1. Nuclear PTEN tumor-suppressor functions through maintaining heterochromatin structure.

    Cell Cycle 14(14):2323 (2015) PMID 25946202

    The tumor suppressor, PTEN, is one of the most commonly mutated genes in cancer. Recently, PTEN has been shown to localize in the nucleus and is required to maintain genomic stability. Here, we show that nuclear PTEN, independent of its phosphatase activity, is essential for maintaining heteroch...
  2. ARID1A Deficiency Impairs the DNA Damage Checkpoint and Sensitizes Cells to PARP Inhibitors.

    Cancer Discovery 5(7):752 (2015) PMID 26069190 PMCID PMC4497871

    ARID1A, SWI/SNF chromatin remodeling complex subunit, is a recently identified tumor suppressor that is mutated in a broad spectrum of human cancers. Thus, it is of fundamental clinical importance to understand its molecular functions and determine whether ARID1A deficiency can be exploited ther...
  3. A decision support framework for genomically informed investigational cancer therapy.

    JNCI Journal of the National Cancer Institute 107(7) (2015) PMID 25863335

    Rapidly improving understanding of molecular oncology, emerging novel therapeutics, and increasingly available and affordable next-generation sequencing have created an opportunity for delivering genomically informed personalized cancer therapy. However, to implement genomically informed therapy...
  4. Association of Somatic Mutations of ADAMTS Genes With Chemotherapy Sensitivity and Survival in High-Grade Serous Ovarian Carcinoma.

    JAMA Oncology 1(4):486 (2015) PMID 26181259

    Chemotherapy response in the majority of patients with ovarian cancer remains unpredictable. To identify novel molecular markers for predicting chemotherapy response in patients with ovarian cancer. Observational study of genomics and clinical data of high-grade serous ovarian cancer cases with ...
  5. Death-associated protein kinase 1 promotes growth of p53-mutant cancers.

    Journal of Clinical Investigation 125(7):2707 (2015) PMID 26075823

    Estrogen receptor-negative (ER-negative) breast cancers are extremely aggressive and associated with poor prognosis. In particular, effective treatment strategies are limited for patients diagnosed with triple receptor-negative breast cancer (TNBC), which also carries the worst prognosis of all ...
  6. Genomic Correlate of Exceptional Erlotinib Response in Head and Neck Squamous Cell Carcinoma.

    JAMA Oncology 1(2):238 (2015) PMID 26181029

    Randomized clinical trials demonstrate no benefit for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in unselected patients with head and neck squamous cell carcinoma (HNSCC). However, a patient with stage IVA HNSCC received 13 days of neoadjuvant erlotinib and experienced a ...
  7. Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer.

    Clinical Cancer Research 21(7):1688 (2015) PMID 25208879 PMCID PMC4362882

    Genomic profiling studies suggest that triple-negative breast cancer (TNBC) is a heterogeneous disease. In this study, we sought to define TNBC subtypes and identify subtype-specific markers and targets. RNA and DNA profiling analyses were conducted on 198 TNBC tumors [estrogen receptor (ER) neg...
  8. Co-clinical assessment identifies patterns of BRAF inhibitor resistance in melanoma.

    Journal of Clinical Investigation 125(4):1459 (2015) PMID 25705882 PMCID PMC4396463

    Multiple mechanisms have been described that confer BRAF inhibitor resistance to melanomas, yet the basis of this resistance remains undefined in a sizable portion of patient samples. Here, we characterized samples from a set of patients with melanoma that included individuals at baseline diagno...
  9. Development of a robust classifier for quality control of reverse-phase protein arrays.

    PMID 25380958 PMCID PMC4375399

    High-throughput reverse-phase protein array (RPPA) technology allows for the parallel measurement of protein expression levels in approximately 1000 samples. However, the many steps required in the complex protocol (sample lysate preparation, slide printing, hybridization, washing and amplified ...
  10. Genetic events that limit the efficacy of MEK and RTK inhibitor therapies in a mouse model of KRAS-driven pancreatic cancer.

    Cancer Research 75(6):1091 (2015) PMID 25736685 PMCID PMC4446709

    Mutated KRAS (KRAS*) is a fundamental driver in the majority of pancreatic ductal adenocarcinomas (PDAC). Using an inducible mouse model of KRAS*-driven PDAC, we compared KRAS* genetic extinction with pharmacologic inhibition of MEK1 in tumor spheres and in vivo. KRAS* ablation blocked prolifera...
  11. Genetic Events That Limit the Efficacy of MEK and RTK Inhibitor Therapies in a Mouse Model of KRAS-Driven Pancreatic Cancer.

    Cancer Research 75(6):1091 (2015) PMID 25736685

    Mutated KRAS (KRAS*) is a fundamental driver in the majority of pancreatic ductal adenocarcinomas (PDAC). Using an inducible mouse model of KRAS*-driven PDAC, we compared KRAS* genetic extinction with pharmacologic inhibition of MEK1 in tumor spheres and in vivo. KRAS* ablation blocked prolifera...
  12. Regulation of glutamine carrier proteins by RNF5 determines breast cancer response to ER stress-inducing chemotherapies.

    Cancer Cell 27(3):354 (2015) PMID 25759021 PMCID PMC4356903

    Many tumor cells are fueled by altered metabolism and increased glutamine (Gln) dependence. We identify regulation of the L-glutamine carrier proteins SLC1A5 and SLC38A2 (SLC1A5/38A2) by the ubiquitin ligase RNF5. Paclitaxel-induced ER stress to breast cancer (BCa) cells promotes RNF5 associatio...
  13. Regulation of Glutamine Carrier Proteins by RNF5 Determines Breast Cancer Response to ER Stress-Inducing Chemotherapies

    Cancer Cell 27(3):354 (2015)

    Many tumor cells are fueled by altered metabolism and increased glutamine (Gln) dependence. We identify regulation of the L-glutamine carrier proteins SLC1A5 and SLC38A2 (SLC1A5/38A2) by the ubiquitin ligase RNF5. Paclitaxel-induced ER stress to breast cancer (BCa) cells promotes RNF5 ...
  14. Regulation of Glutamine Carrier Proteins by RNF5 Determines Breast Cancer Response to ER Stress-Inducing Chemotherapies.

    Cancer Cell 27(3):354 (2015) PMID 25759021 PMCID PMC4356903

    Many tumor cells are fueled by altered metabolism and increased glutamine (Gln) dependence. We identify regulation of the L-glutamine carrier proteins SLC1A5 and SLC38A2 (SLC1A5/38A2) by the ubiquitin ligase RNF5. Paclitaxel-induced ER stress to breast cancer (BCa) cells promotes RNF5 associatio...
  15. SU2C phase Ib study of paclitaxel and MK-2206 in advanced solid tumors and metastatic breast cancer.

    JNCI Journal of the National Cancer Institute 107(3) (2015) PMID 25688104 PMCID PMC4342675

    There is preclinical synergism between taxanes and MK-2206. We aim to determine the maximum tolerated dose, safety, and activity of combining MK-2206 and paclitaxel in metastatic cancer. Patients received weekly doses of paclitaxel at 80mg/m2 on day 1, followed by MK-2206 orally on day 2 escalat...
  16. RET Fusion as a Novel Driver of Medullary Thyroid Carcinoma.

    Journal of Clinical Endocrinology & Metabolism 100(3):788 (2015) PMID 25546157 PMCID PMC4333032

    Oncogenic RET tyrosine kinase gene fusions and activating mutations have recently been identified in lung cancers, prompting initiation of targeted therapy trials in this disease. Although RET point mutation has been identified as a driver of tumorigenesis in medullary thyroid carcinoma (MTC), n...
  17. SU2C phase Ib study of paclitaxel and MK-2206 in advanced solid tumors and metastatic breast cancer.

    JNCI Journal of the National Cancer Institute 107(3) (2015) PMID 25688104

    There is preclinical synergism between taxanes and MK-2206. We aim to determine the maximum tolerated dose, safety, and activity of combining MK-2206 and paclitaxel in metastatic cancer. Patients received weekly doses of paclitaxel at 80mg/m2 on day 1, followed by MK-2206 orally on day 2 escalat...
  18. Clinical actionability enhanced through deep targeted sequencing of solid tumors.

    Clinical Chemistry 61(3):544 (2015) PMID 25626406 PMCID PMC4511273

    Further advances of targeted cancer therapy require comprehensive in-depth profiling of somatic mutations that are present in subpopulations of tumor cells in a clinical tumor sample. However, it is unclear to what extent such intratumor heterogeneity is present and whether it may affect clinica...
  19. Clinical Actionability Enhanced through Deep Targeted Sequencing of Solid Tumors.

    Clinical Chemistry 61(3):544 (2015) PMID 25626406

    Further advances of targeted cancer therapy require comprehensive in-depth profiling of somatic mutations that are present in subpopulations of tumor cells in a clinical tumor sample. However, it is unclear to what extent such intratumor heterogeneity is present and whether it may affect clinica...
  20. RET Fusion as a Novel Driver of Medullary Thyroid Carcinoma.

    Journal of Clinical Endocrinology & Metabolism 100(3):788 (2015) PMID 25546157 PMCID PMC4333032

    Oncogenic RET tyrosine kinase gene fusions and activating mutations have recently been identified in lung cancers, prompting initiation of targeted therapy trials in this disease. Although RET point mutation has been identified as a driver of tumorigenesis in medullary thyroid carcinoma (MTC), n...