate to methods comprising the use of a LAG-3 antagonist and a 41BB agonist, in some cases together with a chemokine receptor inhibitor, for the treatment of PDAC. Also disclosed are compositions comprising a LAG-3 antagonist and a 41BB agonist. In some cases the disclosed compositions further comprise a chemokine receptor inhibitor.

Abstract: The disclosure provides methods and compositions for treating subject having cancers with abnormal WNT signaling, such as APC-deficient cancers. Accordingly, aspects of the disclosure relate to methods for treating APC-deficient cancers comprising administering an inhibitor of TDO2 or of a cytokine activated by TDO2. Additional aspects relate to methods for identifying a cancer as being sensitive to TDO2 inhibition comprising detecting a deficiency in an APC gene and/or measuring an expression level of TDO2.

Abstract: The disclosure provides for methods and compositions for treating a premature aging disorder or neurodegenerative disorder, particularly neurodegenerative disorders associated with amyloid deposition and neuronal death, such as Alzheimer's disease. Accordingly, aspects of the disclosure relate to a method for treating a premature aging disorder in a subject in need thereof, comprising administering a TERT activating therapy to the subject. Further aspects relate to a method for treating a neurodegenerative disorder in a subject comprising administering a TERT activating therapy to the subject.

Abstract: Methods for reversing one or more mutations in the telomerase (TERT) promoter are provided and may be used to treat a cancer. In some embodiments, programmable base editing (PBE) is used to correct a mutated TERT promoter (e.g., ?124 C>T, ?228C>T, or ?250C>T to ?124 C, ?228C, or ?250C, respectively) by using a single guide (sg) RNA-guided and deactivated Campylobacter jejuni Cas9-fused adenine base editor (CjABE). These methods can be used to treat a cancer, such as for example glioblastoma multiforme (GBM), in a mammalian subject in vivo.

Abstract: The present invention provides a set of DETERMINANTS (e.g., genes and gene products) that can accurately inform about the risk of cancer progression and recurrence, as well as methods of their use.

Abstract: The present invention is based on the identification of novel biomarkers predictive of response to anti-cancer therapies.

Abstract: Provided herein are compounds of the formula (I) wherein the variables R1, R2, R3, R4, X1, X2, Y1, and A1 are as defined herein. Such compounds may be used, for example, for the inhibition of enolase enzymes, including preferential inhibition of one isoenzyme of over one or more of the other isoenzymes. Methods of treatment using these compounds, as well as pharmaceutical compositions thereof, are also provided.

Abstract: Provided herein are compounds of the formula (I) wherein the variables R1, R2, R3, R4, X1, X2, Y1, and A1 are as defined herein. Such compounds may be used, for example, for the inhibition of enolase enzymes, including preferential inhibition of one isoenzyme of over one or more of the other isoenzymes. Methods of treatment using these compounds, as well as pharmaceutical compositions thereof, are also provided.

Abstract: The subject matter relates to newly discovered nucleic acid molecules and proteins associated with thymic lymphoma and hamartomatous tumors. Compositions and methods for detecting, characterizing, preventing, and treating human thymic lymphoma and hamartomatous tumors are provided.

Abstract: Provided herein are compositions containing photoactivatable caged tamoxifen and tamoxifen derivative molecules. Also provided are kits containing one of these compositions and a light source. Also provided are methods of optically inducing nuclear translocation of a fusion protein containing a mammalian estrogen receptor ligand binding domain in a eukaryotic cell and methods of optically inducing recombination in a eukaryotic cell that include contacting a eukaryotic cell with at least one of these compositions. Also provided are methods of treating breast cancer in a subject that include administering a photoactivatable caged tamoxifen or tamoxifen derivative molecule to a subject having breast cancer.

Abstract: The present invention provides methods of detecting cancer using biomarkers.

Abstract: Methods for diagnosing and treating cancer associated with an oncogenic Kras mutation in a subject are provided.

Abstract: Provided herein are compositions containing photoactivatable caged tamoxifen and tamoxifen derivative molecules. Also provided are kits containing one of these compositions and a light source. Also provided are methods of optically inducing nuclear translocation of a fusion protein containing a mammalian estrogen receptor ligand binding domain in a eukaryotic cell and methods of optically inducing recombination in a eukaryotic cell that include contacting a eukaryotic cell with at least one of these compositions. Also provided are methods of treating breast cancer in a subject that include administering a photoactivatable caged tamoxifen or tamoxifen derivative molecule to a subject having breast cancer.

Abstract: The subject matter relates to newly discovered nucleic acid molecules and proteins associated with thymic lymphoma and hamartomatous tumors. Compositions and methods for detecting, characterizing, preventing, and treating human thymic lymphoma and hamartomatous tumors are provided.

Abstract: The present invention provides a set of DETERMINANTS (e.g., genes and gene products) that can accurately inform about the risk of cancer progression and recurrence, as well as methods of their use.

Abstract: The present invention provides a set of DETERMINANTS (e.g., genes and gene products) that can accurately inform about the risk of cancer progression and recurrence, as well as methods of their use.

Abstract: Methods for treating a subject determined to have a cancer comprising a heterozygous inactivation of a housekeeping gene (or a homozygous deletion of a functionally redundant housekeeping gene) by treating the subject with an inhibitor of the gene. For example, a subject having a cancer with an ENO gene deletion can be treated with a glycolysis inhibitor, such as an enolase inhibitor. In some aspects, a subject having a cancer with an ARS gene deletion can be treated with an ARS inhibitor.

Abstract: The invention relates to compositions, kits, and methods for detecting, characterizing, preventing, and treating human cancer. A variety of chromosomal regions (MCRs) and markers corresponding thereto, are provided, wherein alterations in the copy number of one or more of the MCRs and/or alterations in the amount, structure, and/or activity of one or more of the markers is correlated with the presence of cancer.

Abstract: Methods for diagnosing and treating cancer associated with an oncogenic Kras mutation in a subject are provided.

Abstract: The invention relates to compositions, kits, and methods for detecting, characterizing, preventing, and treating human pancreatic adenocarcinoma. A variety of chromosomal regions (MCRs) and markers in the MCRs, are provided that are correlated with cancer. In particular, chromosomal regions and markers in the MCR 50.06-62.89 Mb of human chromosome 19, are provided, wherein alterations in the copy number of the MCR and/or alterations in the amount, structure, and/or activity of one or more of the markers in the MCR is correlated with the presence of pancreatic adenocarcinoma.