bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Genetic Subtyping and Phenotypic Characterization of the Immune Microenvironment and MYC/BCL2 Double Expression Reveal Heterogeneity in Diffuse Large B-cell Lymphoma
Authors: Xu-Monette Zijun Y. , Wei Li , Fang Xiaosheng , Au Qingyan , Nunns Harry , Nagy Máté , Tzankov Alexandar , Zhu Feng , Visco Carlo , Bhagat Govind , Dybkaer Karen , Chiu April , Tam Wayne , Zu Youli , Hsi Eric D. , Hagemeister Fredrick B. , Sun Xiaoping , Han Xin , Go Heounjeong , Ponzoni Maurilio , Ferreri Andrés J.M. , Møller Michael B. , Parsons Benjamin M. , van Krieken J. Han , Piris Miguel A. , Winter Jane N. , Li Yong , Xu Bing , Albitar Maher , You Hua , Young Ken H.
Published: April 2023

AbstractPurpose:
Diffuse large B-cell lymphoma (DLBCL) is molecularly and clinically heterogeneous, and can be subtyped according to genetic alterations, cell-of-origin, or microenvironmental signatures using high-throughput genomic data at the DNA or RNA level. Although high-throughput proteomic profiling has not been available for DLBCL subtyping, MYC/BCL2 protein double expression (DE) is an established prognostic biomarker in DLBCL. The purpose of this study is to reveal the relative prognostic roles of DLBCL genetic, phenotypic, and microenvironmental biomarkers.
Experimental Design:
We performed targeted next-generation sequencing; IHC for MYC, BCL2, and FN1; and fluorescent multiplex IHC for microenvironmental markers in a large cohort of DLBCL. We performed correlative and prognostic analyses within and across DLBCL genetic subtypes and MYC/BCL2 double expressors.
Results:
We found that MYC/BCL2 double-high-expression (DhE) had significant adverse prognostic impact within the EZB genetic subtype and LymphGen-unclassified DLBCL cases but not within MCD and ST2 genetic subtypes. Conversely, KMT2D mutations significantly stratified DhE but not non-DhE DLBCL. T-cell infiltration showed favorable prognostic effects within BN2, MCD, and DhE but unfavorable effects within ST2 and LymphGen-unclassified cases. FN1 and PD-1–high expression had significant adverse prognostic effects within multiple DLBCL genetic/phenotypic subgroups. The prognostic effects of DhE and immune biomarkers within DLBCL genetic subtypes were independent although DhE and high Ki-67 were significantly associated with lower T-cell infiltration in LymphGen-unclassified cases.
Conclusions:
Together, these results demonstrated independent and additive prognostic effects of phenotypic MYC/BCL2 and microenvironment biomarkers and genetic subtyping in DLBCL prognostication, important for improving DLBCL classification and identifying prognostic determinants and therapeutic targets.
Data from A Prospective Observational Study of Active Surveillance in Primary Desmoid Fibromatosis
Authors: Colombo Chiara , Fiore Marco , Grignani Giovanni , Tolomeo Francesco , Merlini Alessandra , Palassini Elena , Collini Paola , Stacchiotti Silvia , Casali Paolo Giovanni , Perrone Federica , Mariani Luigi , Gronchi Alessandro
Published: April 2023

AbstractPurpose:
To prospectively assess the behavior of primary sporadic (not familial adenomatous polyposis–associated) desmoid fibromatosis (DF) managed by active surveillance (AS).
ExperimentalDesign:
This is an Italian prospective, multicenter, observational study (NCT 02547831) including patients ≥16 years with primary sporadic DF at any site. Patients were assessed by Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1. Primary endpoint was progression-free survival (PFS) at 3 years. Treatment-free survival (TFS) was also analyzed. PFS and TFS were calculated by Kaplan–Meier plots and compared by log-rank test. Cox proportional hazard multivariable regression analyses were performed.
Results:
From 2013 to 2018, 108 consecutive patients were included (82% female); median age was 39 years; median size was 51 mm. CTNNB1 mutations were T41A (50%), S45F (12%), other (19%), wild-type (19%). At 32.3-month median follow-up, 42 of 108 (39%) showed RECIST progression. Spontaneous regression was initially observed in 27 of 108 (25%), while it followed dimensional progression in another 33 of 108 (31%). PFS at 36 months was 54.5% [95% confidence interval (CI), 44.9%–66.1%]. Thirty-five of 108 (32%) patients received active treatment, 18 of 108 (17%) after RECIST progression and 17 of 108 (15%) after symptomatic progression. TFS at 36 months was 65.9% (95% CI, 57.3%–75.9%). Larger tumor size and extremity location were associated to shorter TFS and a trend for S45F mutation was also observed (P = 0.06), while none of the mentioned variables was significantly associated with PFS.
Conclusions:
In primary DF, AS can be proposed, because disease stabilization and spontaneous regression frequently occur. However, extra care should be taken for patients with tumors of larger size, extremity location, and S45F mutation.

See related commentary by Greene and Van Tine, p. 3911
Data from MAPK Pathway Genetic Alterations Are Associated with Prolonged Overall Survival in Low-Grade Serous Ovarian Carcinoma
Authors: Manning-Geist Beryl , Gordhandas Sushmita , Liu Ying L. , Zhou Qin , Iasonos Alexia , Da Cruz Paula Arnaud , Mandelker Diana , Roche Kara Long , Zivanovic Oliver , Maio Anna , Kemel Yelena , Chi Dennis S. , O'Cearbhaill Roisin E. , Aghajanian Carol , Weigelt Britta , Chui M. Herman , Grisham Rachel N.
Published: April 2023

AbstractPurpose:
To characterize the somatic mutational landscape, investigate associations between genetic alterations and clinical outcomes, and determine the prevalence of pathogenic germline mutations in low-grade serous ovarian carcinomas (LGSC).
Experimental Design:
Patients with LGSC tumors who underwent panel-based sequencing of up to 505 genes were identified. Data on somatic and germline mutations; copy-number alterations; and clinicopathologic features, including age at diagnosis, platinum sensitivity, and overall survival (OS), were collected.
Results:
Following central pathology rereview, 119 patients with LGSC were identified for analysis. Of these, 110 (92%) had advanced-stage disease (stages III/IV). Somatic KRAS (33%), NRAS (11%), EIF1AX (10%), and BRAF (11%) alterations were the most common; MAPK pathway alterations were found in 60% (n = 71) of LGSCs. KRAS mutations were significantly associated with age at diagnosis more than 50 years (P = 0.02) and platinum-sensitive disease (P = 0.03). On multivariate analysis, MAPK pathway alterations (P = 0.02) and platinum sensitivity (P = 0.005) were significantly associated with improved OS. Seventy-nine patients (66%) underwent germline genetic testing; seven pathogenic germline mutations were identified: MUTYH (n = 2), BAP1 (n = 1), RB1 (n = 1), CHEK2 (n = 1), APC (n = 1), and FANCA (n = 1). There were no germline BRCA1/2 mutations. One germline MUTYH-associated LGSC harbored loss-of-heterozygosity at the MUTYH locus, and the patient with the germline BAP1 mutation also harbored a somatic BAP1 frameshift mutation.
Conclusions:
This study showed that MAPK pathway alterations in LGSC, including KRAS mutations, are independently associated with platinum sensitivity and prolonged survival. Germline data, which were limited, identified few pathogenic germline mutations in patients with LGSC.

See related commentary by Veneziani and Oza, p. 4357
Data from SHR-1701, a Bifunctional Fusion Protein Targeting PD-L1 and TGFβ, for Recurrent or Metastatic Cervical Cancer: A Clinical Expansion Cohort of a Phase I Study
Authors: Feng Jifeng , Tang Dihong , Wang Jing , Zhou Qi , Peng Jin , Lou Hanmei , Sun Yuping , Cai Yunlang , Chen Hongmin , Yang Junqin , Liu Pan , Wang Linna , Zou Jianjun
Published: April 2023

AbstractPurpose:
Patients with recurrent or metastatic cervical cancer have limited treatment options after platinum-containing treatment. We initiated a phase I study to assess SHR-1701, a novel bifunctional fusion protein composed of a mAb against programmed death ligand 1 (PD-L1) fused with the extracellular domain of TGFβ receptor II, in solid tumors (NCT03774979). Here, results from the cervical cancer cohort are presented.
Patients and Methods:
Patients with recurrent or metastatic cervical cancer who progressed during or after platinum-based therapy were enrolled to receive SHR-1701 at 30 mg/kg every 3 weeks. Primary endpoint was objective response rate (ORR) per RECIST v1.1.
Results:
In total, 32 patients were recruited. ORR was 15.6% [95% confidence interval (CI), 5.3–32.8], and disease control rate was 50.0% (95% CI, 31.9–68.1). Responses were still ongoing in 80.0% of the responders; 6-month duration of response rate was 80.0% (95% CI, 20.4–96.9). Median progression-free survival (PFS) was 2.7 months (95% CI, 1.4–4.1). Of note, as assessed by immune-modified RECIST, median PFS was 4.1 months (95% CI, 1.6–4.3). Overall survival rate at 12 months was 54.6% (95% CI, 31.8–72.7). Treatment-related adverse events of grade 3 or 4 were reported in 11 (34.4%) patients. No treatment-related deaths occurred. No difference in ORR was found between patients with PD-L1 combined positive score ≥1 or <1; patients with high phosphorylated SMAD2 level in immune cells or tumor cells had numerically higher ORR.
Conclusions:
SHR-1701 exhibits encouraging antitumor activity and controllable safety in patients with recurrent or metastatic cervical cancer after platinum-based regimens, and therefore might provide another treatment option for this population.

See related commentary by Miller and Friedman, p. 5238
Data from A Phase 1 First-in-Human Study of FS118, a Tetravalent Bispecific Antibody Targeting LAG-3 and PD-L1 in Patients with Advanced Cancer and PD-L1 Resistance
Authors: Yap Timothy A. , LoRusso Patricia M. , Wong Deborah J. , Hu-Lieskovan Siwen , Papadopoulos Kyriakos P. , Holz Josefin-Beate , Grabowska Urszula , Gradinaru Cristian , Leung Kin-Mei , Marshall Sylwia , Reader Claire S. , Russell Roslin , Sainson Richard C.A. , Seal Claire J. , Shepherd Christopher J. , Germaschewski Fiona , Gliddon Daniel , Stern Omer , Young Lesley , Brewis Neil , Kayitalire Louis , Morrow Michelle
Published: April 2023

AbstractPurpose:
This phase 1 study (NCT03440437) evaluated the safety, tolerability, pharmacokinetics (PK), and activity of FS118, a bispecific antibody–targeting LAG-3 and PD-L1, in patients with advanced cancer resistant to anti–PD-(L)1 therapy.
Patients and Methods:
Patients with solid tumors, refractory to anti–PD-(L)1–based therapy, received intravenous FS118 weekly with an accelerated dose titration design (800 μg to 0.3 mg/kg) followed by 3+3 ascending dose expansion (1 to 20 mg/kg). Primary objectives were safety, tolerability, and PK. Additional endpoints included antitumor activity, immunogenicity, and pharmacodynamics.
Results:
Forty-three patients with a median of three prior regimens in the locally advanced/metastatic setting, including at least one anti–PD-(L)1 regimen, received FS118 monotherapy. FS118 was well tolerated, with no serious adverse events relating to FS118 reported. No dose-limiting toxicities (DLT) were observed, and an MTD was not reached. The recommended phase 2 dose of FS118 was established as 10 mg/kg weekly. The terminal half-life was 3.9 days. Immunogenicity was transient. Pharmacodynamic activity was prolonged throughout dosing as demonstrated by sustained elevation of soluble LAG-3 and increased peripheral effector cells. The overall disease control rate (DCR) was 46.5%; this disease control was observed as stable disease, except for one late partial response. Disease control of 54.8% was observed in patients receiving 1 mg/kg or greater who had acquired resistance to PD-(L)1–targeted therapy.
Conclusions:
FS118 was well tolerated with no DLTs observed up to and including 20 mg/kg QW. Further studies are warranted to determine clinical benefit in patients who have become refractory to anti–PD-(L)1 therapy.

See related commentary by Karapetyan and Luke, p. 835
Data from ACTA2 Expression Predicts Survival and Is Associated with Response to Immune Checkpoint Inhibitors in Gastric Cancer
Authors: Park Sunho , Karalis John D. , Hong Changjin , Clemenceau Jean R. , Porembka Matthew R. , Kim In-Ho , Lee Sung Hak , Wang Sam C. , Cheong Jae-Ho , Hwang Tae Hyun
Published: April 2023

AbstractPurpose:
We sought to identify biomarkers that predict overall survival (OS) and response to immune checkpoint inhibitors (ICI) for patients with gastric cancer.
Experimental Design:
This was a retrospective study of multiple independent cohorts of patients with gastric cancer. The association between tumor ACTA2 expression and OS and ICI response were determined in patients whose tumors were analyzed with bulk mRNA sequencing. Single-cell RNA sequencing (scRNA-seq) and digital spatial profiling data were used to compare tumors from patients with gastric cancer who did and did not respond to ICI.
Results:
Increasing tumor ACTA2 expression was independently associated with worse OS in a 567-patient discovery cohort [HR, 1.28 per unit increase; 95% confidence interval (CI), 1.02–1.62]. This finding was validated in three independent cohorts (n = 974; HR, 1.52 per unit increase; 95% CI, 1.34–1.73). Of the 108 patients treated with ICI, 56% of patients with low ACTA2 expression responded to ICI versus 25% of patients with high ACTA2 expression (P = 0.004). In an analysis of a publicly available scRNA-seq dataset of 5 microsatellite instability-high patients treated with ICI, the patient who responded to ICI had lower tumor stromal ACTA2 expression than the 4 nonresponders. Digital spatial profiling of tumor samples from 4 ICI responders and 5 ICI nonresponders revealed that responders may have lower ACTA2 expression in α-SMA–positive cancer-associated fibroblasts (CAF) than nonresponders (median: 5.00 vs. 5.50).
Conclusions:
ACTA2 expression is associated with survival and ICI response in patients with gastric cancer. ACTA2 expression in CAFs, but not in other cellular compartments, appears to be associated with ICI response.
Data from Overcoming Barriers to Tumor Genomic Profiling through Direct-to-Patient Outreach
Authors: Doe-Tetteh Seyram A. , Camp Sabrina Y. , Reales Dalicia , Crowdis Jett , Noronha Anne Marie , Wolff Bernadette , Alano Tina , Galle Jesse , Selcuklu S. Duygu , Viale Agnes , Socci Nicholas D. , Liu Ying L. , Tew William P. , Aghajanian Carol , Ladanyi Marc , He Meng Xiao , AlDubayan Saud H. , Mazor Roei David , Shpilberg Ofer , Hershkovitz-Rokah Oshrat , Riancho Jose A. , Hernandez Jose L. , Gonzalez-Vela M. Carmen , Buthorn Justin J. , Wilson Manda , Webber Amy E. , Yabe Mariko , Petrova-Drus Kseniya , Rosenblum Marc , Durham Benjamin H. , Abdel-Wahab Omar , Berger Michael F. , Donoghue Mark T.A. , Kung Andrew L. , Glade Bender Julia , Shukla Neerav N. , Funt Samuel A. , Dogan Ahmet , Soslow Robert A. , Al-Ahmadie Hikmat , Feldman Darren R. , Van Allen Eliezer M. , Diamond Eli L. , Solit David B.
Published: April 2023

AbstractPurpose:
To overcome barriers to genomic testing for patients with rare cancers, we initiated a program to offer free clinical tumor genomic testing worldwide to patients with select rare cancer subtypes.
Experimental Design:
Patients were recruited through social media outreach and engagement with disease-specific advocacy groups, with a focus on patients with histiocytosis, germ cell tumors (GCT), and pediatric cancers. Tumors were analyzed using the MSK-IMPACT next-generation sequencing assay with the return of results to patients and their local physicians. Whole-exome recapture was performed for female patients with GCTs to define the genomic landscape of this rare cancer subtype.
Results:
A total of 333 patients were enrolled, and tumor tissue was received for 288 (86.4%), with 250 (86.8%) having tumor DNA of sufficient quality for MSK-IMPACT testing. Eighteen patients with histiocytosis have received genomically guided therapy to date, of whom 17 (94%) have had clinical benefit with a mean treatment duration of 21.7 months (range, 6–40+). Whole-exome sequencing of ovarian GCTs identified a subset with haploid genotypes, a phenotype rarely observed in other cancer types. Actionable genomic alterations were rare in ovarian GCT (28%); however, 2 patients with ovarian GCTs with squamous transformation had high tumor mutational burden, one of whom had a complete response to pembrolizumab.
Conclusions:
Direct-to-patient outreach can facilitate the assembly of cohorts of rare cancers of sufficient size to define their genomic landscape. By profiling tumors in a clinical laboratory, results could be reported to patients and their local physicians to guide treatment.
Data from Molecular Clusters and Tumor-Immune Drivers of IgM Monoclonal Gammopathies
Authors: Mondello Patrizia , Paludo Jonas , Novak Joseph P. , Wenzl Kerstin , Yang Zhi-Zhang , Jalali Shahrzad , Krull Jordan E. , Braggio Esteban , Dasari Surendra , Manske Michelle K. , Abeykoon Jithma A. , Sarangi Vivekananda , Kapoor Prashant , Paulus Aneel , Reeder Craig B. , Ailawadhi Sikander , Chanan-Khan Asher A. , Kyle Robert A. , Gertz Morie A. , Novak Anne J. , Ansell Stephen M.
Published: April 2023

AbstractPurpose:
IgM monoclonal gammopathy of undetermined significance (MGUS) and Waldenström macroglobulinemia (WM) represent a disease spectrum with highly varied therapeutic management, ranging from observation to chemoimmunotherapy. The current classification relies solely on clinical features and does not explain the heterogeneity that exists within each of these conditions. Further investigation is warranted to shed light on the biology that may account for the clinical differences.
Experimental Design:
We used bone marrow (BM) clonal CD19+ and/or CD138+ sorted cells, matched BM supernatant, and peripheral blood serum from 32 patients (7 MGUS, 25 WM) to perform the first multi-omics approach including whole-exome sequencing, RNA sequencing, proteomics, metabolomics, and mass cytometry.
Results:
We identified three clusters with distinct pathway activation, immune content, metabolomic, and clinical features. Cluster 1 included only patients with WM and was characterized by transcriptional silencing of genes involved in cell cycle and immune response, enrichment of mitochondrial metabolism, infiltration of senescent T effector memory cells, and aggressive clinical behavior. Genetic/structural alterations of TNFAIP3 were distinct events of this cluster. Cluster 2 comprised both MGUS and WM patients with upregulation of inflammatory response, senescence and glycolysis signatures, increased activated T follicular helper and T regulatory cells, and indolent clinical behavior. Cluster 3 also included both MGUS and WM patients and exhibited intermediate features, including proliferative and inflammatory signaling, as well as glycolysis and mitochondrial metabolism.
Conclusions:
We have identified three distinct molecular clusters, suggesting a potential biologic classification that may have therapeutic implications.
Data from Characterization of Cell-Free DNA Size Distribution in Osteosarcoma Patients
Authors: Udomruk Sasimol , Phanphaisarn Areerak , Kanthawang Thanat , Sangphukieo Apiwat , Sutthitthasakul Songphon , Tongjai Siripong , Teeyakasem Pimpisa , Thongkumkoon Patcharawadee , Orrapin Santhasiri , Moonmuang Sutpirat , Klangjorhor Jeerawan , Pasena Arnat , Suksakit Pathacha , Dissook Sivamoke , Puranachot Pitithat , Settakorn Jongkolnee , Pusadee Tonapha , Pruksakorn Dumnoensun , Chaiyawat Parunya
Published: April 2023

AbstractPurpose:
Cell-free DNA (cfDNA) analysis is a powerful tool for noninvasively predicting patient outcomes. We analyzed the size distribution of cfDNA and assessed its prognostic and diagnostic values in an osteosarcoma cohort.
Experimental Design:
The fragment size distribution and level of cfDNA were analyzed in 15 healthy donors and 50 patients with osteosarcoma using automated capillary electrophoresis. The prognostic performance of cfDNA size analysis was assessed using univariate and multivariable analyses. By performing whole-genome sequencing of matched cfDNA and osteosarcoma tissue samples, we investigated the correlation between the size and mutation profiles of cfDNA and the mutation concordance between cfDNA and paired tissue tumors.
Results:
The size of cfDNA fragments in patients with osteosarcoma was significantly shorter than in healthy donors, with the integrative analysis of size distribution and level of cfDNA achieving a high specificity and sensitivity of 100%. The short cfDNA fragment (150-bp cut-off) was an independent prognostic predictor in this osteosarcoma cohort [HR, 9.03; 95% confidence interval (CI), 1.13–72.20; P = 0.038]. Shortened cfDNA fragments were found to be a major source of mutations. Enrichment of cfDNA fragments with less than or equal to 150 bp by in silico size selection remarkedly improved the detection of copy-number variation signals up to 2.3-fold when compared with total cfDNA, with a higher concordance rate with matched osteosarcoma tissue.
Conclusions:
This finding demonstrated the potential of cfDNA size profiling in the stratification of poor prognostic patients with osteosarcoma. The short fragments of cfDNA are a promising source for boosting the detection of significant mutations in osteosarcoma.

See related commentary by Weiser et al., p. 2017
Data from ALK Amplification and Rearrangements Are Recurrent Targetable Events in Congenital and Adult Glioblastoma
Authors: Blandin Anne-Florence , Giglio Ross , Graham Maya Srikanth , Garcia Guadalupe , Malinowski Seth , Woods Jared K. , Ramkissoon Shakti , Ramkissoon Lori , Dubois Frank , Schoolcraft Kathleen , Tsai Jessica , Wang Dayle , Jones Robert , Vogelzang Jayne , Pelton Kristine , Becker Sarah , Watkinson Fiona , Sinai Claire , Cohen Elizabeth F. , Booker Matthew A. , Tolstorukov Michael Y. , Haemels Veerle , Goumnerova Liliana , Wright Karen , Kieran Mark , Fehnel Katie , Reardon David , Tauziede-Espariat Arnault , Lulla Rishi , Carcamo Benjamin , Chaleff Stanley , Charest Alain , De Smet Frederik , Ligon Azra H. , Dubuc Adrian , Pages Melanie , Varlet Pascale , Wen Patrick Y. , Alexander Brian M. , Chi Susan , Alexandrescu Sanda , Kittler Ralf , Bachoo Robert , Bandopadhayay Pratiti , Beroukhim Rameen , Ligon Keith L.
Published: April 2023

AbstractPurpose:
Anaplastic lymphoma kinase (ALK) aberrations have been identified in pediatric-type infant gliomas, but their occurrence across age groups, functional effects, and treatment response has not been broadly established.
Experimental Design:
We performed a comprehensive analysis of ALK expression and genomic aberrations in both newly generated and retrospective data from 371 glioblastomas (156 adult, 205 infant/pediatric, and 10 congenital) with in vitro and in vivo validation of aberrations.
Results:
ALK aberrations at the protein or genomic level were detected in 12% of gliomas (45/371) in a wide age range (0–80 years). Recurrent as well as novel ALK fusions (LRRFIP1–ALK, DCTN1–ALK, PRKD3–ALK) were present in 50% (5/10) of congenital/infant, 1.4% (3/205) of pediatric, and 1.9% (3/156) of adult GBMs. ALK fusions were present as the only candidate driver in congenital/infant GBMs and were sometimes focally amplified. In contrast, adult ALK fusions co-occurred with other oncogenic drivers. No activating ALK mutations were identified in any age group. Novel and recurrent ALK rearrangements promoted STAT3 and ERK1/2 pathways and transformation in vitro and in vivo. ALK-fused GBM cellular and mouse models were responsive to ALK inhibitors, including in patient cells derived from a congenital GBM. Relevant to the treatment of infant gliomas, we showed that ALK protein appears minimally expressed in the forebrain at perinatal stages, and no gross effects on perinatal brain development were seen in pregnant mice treated with the ALK inhibitor ceritinib.
Conclusions:
These findings support use of brain-penetrant ALK inhibitors in clinical trials across infant, pediatric, and adult GBMs.

See related commentary by Mack and Bertrand, p. 2567
Data from Crizotinib Has Preclinical Efficacy in Philadelphia-Negative Myeloproliferative Neoplasms
Authors: Gurska Lindsay M. , Okabe Rachel , Schurer Alexandra , Tong Meng Maxine , Soto Mark , Choi Daniel , Ames Kristina , Glushakow-Smith Shira , Montoya Allison , Tein Ellen , Miles Linde A. , Cheng Haiying , Hankey-Giblin Pamela , Levine Ross L. , Goel Swati , Halmos Balazs , Gritsman Kira
Published: April 2023

AbstractPurpose:
The Philadelphia chromosome–negative myeloproliferative neoplasms (MPN) polycythemia vera, essential thrombocythemia, and primary myelofibrosis are characterized by JAK/STAT pathway activation. JAK inhibitors are approved for MPN treatment, but persistence has been observed, due to JAK/STAT reactivation.
Experimental Design:
Using MPN patient samples, JAK2-mutated cell lines, and MPN mouse models, we examined both the efficacy and mechanism by which crizotinib, the ALK/MET/RON/ROS1 inhibitor approved for the treatment of non–small cell lung cancer, alters MPN cell proliferation and JAK/STAT activation.
Results:
We found that crizotinib suppresses proliferation and activation of JAK/STAT signaling, and decreases the disease burden in the JAK2V617F mouse model of MPN. Furthermore, we found that crizotinib could overcome JAK inhibitor persistence to ruxolitinib. Interestingly, phosphorylation of the crizotinib target RON kinase was enhanced in ruxolitinib-persistent cells. We show that phospho-JAK2 and phospho-RON can physically interact to sustain JAK/STAT signaling, and that the combination of crizotinib and ruxolitinib disrupts this interaction. Furthermore, RON knockdown suppresses proliferation and activation of JAK/STAT signaling in JAK2-mutated cells, and RON deletion in a JAK2V617F mouse MPN model decreases the disease burden. We also observed RON hyperactivation in MPN patient cells, suggesting that RON may be an important target of crizotinib in MPN.
Conclusions:
In summary, we demonstrate that crizotinib has preclinical efficacy in MPN patient cells, JAK2-mutated cell lines, and a JAK2-mutated mouse model, and that the combination of crizotinib with JAK inhibitors suppresses JAK inhibitor persistence. Our work suggests that crizotinib should be investigated for the treatment of patients with MPN.
Supplementary Material from Mesothelin is a malignant factor and therapeutic vaccine target for pancreatic cancer
Authors: Li Min , Bharadwaj Uddalak , Zhang Rongxin , Zhang Sheng , Mu Hong , Fisher William E. , Brunicardi F. Charles , Chen Changyi , Yao Qizhi
Published: April 2023

Supplementary Material from Mesothelin is a malignant factor and therapeutic vaccine target for pancreatic cancer
Supplementary Fig. S2 from Quantitative live imaging of cancer and normal cells treated with Kinesin-5 inhibitors indicates significant differences in phenotypic responses and cell fate
Authors: Orth James D. , Tang Yangzhong , Shi Jade , Loy Clement T. , Amendt Christiane , Wilm Claudia , Zenke Frank T. , Mitchison Timothy J.
Published: April 2023

Supplementary Fig. S2 from Quantitative live imaging of cancer and normal cells treated with Kinesin-5 inhibitors indicates significant differences in phenotypic responses and cell fate
Supplementary Fig. S1 from Bortezomib is ineffective in an orthotopic mouse model of pancreatic adenocarcinoma
Authors: Märten Angela , Zeiss Nina , Serba Susanne , Mehrle Stefan , von Lilienfeld-Toal Marie , Schmidt Jan
Published: April 2023

Supplementary Fig. S1 from Bortezomib is ineffective in an orthotopic mouse model of pancreatic adenocarcinoma
Supplementary Fig. S5 from The G-rich promoter and G-rich coding sequence of basic fibroblast growth factor are the targets of thalidomide in glioma
Authors: Mei Szu-Chieh , Wu Rong-Tsun
Published: April 2023

Supplementary Fig. S5 from The G-rich promoter and G-rich coding sequence of basic fibroblast growth factor are the targets of thalidomide in glioma
Supplementary Table S2 from Identification of a nonkinase target mediating cytotoxicity of novel kinase inhibitors
Authors: Ross-Macdonald Petra , de Silva Heshani , Guo Qi , Xiao Hong , Hung Chen-Yi , Penhallow Becky , Markwalder Jay , He Liqi , Attar Ricardo M. , Lin Tai-an , Seitz Steven , Tilford Charles , Wardwell-Swanson Judith , Jackson Donald
Published: April 2023

Supplementary Table S2 from Identification of a nonkinase target mediating cytotoxicity of novel kinase inhibitors
Supplementary Figure Legend and Methods from Arsenic trioxide decreases AKT protein in a caspase-dependent manner
Authors: Mann Koren K. , Colombo Myrian , Miller Wilson H.
Published: April 2023

Supplementary Figure Legend and Methods from Arsenic trioxide decreases AKT protein in a caspase-dependent manner
Supplemental Table 1 from Gene expression profiling of imatinib and PD166326-resistant CML cell lines identifies Fyn as a gene associated with resistance to BCR-ABL inhibitors
Authors: Grosso Sébastien , Puissant Alexandre , Dufies Maeva , Colosetti Pascal , Jacquel Arnaud , Lebrigand Kevin , Barbry Pascal , Deckert Marcel , Cassuto Jill Patrice , Mari Bernard , Auberger Patrick
Published: April 2023

All significant (p {less than or equal to} 0.05) categories resulting from each list produced the over-represented biological themes shown in supplementary Table 1.
Supplementary Figure 3 from Synthesis and biological analysis of new curcumin analogues bearing an enhanced potential for the medicinal treatment of cancer
Authors: Ohori Hisatsugu , Yamakoshi Hiroyuki , Tomizawa Masaki , Shibuya Masatoshi , Kakudo Yuichi , Takahashi Atsuko , Takahashi Shin , Kato Satoshi , Suzuki Takao , Ishioka Chikashi , Iwabuchi Yoshiharu , Shibata Hiroyuki
Published: April 2023

Supplementary Figure 3 from Synthesis and biological analysis of new curcumin analogues bearing an enhanced potential for the medicinal treatment of cancer
Supplementary Figure 3 from The Mismatch Repair System Modulates Curcumin Sensitivity through Induction of DNA Strand Breaks and Activation of G2-M Checkpoint
Authors: Jiang Zhihua , Jin ShunQian , Yalowich Jack C. , Brown Kevin D. , Rajasekaran Baskaran
Published: April 2023

Supplementary Figure 3 from The Mismatch Repair System Modulates Curcumin Sensitivity through Induction of DNA Strand Breaks and Activation of G2-M Checkpoint
Supplementary Figure 5 from Combination of Two Insulin-Like Growth Factor-I Receptor Inhibitory Antibodies Targeting Distinct Epitopes Leads to an Enhanced Antitumor Response
Authors: Dong Jianying , Demarest Stephen J. , Sereno Arlene , Tamraz Susan , Langley Emma , Doern Adam , Snipas Tracey , Perron Keli , Joseph Ingrid , Glaser Scott M. , Ho Steffan N. , Reff Mitchell E. , Hariharan Kandasamy
Published: April 2023

Supplementary Figure 5 from Combination of Two Insulin-Like Growth Factor-I Receptor Inhibitory Antibodies Targeting Distinct Epitopes Leads to an Enhanced Antitumor Response
Related Editorial from Combination of Two Insulin-Like Growth Factor-I Receptor Inhibitory Antibodies Targeting Distinct Epitopes Leads to an Enhanced Antitumor Response
Authors: Dong Jianying , Demarest Stephen J. , Sereno Arlene , Tamraz Susan , Langley Emma , Doern Adam , Snipas Tracey , Perron Keli , Joseph Ingrid , Glaser Scott M. , Ho Steffan N. , Reff Mitchell E. , Hariharan Kandasamy
Published: April 2023

Related Editorial from Combination of Two Insulin-Like Growth Factor-I Receptor Inhibitory Antibodies Targeting Distinct Epitopes Leads to an Enhanced Antitumor Response
Supplementary Data from HYD1-induced increase in reactive oxygen species leads to autophagy and necrotic cell death in multiple myeloma cells
Authors: Nair Rajesh R. , Emmons Michael F. , Cress Anne E. , Argilagos Raul F. , Lam Kit , Kerr William T. , Wang Hong-Gong , Dalton William S. , Hazlehurst Lori A.
Published: April 2023

Supplementary Data from HYD1-induced increase in reactive oxygen species leads to autophagy and necrotic cell death in multiple myeloma cells
Supplementary Figure 1 from γ-Tocotrienol Promotes TRAIL-Induced Apoptosis through Reactive Oxygen Species/Extracellular Signal-Regulated Kinase/p53–Mediated Upregulation of Death Receptors
Authors: Kannappan Ramaswamy , Ravindran Jayaraj , Prasad Sahdeo , Sung Bokyung , Yadav Vivek R. , Reuter Simone , Chaturvedi Madan M. , Aggarwal Bharat B.
Published: April 2023

Supplementary Figure 1 from γ-Tocotrienol Promotes TRAIL-Induced Apoptosis through Reactive Oxygen Species/Extracellular Signal-Regulated Kinase/p53–Mediated Upregulation of Death Receptors
Supplementary Figure 1 from Effects of Src kinase inhibition induced by dasatinib in non–small cell lung cancer cell lines treated with cisplatin
Authors: Ceppi Paolo , Papotti Mauro , Monica Valentina , Iacono Marco Lo , Saviozzi Silvia , Pautasso Marisa , Novello Silvia , Mussino Stefano , Bracco Enrico , Volante Marco , Scagliotti Giorgio V.
Published: April 2023

Supplementary Figure 1 from Effects of Src kinase inhibition induced by dasatinib in non–small cell lung cancer cell lines treated with cisplatin
Supplementary Figure 1 from Gene Expression Signatures as a Guide to Treatment Strategies for In-Transit Metastatic Melanoma
Authors: Augustine Christina K. , Jung Sin-Ho , Sohn Insuk , Yoo Jin Soo , Yoshimoto Yasunori , Olson John A. , Friedman Henry S. , Ali-Osman Francis , Tyler Douglas S.
Published: April 2023

Supplementary Figure 1 from Gene Expression Signatures as a Guide to Treatment Strategies for In-Transit Metastatic Melanoma
Supplementary Fig. S3 from The antitumor properties of a nontoxic, nitric oxide–modified version of saquinavir are independent of Akt
Authors: Maksimovic-Ivanic Danijela , Mijatovic Sanja , Miljkovic Djordje , Harhaji-Trajkovic Ljubica , Timotijevic Gordana , Mojic Marija , Dabideen Darrin , Cheng Kai Fan , McCubrey James A. , Mangano Katia , Al-Abed Yousef , Libra Massimo , Garotta Gianni , Stosic-Grujicic Stanislava , Nicoletti Ferdinando
Published: April 2023

Supplementary Fig. S3 from The antitumor properties of a nontoxic, nitric oxide–modified version of saquinavir are independent of Akt
Supplementary Fig. S3 from Preclinical evaluation of synergistic effect of telomerase-specific oncolytic virotherapy and gemcitabine for human lung cancer
Authors: Liu Dong , Kojima Toru , Ouchi Masaaki , Kuroda Shinji , Watanabe Yuichi , Hashimoto Yuuri , Onimatsu Hideki , Urata Yasuo , Fujiwara Toshiyoshi
Published: April 2023

Supplementary Fig. S3 from Preclinical evaluation of synergistic effect of telomerase-specific oncolytic virotherapy and gemcitabine for human lung cancer
Supplementary Data from Demonstration of the equivalent pharmacokinetic/pharmacodynamic dosing strategy in a multiple-dose study of gefitinib
Authors: Wang Shining , Zhou Qingyu , Gallo James M.
Published: April 2023

Supplementary Data from Demonstration of the equivalent pharmacokinetic/pharmacodynamic dosing strategy in a multiple-dose study of gefitinib
Adobe PDF - Supplementary_Data.pdf from Preclinical Evaluation of Nilotinib Efficacy in an Imatinib-Resistant KIT-Driven Tumor Model
Authors: Cullinane Carleen , Natoli Anthony , Hui Yorlon , Conus Nelly , Jackson Susan , Brüggen Joseph , Manley Paul W. , McArthur Grant A.
Published: April 2023

Adobe PDF - Supplementary_Data.pdf from Preclinical Evaluation of Nilotinib Efficacy in an Imatinib-Resistant KIT-Driven Tumor Model
Supplementary Figure 4 from Improved low molecular weight Myc-Max inhibitors
Authors: Wang Huabo , Hammoudeh Dalia I. , Follis Ariele Viacava , Reese Brian E. , Lazo John S. , Metallo Steven J. , Prochownik Edward V.
Published: April 2023

Supplementary Figure 4 from Improved low molecular weight Myc-Max inhibitors
Supplementary Figure 1 from Essential role of mitochondria in apoptosis of cancer cells induced by the marine alkaloid Lamellarin D
Authors: Ballot Caroline , Kluza Jérome , Martoriati Alain , Nyman Ulrika , Formstecher Pierre , Joseph Bertrand , Bailly Christian , Marchetti Philippe
Published: April 2023

Supplementary Figure 1 from Essential role of mitochondria in apoptosis of cancer cells induced by the marine alkaloid Lamellarin D
Supplementary Figure 3 from Overexpression of GRIM-19 in Cancer Cells Suppresses STAT3-Mediated Signal Transduction and Cancer Growth
Authors: Okamoto Takashi , Inozume Takashi , Mitsui Hiroshi , Kanzaki Mirei , Harada Kazutoshi , Shibagaki Naotaka , Shimada Shinji
Published: April 2023

Supplementary Figure 3 from Overexpression of GRIM-19 in Cancer Cells Suppresses STAT3-Mediated Signal Transduction and Cancer Growth
Supplementary Fig. S3B from DZNep is a global histone methylation inhibitor that reactivates developmental genes not silenced by DNA methylation
Authors: Miranda Tina Branscombe , Cortez Connie C. , Yoo Christine B. , Liang Gangning , Abe Masanobu , Kelly Theresa K. , Marquez Victor E. , Jones Peter A.
Published: April 2023

Supplementary Fig. S3B from DZNep is a global histone methylation inhibitor that reactivates developmental genes not silenced by DNA methylation
Supplementary Figure 1 from The Novel Tryptamine Derivative JNJ-26854165 Induces Wild-Type p53- and E2F1-Mediated Apoptosis in Acute Myeloid and Lymphoid Leukemias
Authors: Kojima Kensuke , Burks Jared K. , Arts Janine , Andreeff Michael
Published: April 2023

Supplementary Figure 1 from The Novel Tryptamine Derivative JNJ-26854165 Induces Wild-Type p53- and E2F1-Mediated Apoptosis in Acute Myeloid and Lymphoid Leukemias
Supplementary Data from Bridging the Gap between Cytotoxic and Biologic Therapy with Metronomic Topotecan and Pazopanib in Ovarian Cancer
Authors: Merritt William M. , Nick Alpa M. , Carroll Amy R. , Lu Chunhua , Matsuo Koji , Dumble Melissa , Jennings Nicholas , Zhang ShuYun , Lin Yvonne G. , Spannuth Whitney A. , Kamat Aparna A. , Stone Rebecca L. , Shahzad Mian M.K. , Coleman Robert L. , Kumar Rakesh , Sood Anil K.
Published: April 2023

Supplementary Data from Bridging the Gap between Cytotoxic and Biologic Therapy with Metronomic Topotecan and Pazopanib in Ovarian Cancer
Supplementary Figure Legend 1 from Hyaluronan Inhibits Postchemotherapy Tumor Regrowth in a Colon Carcinoma Xenograft Model
Authors: Mueller Barbara M. , Schraufstatter Ingrid U. , Goncharova Valentina , Povaliy Tatiana , DiScipio Richard , Khaldoyanidi Sophia K.
Published: April 2023

Supplementary Figure Legend 1 from Hyaluronan Inhibits Postchemotherapy Tumor Regrowth in a Colon Carcinoma Xenograft Model
Supplementary Table S1 from Modulation of the expression of the invasion-suppressor CRMP-1 by cyclooxygenase-2 inhibition via reciprocal regulation of Sp1 and C/EBPα
Authors: Wu Cheng-Chung , Lin Jau-Chen , Yang Shuenn-Chen , Lin Chiu-Wen , Chen Jeremy J.W. , Shih Jin-Yuan , Hong Tse-Ming , Yang Pan-Chyr
Published: April 2023

Supplementary Table S1 from Modulation of the expression of the invasion-suppressor CRMP-1 by cyclooxygenase-2 inhibition via reciprocal regulation of Sp1 and C/EBPα
Data from SUMOylation of HMGA2: selective destabilization of promyelocytic leukemia protein via proteasome
Authors: Cao Xuefei , Clavijo Carlos , Li Xu , Lin H. Helen , Chen Yuan , Shih Hsiu-Ming , Ann David K.
Published: April 2023

Abstract
The HMGA2 architectural protein functions in a variety of cellular processes, such as cell growth, transcription regulation, neoplastic transformation, and progression. Up-regulation of HMGA2 protein is observed in many tumors and is associated with advanced cancers with poor prognoses. Although the expression and biochemical properties of HMGA2 protein are regulated by microRNA and phosphorylation, it is unknown whether HMGA2 activity can also be regulated by SUMOylation, and that is what is investigated in this report. We identified HMGA2 as a SUMOylation target and showed that the expression of wild-type HMGA2, but not SUMOylation-defective HMGA2(2K/R), selectively lowered the steady-state level of PML protein. Consequently, the HMGA2-elicited PML down-regulation rendered a reduction in the average number of PML nuclear bodies per cell and the volume of PML assembled per PML nuclear body. Using small interfering RNA to suppress endogenous ubiquitin expression and proteasome inhibitor to repress ubiquitin-mediated protein degradation, we showed that HMGA2 confers PML down-regulation through ubiquitin-proteasome–dependent protein degradation. Importantly, arsenic trioxide treatment stimulated HMGA2 SUMOylation, leading to the formation of HMGA2 nuclear foci surrounding PML nuclear bodies and the stimulation of PML degradation. Collectively, our results unveil a previously unrecognized effect by HMGA2 on the modulation of PML protein level, providing a novel mechanism underlying HMGA2 function and underscoring the molecular basis for oncogenic progression by HMGA2. [Mol Cancer Ther 2008;7(4):923–34]
Data from Celecoxib Can Induce Vascular Endothelial Growth Factor Expression and Tumor Angiogenesis
Authors: Xu Kaiming , Gao Huiying , Shu Hui-Kuo G.
Published: April 2023

Abstract
Increased COX-2 expression has been linked to increased angiogenesis and a worse prognosis in patients with malignant gliomas and other tumor types. This led to our interest in assessing the response of glioma cell lines to treatment with celecoxib, a selective COX-2 inhibitor. However, contrary to its reported antiangiogenic effects, treatment with celecoxib actually induced the expression of VEGF in multiple glioma as well as other cancer cell lines. This induction of VEGF was comparable to, if not greater than, that found after exposure of cells to hypoxia. Pharmacologic inhibition and siRNA silencing of p38-mitogen-activated protein kinase and the Sp1 transcription factor revealed their involvement in this celecoxib-induced VEGF expression. Consistent with the documented role of Sp1 in this effect, VEGF induction was found to involve transcriptional activation and not to change the stability of VEGF mRNA. The biological significance of this effect was confirmed in vivo by showing both induction of VEGF expression and microvessel density in tumor xenografts and increased angiogenesis in a matrigel plug assay in nude mice that were administered celecoxib. We speculate that treatment with celecoxib may, in some instances, enhance tumor cell expression of VEGF as well as angiogenesis and, consequently, may have detrimental effects on the response of tumors to this drug. Mol Cancer Ther; 10(1); 138–47. ©2011 AACR.
Data from Apogossypol derivatives as antagonists of antiapoptotic Bcl-2 family proteins
Authors: Wei Jun , Kitada Shinichi , Rega Michele F. , Emdadi Aras , Yuan Hongbin , Cellitti Jason , Stebbins John L. , Zhai Dayong , Sun Jiazhi , Yang Li , Dahl Russell , Zhang Ziming , Wu Bainan , Wang Si , Reed Tyler A. , Lawrence Nicholas , Sebti Said , Reed John C. , Pellecchia Maurizio
Published: April 2023

Abstract
Guided by a combination of nuclear magnetic resonance binding assays and computational docking studies, we synthesized a library of 5,5′ substituted Apogossypol derivatives as potent Bcl-XL antagonists. Each compound was subsequently tested for its ability to inhibit Bcl-XL in an in vitro fluorescence polarization competition assay and exert single-agent proapoptotic activity in human cancer cell lines. The most potent compound BI79D10 binds to Bcl-XL, Bcl-2, and Mcl-1 with IC50 values of 190, 360, and 520 nmol/L, respectively, and potently inhibits cell growth in the H460 human lung cancer cell line with an EC50 value of 680 nmol/L, expressing high levels of Bcl-2. BI79D10 also effectively induces apoptosis of the RS11846 human lymphoma cell line in a dose-dependent manner and shows little cytotoxicity against bax−/−bak−/− mouse embryonic fibroblast cells, in which antiapoptotic Bcl-2 family proteins lack a cytoprotective phenotype, implying that BI79D10 has little off-target effects. BI79D10 displays in vivo efficacy in transgenic mice, in which Bcl-2 is overexpressed in splenic B cells. Together with its improved plasma and microsomal stability relative to Apogossypol, BI79D10 represents a lead compound for the development of novel apoptosis-based therapies for cancer. [Mol Cancer Ther 2009;8(4):904–13]
Data from Docetaxel-Resistant Prostate Cancer Cells Remain Sensitive to S-Trityl-l-Cysteine–Mediated Eg5 Inhibition
Authors: Wiltshire Carolyn , Singh Babloo L. , Stockley Jacqueline , Fleming Janis , Doyle Brendan , Barnetson Robert , Robson Craig N. , Kozielski Frank , Leung Hing Y.
Published: April 2023

Abstract
Castrate-resistant prostate cancer remains a major clinical challenge. Due to the toxicity profile of taxane-based chemotherapy and treatment failure in some patients, novel agents with improved efficacy to side effect profiles are urgently needed. Eg5, a member of the kinesin-5 family, controls the formation of the bipolar spindle during cell division, and suppressed Eg5 function leads to mitotic arrest. S-Trityl-l-cysteine (STLC) is a novel Eg5-specific small-molecule inhibitor. Here, we report the first study to evaluate its use in prostate cancer. In a panel of prostate cancer cells, LNCaP and PC3 cells were the most and least sensitive to STLC treatment, with a 7.2-fold difference in their respective GI50 values: 250 nmol/L and 1.8 μmol/L. In LNCaP cells, treatment with either STLC or docetaxel resulted in transient G2-M arrest and subsequent caspase-mediated cell death. However, STLC- and docetaxel-treated PC3M cells have distinct fates: STLC induced a transient G2-M arrest, followed by polyploidy; in contrast, docetaxel-treated PC3M cells progressed to apoptosis after a transient G2-M arrest. Docetaxel-resistant LNCaP-derived (LDocR) cells respond to STLC in a similar manner to the parental cells. Although the docetaxel-resistant PC3M-derived (PDocR) cell line and its parental PC3M cells have similar GI50 to STLC treatment, PDocR cells showed significantly more G2-M arrest and less apoptosis. Hence, although docetaxel-resistant prostate cancer cells remain responsive to Eg5 inhibition with STLC, there are key differences at the cell cycle level, which may have implication in future development. Mol Cancer Ther; 9(6); 1730–9. ©2010 AACR.
Data from Escape from hsa-miR-519c enables drug-resistant cells to maintain high expression of ABCG2
Authors: To Kenneth K.W. , Robey Robert W. , Knutsen Turid , Zhan Zhirong , Ried Thomas , Bates Susan E.
Published: April 2023

Abstract
Overexpression of ABCG2 has been reported in cell lines selected for drug resistance and it is widely believed to be important in the clinical pharmacology of anticancer drugs. We and others have previously identified and validated two microRNAs (miRNA; hsa-miR-519c and hsa-miR-520h) targeting ABCG2. In this study, the shortening of the ABCG2 3′ untranslated region (3′UTR) was found to be a common phenomenon in several ABCG2-overexpressing resistant cell lines, which as a result removes the hsa-miR-519c binding site and its repressive effects on mRNA stability and translation blockade, thereby contributing to drug resistance. On the other hand, reduced expression of hsa-miR-520h, previously thought to have allowed ABCG2 overexpression, was found to be caused by the sequestering of the miRNA by the highly expressed ABCG2. In drug-sensitive cells, inhibitors against hsa-miR-519c and hsa-miR-520h could augment the cytotoxic effect of mitoxantrone, suggesting a substantial role for both miRNAs in controlling ABCG2 level and thereby anticancer drug response. However, in drug-resistant cells, altering the levels of the two miRNAs did not have any effect on sensitivity to mitoxantrone. Taken together, these studies suggest that in ABCG2-overexpressing drug-resistant cells, hsa-miR-519c is unable to affect ABCG2 expression because the mRNA lacks its binding site, whereas hsa-miR-520h is sequestered and unable to limit ABCG2 expression. Given the recent observation that a truncated 3′UTR is also observed in ABCG2-overexpressing human embryonic stem cells, our results in drug-resistant cell lines suggest that 3′UTR truncation is a relatively common mechanism of ABCG2 regulation. [Mol Cancer Ther 2009;8(10):2959–68]