CANCER DISCOVERY CONTENTS

ii | CANCER DISCOVERY NOVEMBER 2018 www.aacrjournals.org

NOVEMBER 2018 ≠ VOLUME 8 ≠ NUMBER 11

C. Creasy, P. Greenberg, B.W. Carter, Z.A. Cooper, S.A. Rosenberg, M. Lotem, U. Sahin, G. Shakhar, E. Ruppin, J.A. Wargo, N. Friedman, A. Admon, and Y. SamuelsPrécis: Neoantigen prediction and HLA peptidomics identifies tumor-associated antigens and neoantigens in 16 melanomas from 7 patients and reveals a limited set of neoantigens responsible for antitumor immune responses.

Targeting the MTF2–MDM2 Axis Sensitizes Refractory Acute Myeloid Leukemia to Chemotherapy . . . . .1376H.B. Maganti, H. Jrade, C. Cafariello, J.L. Manias Rothberg, C.J. Porter, J. Yockell-Lelièvre, H.L. Battaion, S.T. Khan, J.P. Howard, Y. Li, A.T. Grzybowski, E. Sabri, A.J. Ruthenburg, F.J. Dilworth, T.J. Perkins, M. Sabloff, C.Y. Ito, and W.L. StanfordPrécis: MTF2 is downregulated by promoter hypermethylation in AML, resulting in loss of MDM2 transcriptional repression, reduced p53 expression, and resistance to standard induction chemotherapy. See commentary, p. 1348

The Genetic Landscape and Clonal Evolution of Breast Cancer Resist-ance to Palbociclib plus Fulvestrant in the PALOMA-3 Trial . . . . . . 1390B. O’Leary, R.J. Cutts, Y. Liu, S. Hrebien, X. Huang, K. Fenwick, F. André, S. Loibl, S. Loi, I. Garcia-Murillas, M. Cristofanilli, C. Huang Bartlett, and N.C. TurnerPrécis: Longitudinal analysis of samples from patients with estrogen receptor–positive breast cancer identified the mechanisms of resistance and clonal evolution to fulvestrant and palbociclib.See commentary, p. 1352

Prediction of DNA Repair Inhibitor Response in Short-Term Patient-Derived Ovarian Cancer Organoids . . . . . . . . . . . .1404S.J. Hill, B. Decker, E.A. Roberts, N.S. Horowitz, M.G. Muto, M.J. Worley Jr, C.M. Feltmate, M.R. Nucci, E.M. Swisher, H. Nguyen, C. Yang, R. Morizane, B.S. Kochupurakkal, K.T. Do, P.A. Konstantinopoulos, J.F. Liu, J.V. Bonventre, U.A. Matulonis, G.I. Shapiro, R.S. Berkowitz, C.P. Crum, and A.D. D’AndreaPrécis: Functional profiling of DNA repair in 33 patient-derived organoids from 22 patients with high-grade serous ovarian cancer combined with genomic analysis identified targetable DNA damage repair defects.

RESEARCH ARTICLES

Highlighted research articles . . . . . . . . . . . . . . . . . . . . . . . 1333

Important news stories affecting the community . . . . . . . . 1338

CAR T-cell Therapy for Solid Tumors? . . . . . . . . . . . . . . . . . . . . . 1341A Rethink for IO Biomarkers . . .1342

Selected highlights of recent articles of exceptional significance from the cancer literature . . . . . . . . . . . . 1343

For more News and Research Watch, visit Cancer Discovery online at http://cancerdiscovery.aacrjournals.org/CDNews.

In The Spotlight

Untangling the Role of Polycomb Complexes in Chemotherapy Resistance . . . . . . . . . . . . . . . . . . 1348C. Duy and A. MelnickSee article, p. 1376

Is ctDNA the Road Map to the Landscape of the Clonal Mutational Evolution in Drug Resistance? Lessons from the PALOMA-3 Study and Implications for Precision Medicine . . . . . . . . . . . 1352R. Schiff and R. JeselsohnSee article, p. 1390

Inhibition of HIF1 ̀Signaling: A Grand Slam for MDS Therapy? . . . . . . . . . .1355J. Chen and U. SteidlSee article, p. 1438

Mouse Models for Cancer Immunotherapy Research . . . 1358B. Olson, Y. Li, Y. Lin, E.T. Liu, and A. Patnaik

Combined Analysis of Antigen Presentation and T-cell Recognition Reveals Restricted Immune Responses in Melanoma . . . . . . 1366S. Kalaora, Y. Wolf, T. Feferman, E. Barnea, E. Greenstein, D. Reshef, I. Tirosh, A. Reuben, S. Patkar, R. Levy, J. Quinkhardt, T. Omokoko, N. Qutob, O. Golani, J. Zhang, X. Mao, X. Song, C. Bernatchez, C. Haymaker, M.-A. Forget,

IN THIS ISSUE

NEWS IN BRIEF

NEWS IN DEPTH

RESEARCH WATCH

ONLINE

VIEWS

MINI REVIEW

RESEARCH BRIEFS

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Crebbp Loss Drives Small Cell Lung Cancer and Increases Sensitivity to HDAC Inhibition . . . . . . . . . . . . . . . . . . . . .1422D. Jia, A. Augert, D.-W. Kim, E. Eastwood, N. Wu, A.H. Ibrahim, K.-B. Kim, C.T. Dunn, S.P.S. Pillai, A.F. Gazdar, H. Bolouri, K.-S. Park, and D. MacPhersonPrécis: Loss of the tumor suppressor CREBBP results in loss of histone acetylase–mediated activation of genes that suppress epithelial-to-mesenchymal transition in small cell lung cancer.

Pathobiological Pseudohypoxia as a Putative Mechanism Underlying Myelodysplastic Syndromes . . . . . . . . 1438Y. Hayashi, Y. Zhang, A. Yokota, X. Yan, J. Liu, K. Choi,B. Li, G. Sashida, Y. Peng, Z. Xu, R. Huang, L. Zhang,G.M. Freudiger, J. Wang, Y. Dong, Y. Zhou, J. Wang, L. Wu, J. Bu, A. Chen, X. Zhao, X. Sun, K. Chetal, A. Olsson, M. Watanabe, L.E. Romick-Rosendale, H. Harada, L.-Y. Shih, W. Tse, J.P. Bridges, M.A. Caligiuri, T. Huang,Y. Zheng, D.P. Witte, Q.-f. Wang, C.-K. Qu, N. Salomonis, H.L. Grimes, S.D. Nimer, Z. Xiao, and G. HuangPrécis: Hypoxia-independent activation of HIF1α is necessary and suffi cient for development of myelodysplastic syndromes, suggesting the HIF1α pathway as a potential therapeutic target.

See commentary, p. 1355

Cholinergic Signaling via Muscarinic Receptors Directly and Indirectly Suppresses Pancreatic Tumorigenesis and Cancer Stemness . . . . . . . . . . . . . . . 1458B.W. Renz, T. Tanaka, M. Sunagawa, R. Takahashi,Z. Jiang, M. Macchini, Z. Dantes, G. Valenti, R.A. White,

M.A. Middelhoff, M. Ilmer, P.E. Oberstein, M.K. Angele,H. Deng, Y. Hayakawa, C.B. Westphalen, J. Werner,H. Remotti, M. Reichert, Y.H. Tailor, K. Nagar, R.A. Friedman, A.C. Iuga, K.P. Olive, and T.C. WangPrécis: CHRM1-dependent parasympathetic nerve signaling inhibits pancreatic tumor growth by suppressing expansion of myeloid cells and cancer stem cells and by inhibiting EGFR/MAPK and PI3K/AKT pathway activation.

Multiple Routes to Oncogenesis Are Promoted by the Human Papillomavirus–Host Protein Network . . . . . . . . . . . . . . . 1474M. Eckhardt, W. Zhang, A.M. Gross, J. Von Dollen, J.R. Johnson, K.E. Franks-Skiba, D.L. Swaney, T.L. Johnson, G.M. Jang, P.S. Shah, T.M. Brand, J. Archambault, J.F. Kreisberg, J.R. Grandis, T. Ideker, and N.J. KroganPrécis: Integration of the HPV–human protein–protein interaction network with tumor mutation profi les uncovers oncogene HPV interactions that phenocopy recurrent mutations in HPV-negative cancers.

Corrections

Correction: A First-in-Human Phase IStudy of the ATP-Competitive AKT Inhibitor Ipatasertib Demonstrates Robust and Safe Targeting of AKT in Patients with Solid Tumors . . . . . . . . . . 1490

Correction: Phase I Dose-Escalation Study of Taselisib, an Oral PI3K Inhibitor, in Patients with Advanced Solid Tumors . . . . . . . . . . . . . . . . . . . . . . . . 1491

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Hill and colleagues profiled DNA-repair activity to discover potential therapeu-tic vulnerabilities in 33 organoid cultures derived from 22 patients with high-grade serous ovarian cancer (HGSC). The majority of HGSC organoids exhibited functional homologous recombination (HR) and were insensitive to agents tar-geting HR defects including the PARP inhibitor olaparib. Although genetic alter-ations predicted to affect HR occurred more frequently, only 2 of 34 organoid cultures were olaparib-sensitive, indicating a lack of functional HR. Replication fork instability occurred in 61% of tested cultures and was linked to sensitivity to carbo-platin, prexasertib, and VE-822. Combining prexasertib with carboplatin or gemcitabine could induce fork instability and replication stress in fork-stable lines. Together, these findings indicate that functional organoid profiling in concert with genomic analysis may aid the discovery of targetable DNA damage repair defects in patients with HGSC. For details, please see the article by Hill and colleagues on page 1404.

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