University of Pittsburgh

Jianhua Luo

George Michalopoulos

Joel Byron Nelson

Chien-Cheng Tseng

Yanping Yu

Yangping Yu

Ying Ding

Zhanghui Chen

Chi Song

Shuchang Liu

George K Michalopoulos

The present invention relates to methods for treating patients having cancer or a premalignant or neoplastic condition. It is based, at least in part, on the discovery that a genome editing technique that specifically targets a fusion gene can induce cell death in a cancer cell other than a prostate cancer cell, e.g., a hepatocellular cancer cell, having the fusion gene. The present invention provides methods for treating cancer patients that include performing a genome editing technique targeting a fusion gene present within one or more cells of a subject to produce an anti-cancer effect.

Methods of treating cells containing fusion genes by genomic targeting

The present invention relates to methods of treating cancer patients carrying one or more specific fusion genes. It is based, at least in part, on the discovery that the protein encoded by the MAN2A1-FER fusion gene exhibits kinase activity and the use of tyrosine kinase inhibitors targeting MAN2A1-FER in a cancer other than prostate, for example hepatocellular cancer, led to dramatic improvement of survival of animals xenografted with the cancer.

Methods of treating cancers containing fusion genes

The present invention relates to methods for determining whether a subject having prostate cancer is at an increased risk for relapse or rapid relapse. It is based, at least in part, on the results of a comprehensive genome analysis of 273 prostate cancer samples, which indicate that the percentage of large size CNVs predicts prostate cancer relapse. In certain embodiments, a method for determining whether a prostate cancer patient has an increased risk of suffering a relapse or a rapid relapse comprises determining the number and size of CNVs in a sample and determining a large size ratio, where if the large size ratio exceeds a particular threshold, the patient is deemed to be at an increased risk for relapse or rapid relapse.

Methods for predicting prostate cancer relapse

The present invention relates to methods and compositions for determining whether a subject having prostate cancer is at greater risk of developing progressive disease, and methods of treating the subjects. It is based, at least in part, on the discovery that approximately 90% of men carrying at least one of the following fusion genes: TRMT11-GRIK2, SLC45A2-AMACR, MTOR-TP53BP1, LRRC59-FLJ60017, TMEM135-CCDC67 and CCNH-C5orf30 experienced prostate cancer recurrence, metastases and/or prostate cancer-specific death after radical prostatectomy (each examples of 'progressive prostate cancer'), while these outcomes occurred in only 36% of men not carrying any of these fusion genes. It is also based, at least in part, on the discovery that no patient studied survived five years without recurrence if their primary prostate cancer contained a TRMT11-GRIK2 or MTOR-TP53BP1 fusion gene. It is also based, at least in part, on the discovery that the protein encoded by the MAN2A1-FER fusion gene exhibits kinase activity.

Fusion genes associated with progressive prostate cancer

The present invention relates to methods for treating prostate cancer patients. It is based, at least in part, on the discovery that approximately 90% of men carrying at least one of the following fusion genes: TRMT11-GRIK2, SLC45A2-AMACR, MTOR-TP53BP1, LRRC59-FLJ60017, TMEM135-CCDC67 and CCNH-C5orf30 experienced prostate cancer recurrence, metastases and/or prostate cancer-specific death after radical prostatectomy (each examples of 'progressive prostate cancer'), while these outcomes occurred in only 36% of men not carrying any of these fusion genes. It is also based, at least in part, on the discovery that a genome editing technique that specifically targets a fusion gene can induce cell death in a cancer cell that carries the fusion gene.

Methods for treating cells containing fusion genes

The present invention relates to methods and compositions for diagnosing prostate cancer and/or determining whether a prostate cancer patient is at increased risk of suffering a relapse, or a rapid relapse, of his cancer. It is based, at least in part, on the results of a comprehensive genome analysis on 241 prostate cancer samples (104 prostate cancer, 85 matched bloods, 49 matched benign prostate tissues adjacent to cancer, and 3 cell lines) which indicate that (i) genome copy number variation (CNV) occurred in both cancer and non-cancer tissues, and (ii) CNV predicts prostate cancer progression.

Methods for diagnosing prostate cancer and predicting prostate cancer relapse

The present invention relates to methods and compositions for determining whether a subject having prostate cancer is at greater risk of developing progressive disease, and methods of treating the subjects. It is based, at least in part, on the discovery that approximately 90% of men carrying at least one of the following fusion genes: TRMT11-GRIK2, SLC45A2-AMACR, MTOR-TP53BP1, LRRC59-FLJ60017, TMEM135-CCDC67 and CCNH-05orf30 experienced prostate cancer recurrence, metastases and/or prostate cancer-specific death after radical prostatectomy (each examples of 'progressive prostate cancer'), while these outcomes occurred in only 36% of men not carrying any of these fusion genes. It is also based, at least in part, on the discovery that no patient studied survived five years without recurrence if their primary prostate cancer contained a TRMT11-GRIK2 or MTOR-TP53BP1 fusion gene. It is also based, at least in part, on the discovery that the protein encoded by the MAN2A1-FER fusion gene exhibits kinase activity.

The present invention relates to methods for treating prostate cancer patients. It is based, at least in part, on the discovery that approximately 90% of men carrying at least one of the following fusion genes: TRMT11-GRIK2, SLC45A2-AMACR, MTOR-TP53BP1, LRRC59-FLJ60017, TMEM135-CCDC67 and CCNH-05orf30 experienced prostate cancer recurrence, metastases and/or prostate cancer-specific death after radical prostatectomy (each examples of 'progressive prostate cancer'), while these outcomes occurred in only 36% of men not carrying any of these fusion genes. It is also based, at least in part, on the discovery that a genome editing technique that specifically targets a fusion gene can induce cell death in a cancer cell that carries the fusion gene.

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Wexford, PA, United States of America

Jianhua Luo