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10 results on '"Boisvert, Jessica L."'

1. A landscape of response to drug combinations in non-small cell lung cancer

Author

Nair, Nishanth Ulhas, Greninger, Patricia, Zhang, Xiaohu, Friedman, Adam A., Amzallag, Arnaud, Cortez, Eliane, Sahu, Avinash Das, Lee, Joo Sang, Dastur, Anahita, Egan, Regina K., Murchie, Ellen, Ceribelli, Michele, Crowther, Giovanna S., Beck, Erin, McClanaghan, Joseph, Klump-Thomas, Carleen, Boisvert, Jessica L., Damon, Leah J., Wilson, Kelli M., Ho, Jeffrey, Tam, Angela, McKnight, Crystal, Michael, Sam, Itkin, Zina, Garnett, Mathew J., Engelman, Jeffrey A., Haber, Daniel A., Thomas, Craig J., Ruppin, Eytan, and Benes, Cyril H.

Published
2023
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2. Distinct but Concerted Roles of ATR, DNA-PK, and Chk1 in Countering Replication Stress during S Phase

Author

Buisson, Rémi, Boisvert, Jessica L, Benes, Cyril H, and Zou, Lee

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Biological Sciences, Cancer, 2.1 Biological and endogenous factors, Aetiology, Ataxia Telangiectasia Mutated Proteins, Cell Line, Tumor, Checkpoint Kinase 1, DNA Damage, DNA Replication, DNA, Single-Stranded, DNA-Activated Protein Kinase, Humans, Nuclear Proteins, Phosphorylation, Protein Kinases, Protein Processing, Post-Translational, Replication Origin, Ribonucleoside Diphosphate Reductase, S Phase, Stress, Physiological, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

The ATR-Chk1 pathway is critical for DNA damage responses and cell-cycle progression. Chk1 inhibition is more deleterious to cycling cells than ATR inhibition, raising questions about ATR and Chk1 functions in the absence of extrinsic replication stress. Here we show that a key role of ATR in S phase is to coordinate RRM2 accumulation and origin firing. ATR inhibitor (ATRi) induces massive ssDNA accumulation and replication catastrophe in a fraction of early S-phase cells. In other S-phase cells, however, ATRi induces moderate ssDNA and triggers a DNA-PK and Chk1-mediated backup pathway to suppress origin firing. The backup pathway creates a threshold such that ATRi selectively kills cells under high replication stress, whereas Chk1 inhibitor induces cell death at a lower threshold. The levels of ATRi-induced ssDNA correlate with ATRi sensitivity in a panel of cell lines, suggesting that ATRi-induced ssDNA could be predictive of ATRi sensitivity in cancer cells.

Published
2015

3. Supplementary Figures from mTOR Inhibition Specifically Sensitizes Colorectal Cancers with KRAS or BRAF Mutations to BCL-2/BCL-XL Inhibition by Suppressing MCL-1

Author

Faber, Anthony C., primary, Coffee, Erin M., primary, Costa, Carlotta, primary, Dastur, Anahita, primary, Ebi, Hiromichi, primary, Hata, Aaron N., primary, Yeo, Alan T., primary, Edelman, Elena J., primary, Song, Youngchul, primary, Tam, Ah Ting, primary, Boisvert, Jessica L., primary, Milano, Randy J., primary, Roper, Jatin, primary, Kodack, David P., primary, Jain, Rakesh K., primary, Corcoran, Ryan B., primary, Rivera, Miguel N., primary, Ramaswamy, Sridhar, primary, Hung, Kenneth E., primary, Benes, Cyril H., primary, and Engelman, Jeffrey A., primary

Published
2023
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4. Supplementary Material from mTOR Inhibition Specifically Sensitizes Colorectal Cancers with KRAS or BRAF Mutations to BCL-2/BCL-XL Inhibition by Suppressing MCL-1

Author

Faber, Anthony C., primary, Coffee, Erin M., primary, Costa, Carlotta, primary, Dastur, Anahita, primary, Ebi, Hiromichi, primary, Hata, Aaron N., primary, Yeo, Alan T., primary, Edelman, Elena J., primary, Song, Youngchul, primary, Tam, Ah Ting, primary, Boisvert, Jessica L., primary, Milano, Randy J., primary, Roper, Jatin, primary, Kodack, David P., primary, Jain, Rakesh K., primary, Corcoran, Ryan B., primary, Rivera, Miguel N., primary, Ramaswamy, Sridhar, primary, Hung, Kenneth E., primary, Benes, Cyril H., primary, and Engelman, Jeffrey A., primary

Published
2023
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5. Data from mTOR Inhibition Specifically Sensitizes Colorectal Cancers with KRAS or BRAF Mutations to BCL-2/BCL-XL Inhibition by Suppressing MCL-1

Author

Faber, Anthony C., primary, Coffee, Erin M., primary, Costa, Carlotta, primary, Dastur, Anahita, primary, Ebi, Hiromichi, primary, Hata, Aaron N., primary, Yeo, Alan T., primary, Edelman, Elena J., primary, Song, Youngchul, primary, Tam, Ah Ting, primary, Boisvert, Jessica L., primary, Milano, Randy J., primary, Roper, Jatin, primary, Kodack, David P., primary, Jain, Rakesh K., primary, Corcoran, Ryan B., primary, Rivera, Miguel N., primary, Ramaswamy, Sridhar, primary, Hung, Kenneth E., primary, Benes, Cyril H., primary, and Engelman, Jeffrey A., primary

Published
2023
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6. Assessment of ABT-263 activity across a cancer cell line collection leads to a potent combination therapy for small-cell lung cancer

Author

Faber, Anthony C., Farago, Anna F., Costa, Carlotta, Dastur, Anahita, Gomez-Caraballo, Maria, Robbins, Rebecca, Wagner, Bethany L., Rideout, William M., Jakubik, Charles T., Ham, Jungoh, Edelman, Elena J., Ebi, Hiromichi, Yeo, Alan T., Hata, Aaron N., Song, Youngchul, Patel, Neha U., March, Ryan J., Tam, Ah Ting, Milano, Randy J., Boisvert, Jessica L., Hicks, Mark A., Elmiligy, Sarah, Malstrom, Scott E., Rivera, Miguel N., Harada, Hisashi, Windle, Brad E., Ramaswamy, Sridhar, Benes, Cyril H., Jacks, Tyler, and Engelman, Jeffrey A.

Published
2015

7. Systematic identification of genomic markers of drug sensitivity in cancer cells

Author

Garnett, Mathew J., Edelman, Elena J., Heidorn, Sonja J., Greenman, Chris D., Dastur, Anahita, Lau, King Wai, Greninger, Patricia, Thompson, Richard I., Luo, Xi, Soares, Jorge, Liu, Qingsong, Iorio, Francesco, Surdez, Didier, Chen, Li, Milano, Randy J., Bignell, Graham R., Tam, Ah T., Davies, Helen, Stevenson, Jesse A., Barthorpe, Syd, Lutz, Stephen R., Kogera, Fiona, Lawrence, Karl, McLaren-Douglas, Anne, Mitropoulos, Xeni, Mironenko, Tatiana, Thi, Helen, Richardson, Laura, Zhou, Wenjun, Jewitt, Frances, Zhang, Tinghu, O’Brien, Patrick, Boisvert, Jessica L., Price, Stacey, Hur, Wooyoung, Yang, Wanjuan, Deng, Xianming, Butler, Adam, Choi, Hwan Geun, Chang, Jae Won, Baselga, Jose, Stamenkovic, Ivan, Engelman, Jeffrey A., Sharma, Sreenath V., Delattre, Olivier, Saez-Rodriguez, Julio, Gray, Nathanael S., Settleman, Jeffrey, Futreal, Andrew P., Haber, Daniel A., Stratton, Michael R., Ramaswamy, Sridhar, McDermott, Ultan, and Benes, Cyril H.

Published
2012
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8. Assessment of ABT-263 activity across a cancer cell line collection leads to a potent combination therapy for small-cell lung cancer

Author

Koch Institute for Integrative Cancer Research at MIT, Farago, Anna, Robbins, Rebecca, Wagner, Bethany L., Rideout, William M., Elmiligy, Sarah, Malstrom, Scott E., Jacks, Tyler E., Faber, Anthony C., Costa, Carlotta, Dastur, Anahita, Gomez-Caraballo, Maria, Jakubik, Charles T., Ham, Jungoh, Edelman, Elena J., Ebi, Hiromichi, Yeo, Alan T., Hata, Aaron N., Song, Youngchul, Patel, Neha U., March, Ryan J., Tam, Ah Ting, Milano, Randy J., Boisvert, Jessica L., Hicks, Mark A., Rivera, Miguel N., Harada, Hisashi, Windle, Brad E., Ramaswamy, Sridhar, Benes, Cyril H., Engelman, Jeffrey A., Jacks, Tyler E, Koch Institute for Integrative Cancer Research at MIT, Farago, Anna, Robbins, Rebecca, Wagner, Bethany L., Rideout, William M., Elmiligy, Sarah, Malstrom, Scott E., Jacks, Tyler E., Faber, Anthony C., Costa, Carlotta, Dastur, Anahita, Gomez-Caraballo, Maria, Jakubik, Charles T., Ham, Jungoh, Edelman, Elena J., Ebi, Hiromichi, Yeo, Alan T., Hata, Aaron N., Song, Youngchul, Patel, Neha U., March, Ryan J., Tam, Ah Ting, Milano, Randy J., Boisvert, Jessica L., Hicks, Mark A., Rivera, Miguel N., Harada, Hisashi, Windle, Brad E., Ramaswamy, Sridhar, Benes, Cyril H., Engelman, Jeffrey A., and Jacks, Tyler E

Abstract

BH3 mimetics such as ABT-263 induce apoptosis in a subset of cancer models. However, these drugs have shown limited clinical efficacy as single agents in small-cell lung cancer (SCLC) and other solid tumor malignancies, and rational combination strategies remain underexplored. To develop a novel therapeutic approach, we examined the efficacy of ABT-263 across >500 cancer cell lines, including 311 for which we had matched expression data for select genes. We found that high expression of the proapoptotic gene Bcl2-interacting mediator of cell death (BIM) predicts sensitivity to ABT-263. In particular, SCLC cell lines possessed greater BIM transcript levels than most other solid tumors and are among the most sensitive to ABT-263. However, a subset of relatively resistant SCLC cell lines has concomitant high expression of the antiapoptotic myeloid cell leukemia 1 (MCL-1). Whereas ABT-263 released BIM from complexes with BCL-2 and BCL-XL, high expression of MCL-1 sequestered BIM released from BCL-2 and BCL-XL, thereby abrogating apoptosis. We found that SCLCs were sensitized to ABT-263 via TORC1/2 inhibition, which led to reduced MCL-1 protein levels, thereby facilitating BIM-mediated apoptosis. AZD8055 and ABT-263 together induced marked apoptosis in vitro, as well as tumor regressions in multiple SCLC xenograft models. In a Tp53; Rb1 deletion genetically engineered mouse model of SCLC, the combination of ABT-263 and AZD8055 significantly repressed tumor growth and induced tumor regressions compared with either drug alone. Furthermore, in a SCLC patient-derived xenograft model that was resistant to ABT-263 alone, the addition of AZD8055 induced potent tumor regression. Therefore, addition of a TORC1/2 inhibitor offers a therapeutic strategy to markedly improve ABT-263 activity in SCLC., United States. Dept. of Defense (Grant W81-XWH-13-1-0323), National Cancer Institute (U.S.) (Cancer Center Support Grant P30-CA14051)

Published
2015

9. mTOR Inhibition Specifically Sensitizes Colorectal Cancers with KRAS or BRAF Mutations to BCL-2/BCL-XL Inhibition by Suppressing MCL-1

Author

Faber, Anthony C., primary, Coffee, Erin M., additional, Costa, Carlotta, additional, Dastur, Anahita, additional, Ebi, Hiromichi, additional, Hata, Aaron N., additional, Yeo, Alan T., additional, Edelman, Elena J., additional, Song, Youngchul, additional, Tam, Ah Ting, additional, Boisvert, Jessica L., additional, Milano, Randy J., additional, Roper, Jatin, additional, Kodack, David P., additional, Jain, Rakesh K., additional, Corcoran, Ryan B., additional, Rivera, Miguel N., additional, Ramaswamy, Sridhar, additional, Hung, Kenneth E., additional, Benes, Cyril H., additional, and Engelman, Jeffrey A., additional

Published
2014
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10. Abstract C263: mTOR inhibition specifically sensitizes colorectal cancers with KRAS or BRAF mutations to BCL-2/BCL-XL inhibition by suppressing MCL-1.

Author

Coffee, Erin M., primary, Faber, Anthony C., additional, Costa, Carlotta, additional, Dastur, Anahita, additional, Ebi, Hiromichi, additional, Hata, Aaron N., additional, Yeo, Alan T., additional, J, Elena, additional, Song, Youngchul, additional, Tam, Ah Ting, additional, Boisvert, Jessica L., additional, Milano, Randy J., additional, Roper, Jatin, additional, Kodack, David P., additional, Jain, Rakesh K., additional, Corcoran, Ryan B., additional, Rivera, Miguel N., additional, Ramaswamy, Sridhar, additional, Hung, Kenneth E., additional, Benes, Cyril H., additional, and Engelman, Jeffrey A., additional

Published
2013
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