CANCER DISCOVERY CONTENTS
ii | CANCER DISCOVERY MAY 2019 www.aacrjournals.org
MAY 2019 ≠ VOLUME 9 ≠ NUMBER 5
Engineering Multidimensional Evolutionary Forces to Combat Cancer . . . . . . . . . . . . . . . 587C .E . McCoach and T .G . Bivona
Patient-Driven Discovery, Therapeutic Targeting, and Post-Clinical Validation of a Novel AKT1 Fusion–Driven Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . 605E .K . Slotkin, D . Diolaiti, N .N . Shukla, F .S . Dela Cruz, J .J . Clark, G . Gundem, V .D . Yellapantula, M .F . Levine, D . You, P . Ma, S . Pachhal, G . Ibanez Sanchez, R . Benayed, A .A . Jungbluth, L .M . Smyth, A . Mauguen, I . Gushterova, H . Ding, L . Spraggon, R . Darnell, A . Califano, M . Ladanyi, E . Papaemmanuil, A .L . Kung, D .M . Hyman, and S .S . RobertsPrécis: The response to AKT inhibition in a pediatric patient with a LAMTOR1–AKT1 fusion confirms the AKT1 fusion as an oncogenic driver, and subsequent characterization of the fusion suggests potential ways to overcome resistance .
A Stromal Lysolipid–Autotaxin Signaling Axis Promotes Pancreatic Tumor Progression . . . 617F .R . Auciello, V . Bulusu, C . Oon, J . Tait-Mulder, M . Berry, S . Bhattacharyya, S . Tumanov, B .L . Allen-Petersen, J . Link, N .D . Kendsersky, E . Vringer, M . Schug, D . Novo, R .F . Hwang, R .M . Evans, C . Nixon, C . Dorrell, J .P . Morton, J .C . Norman, R .C . Sears, J .J . Kamphorst, and M .H . ShermanPrécis: Lysophosphatidylcholines secreted by activated stromal fibroblasts support pancreatic cancer cell proliferation and migration via autotaxin-mediated production of lysophosphatidic acid .
See commentary, p. 578
REVIEW
RESEARCH BRIEFS
Highlighted research articles . . . . . . . . . . . . . . . . . . . . . . . . 565
Important news stories affecting the community . . . . . . . . . 568
Targeting MCL1, Companies Aim to Unblock Apoptosis . . . . . 572
Selected highlights of recent articles of exceptional significance from the cancer literature . . . . . . . . . . . . . 573
For more News and Research Watch, visit Cancer Discovery online at http://cancerdiscovery .aacrjournals .org/CDNews .
In The Spotlight
A FATal Combination: Fibroblast-Derived Lipids and Cancer-Derived Autotaxin Promote Pancreatic Cancer Growth . . . . . . . . . . . . . . . . . . . 578G . Biffi and D .A . Tuveson
See article, p. 617
Metabolic Checkpoint of Immune Cells in Melanoma Brain Metastases . . . . . . . . . . . . 581C .A . Egelston and K . Margolin
See article, p. 628
Delivering a STINGing Blow to Small Cell Lung Cancer via Synergistic Inhibition of DNA-Damage Response and Immune-Checkpoint Pathways . . . . . . . . . . . . . . . . . . . . . 584J .B . Hiatt and D . MacPherson
See article, p. 646
IN THIS ISSUE
NEWS IN BRIEF
NEWS IN DEPTH
RESEARCH WATCH
ONLINE
VIEWS
Research. on April 30, 2021. © 2019 American Association for Cancercancerdiscovery.aacrjournals.org Downloaded from
MAY 2019 CANCER DISCOVERY | iii
Molecular Profi ling Reveals Unique Immune and Metabolic Features of Melanoma Brain Metastases . . . . . . . . . . . . . . . . . . . . 628G .M . Fischer, A . Jalali, D .A . Kircher, W .-C . Lee, J .L . McQuade, L .E . Haydu, A .Y . Joon, A . Reuben, M .P . de Macedo, F .C .L . Carapeto, C . Yang, A . Srivastava, C .R . Ambati, A . Sreekumar, C .W . Hudgens, B . Knighton, W . Deng, S .D . Ferguson, H .A . Tawbi, I .C . Glitza, J .E . Gershenwald, Y .N . Vashisht Gopal, P . Hwu, J .T . Huse, J .A . Wargo, P .A . Futreal, N . Putluri, A .J . Lazar, R .J . DeBerardinis, J .R . Marszalek, J . Zhang, S .L . Holmen, M .T . Tetzlaff, and M .A . DaviesPrécis: Comprehensive molecular profi ling of patient-matched melanoma brain metastases and extracranial metastases unveil signifi cant differences between these two metastatic populations .
See commentary, p. 581
Targeting DNA Damage Response Promotes Antitumor Immunity through STING-Mediated T-cell Activation in Small Cell Lung Cancer . . . . . . . . . . . . . . . 646T . Sen, B .L . Rodriguez, L . Chen, C .M . Della Corte, N . Morikawa, J . Fujimoto, S . Cristea, T . Nguyen, L . Diao, L . Li, Y . Fan, Y . Yang, J . Wang, B .S . Glisson, I .I . Wistuba, J . Sage, J .V . Heymach, D .L . Gibbons, and L .A . ByersPrécis: Pharmacologic inhibition of PARP and CHK1 increases expression of PD-L1 and
RESEARCHARTICLES
potentiates the antitumor effects of PD-L1 blockade via activation of the innate immune STING pathway .
See commentary, p. 584
BCL6 Evolved to Enable Stress Tolerance in Vertebrates and Is Broadly Required by Cancer Cells to Adapt to Stress . . . 662T .M . Fernando, R . Marullo, B . Pera Gresely, J .M . Phillip, S .N . Yang, G . Lundell-Smith, I . Torregroza, H . Ahn, T . Evans, B . Győrffy, G .G . Privé, M . Hirano, A .M . Melnick, and L . CerchiettiPrécis: An evolutionarily conserved HSF1–BCL6 axis mediates stress adaptation across vertebrates and promotes tolerance to chemotherapy in cancer cells, in part via repression of the transcription factor TOX .
AC icon indicates AuthorChoiceFor more information please visit http://www .aacrjournals .org
Sen and colleagues showed that treatment of human small cell lung cancer (SCLC) cell lines with inhibitors of the DNA damage response (DDR) components CHK1 and PARP resulted in increased expression of PD-L1 . Further, inhibition of either CHK1 or PARP in immunocompetent genetically engineered mouse models (GEMM) of SCLC resulted in increased levels of cytosolic DNA, which activates the cGAS–STING innate immune signaling pathway to induce IRF3 activation and subse-quently drive IFNβ-mediated increases in PD-L1 expression and T-cell recruitment in SCLC GEMMs . Consistent with these findings, treatment with a CHK1 or PARP inhibitor enhanced the efficacy of anti–PD-L1 therapy and resulted in SCLC tumor regression in vivo . Together, these findings suggest that combined targeting of DDR proteins and immune checkpoint blockade is a potential therapeutic strategy for patients with SCLC . For details, please see the article by Sen and colleagues on page 646 .
ON THE COVER
Research. on April 30, 2021. © 2019 American Association for Cancercancerdiscovery.aacrjournals.org Downloaded from
2019;9:OF6-679. Cancer Discov 9 (5)
Updated version
http://cancerdiscovery.aacrjournals.org/content/9/5
Access the most recent version of this article at:
E-mail alerts related to this article or journal.Sign up to receive free email-alerts
SubscriptionsReprints and
To order reprints of this article or to subscribe to the journal, contact the AACR Publications
Permissions
Rightslink site. Click on "Request Permissions" which will take you to the Copyright Clearance Center's (CCC)
.http://cancerdiscovery.aacrjournals.org/content/9/5To request permission to re-use all or part of this article, use this link
Research. on April 30, 2021. © 2019 American Association for Cancercancerdiscovery.aacrjournals.org Downloaded from