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Page 1
CDK4/6 Inhibition Augments Antitumor Immunity by Enhancing T-cell Activation.
Deng J, Wang ES, Jenkins RW, Li S, Dries R, Yates K, Chhabra S, Huang W, Liu H, Aref AR, Ivanova E, Paweletz CP, Bowden M, Zhou CW, Herter-Sprie GS, Sorrentino JA, Bisi JE, Lizotte PH, Merlino AA, Quinn MM, Bufe LE, Yang A, Zhang Y, Zhang H, Gao P, Chen T, Cavanaugh ME, Rode AJ, Haines E, Roberts PJ, Strum JC, Richards WG, Lorch JH, Parangi S, Gunda V, Boland GM, Bueno R, Palakurthi S, Freeman GJ, Ritz J, Haining WN, Sharpless NE, Arthanari H, Shapiro GI, Barbie DA, Gray NS, Wong KK. Deng J, et al. Cancer Discov. 2018 Feb;8(2):216-233. doi: 10.1158/2159-8290.CD-17-0915. Epub 2017 Nov 3. Cancer Discov. 2018. PMID: 29101163 Free PMC article.
To enhance the efficacy of existing immunotherapies, we screened for small molecules capable of increasing the activity of T cells suppressed by PD-1. Here, we show that short-term exposure to small-molecule inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6) significa …
To enhance the efficacy of existing immunotherapies, we screened for small molecules capable of increasing the activity of T cells suppresse …
Ex Vivo Profiling of PD-1 Blockade Using Organotypic Tumor Spheroids.
Jenkins RW, Aref AR, Lizotte PH, Ivanova E, Stinson S, Zhou CW, Bowden M, Deng J, Liu H, Miao D, He MX, Walker W, Zhang G, Tian T, Cheng C, Wei Z, Palakurthi S, Bittinger M, Vitzthum H, Kim JW, Merlino A, Quinn M, Venkataramani C, Kaplan JA, Portell A, Gokhale PC, Phillips B, Smart A, Rotem A, Jones RE, Keogh L, Anguiano M, Stapleton L, Jia Z, Barzily-Rokni M, Cañadas I, Thai TC, Hammond MR, Vlahos R, Wang ES, Zhang H, Li S, Hanna GJ, Huang W, Hoang MP, Piris A, Eliane JP, Stemmer-Rachamimov AO, Cameron L, Su MJ, Shah P, Izar B, Thakuria M, LeBoeuf NR, Rabinowits G, Gunda V, Parangi S, Cleary JM, Miller BC, Kitajima S, Thummalapalli R, Miao B, Barbie TU, Sivathanu V, Wong J, Richards WG, Bueno R, Yoon CH, Miret J, Herlyn M, Garraway LA, Van Allen EM, Freeman GJ, Kirschmeier PT, Lorch JH, Ott PA, Hodi FS, Flaherty KT, Kamm RD, Boland GM, Wong KK, Dornan D, Paweletz CP, Barbie DA. Jenkins RW, et al. Cancer Discov. 2018 Feb;8(2):196-215. doi: 10.1158/2159-8290.CD-17-0833. Epub 2017 Nov 3. Cancer Discov. 2018. PMID: 29101162 Free PMC article.
MDOTS/PDOTS isolated from mouse and human tumors retain autologous lymphoid and myeloid cell populations and respond to ICB in short-term three-dimensional microfluidic culture. Response and resistance to ICB was recapitulated using MDOTS derived from established immunocom …
MDOTS/PDOTS isolated from mouse and human tumors retain autologous lymphoid and myeloid cell populations and respond to ICB in short-term …
Gemcitabine and Chk1 Inhibitor AZD7762 Synergistically Suppress the Growth of Lkb1-Deficient Lung Adenocarcinoma.
Liu Y, Li Y, Wang X, Liu F, Gao P, Quinn MM, Li F, Merlino AA, Benes C, Liu Q, Gray NS, Wong KK. Liu Y, et al. Cancer Res. 2017 Sep 15;77(18):5068-5076. doi: 10.1158/0008-5472.CAN-17-0567. Epub 2017 Jul 28. Cancer Res. 2017. PMID: 28754670 Free PMC article.
In both Kras/p53/Lkb1 cell lines and a genetically engineered mouse model of Kras/p53/Lkb1-induced lung cancer, much higher rates of DNA damage occur, resulting in increased dependence on Chk1 checkpoint function. Here we demonstrate that short-term treatment with the Chk1 …
In both Kras/p53/Lkb1 cell lines and a genetically engineered mouse model of Kras/p53/Lkb1-induced lung cancer, much higher rates of DNA dam …
Transient CDK4/6 inhibition protects hematopoietic stem cells from chemotherapy-induced exhaustion.
He S, Roberts PJ, Sorrentino JA, Bisi JE, Storrie-White H, Tiessen RG, Makhuli KM, Wargin WA, Tadema H, van Hoogdalem EJ, Strum JC, Malik R, Sharpless NE. He S, et al. Sci Transl Med. 2017 Apr 26;9(387):eaal3986. doi: 10.1126/scitranslmed.aal3986. Sci Transl Med. 2017. PMID: 28446688 Free PMC article.
Conventional cytotoxic chemotherapy is highly effective in certain cancers but causes dose-limiting damage to normal proliferating cells, especially hematopoietic stem and progenitor cells (HSPCs). Serial exposure to cytotoxics causes a long-term hematopoietic compromise ( …
Conventional cytotoxic chemotherapy is highly effective in certain cancers but causes dose-limiting damage to normal proliferating cells, es …
Cellular Senescence Promotes Adverse Effects of Chemotherapy and Cancer Relapse.
Demaria M, O'Leary MN, Chang J, Shao L, Liu S, Alimirah F, Koenig K, Le C, Mitin N, Deal AM, Alston S, Academia EC, Kilmarx S, Valdovinos A, Wang B, de Bruin A, Kennedy BK, Melov S, Zhou D, Sharpless NE, Muss H, Campisi J. Demaria M, et al. Cancer Discov. 2017 Feb;7(2):165-176. doi: 10.1158/2159-8290.CD-16-0241. Epub 2016 Dec 15. Cancer Discov. 2017. PMID: 27979832 Free PMC article.
Using a transgenic mouse that permits tracking and eliminating senescent cells, we show that therapy-induced senescent (TIS) cells persist and contribute to local and systemic inflammation. Eliminating TIS cells reduced several short- and long-term effects of the drugs, in …
Using a transgenic mouse that permits tracking and eliminating senescent cells, we show that therapy-induced senescent (TIS) cells persist a …
Forging a signature of in vivo senescence.
Sharpless NE, Sherr CJ. Sharpless NE, et al. Nat Rev Cancer. 2015 Jul;15(7):397-408. doi: 10.1038/nrc3960. Nat Rev Cancer. 2015. PMID: 26105537 Review.
'Cellular senescence', a term originally defining the characteristics of cultured cells that exceed their replicative limit, has been broadened to describe durable states of proliferative arrest induced by disparate stress factors. ...We advocate that more-specific descrip …
'Cellular senescence', a term originally defining the characteristics of cultured cells that exceed their replicative limit, has been …
Long-term Benefit of PD-L1 Blockade in Lung Cancer Associated with JAK3 Activation.
Van Allen EM, Golay HG, Liu Y, Koyama S, Wong K, Taylor-Weiner A, Giannakis M, Harden M, Rojas-Rudilla V, Chevalier A, Thai T, Lydon C, Mach S, Avila AG, Wong JA, Rabin AR, Helmkamp J, Sholl L, Carter SL, Oxnard G, Janne P, Getz G, Lindeman N, Hammerman PS, Garraway LA, Hodi FS, Rodig SJ, Dranoff G, Wong KK, Barbie DA. Van Allen EM, et al. Cancer Immunol Res. 2015 Aug;3(8):855-63. doi: 10.1158/2326-6066.CIR-15-0024. Epub 2015 May 26. Cancer Immunol Res. 2015. PMID: 26014096 Free PMC article.
We performed comprehensive genomic profiling on a tumor and germline sample from a patient with refractory lung adenocarcinoma who achieved marked long-term clinical benefit from anti-PD-L1 therapy. We discovered activating somatic and germline amino acid variants in JAK3 …
We performed comprehensive genomic profiling on a tumor and germline sample from a patient with refractory lung adenocarcinoma who achieved …