Selected Articles from This Issue.
Authors: PMID: 32060104 [PubMed - in process] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - February 15, 2020 Category: Cancer & Oncology Tags: Clin Cancer Res Source Type: research

The DNA cytosine deaminase APOBEC3B is a molecular determinant of platinum responsiveness in clear cell ovarian cancer.
CONCLUSIONS: These studies demonstrate that APOBEC3B is overexpressed in a subset of CCOC and, contrary to initial expectations, associated with improved (not worse) clinical outcomes. A likely molecular explanation is that DNA damage caused APOBEC3B sensitizes cells to additional genotoxic stress by cisplatin. Thus, APOBEC3B is a molecular determinant and a candidate predictive biomarker of the therapeutic response to platinum-based chemotherapy. These findings may have broader translational relevance, as APOBEC3B is overexpressed in many different cancer types. PMID: 32060098 [PubMed - as supplied by publisher] (Sou...
Source: Clinical Cancer Research - February 14, 2020 Category: Cancer & Oncology Authors: Harris RS, Serebrenik AA, Argyris P, Jarvis MC, Brown WL, Bazzaro M, Vogel RI, Erickson BK, Lee SH, Goergen KM, Maurer MJ, Oberg AL, Hou X, Weroha SJ, Kaufmann SH, Huang Y, Heinzen EP Tags: Clin Cancer Res Source Type: research

Routine-dose and High-dose Icotinib in Advanced Non-Small Cell Lung Cancer Patients harboring EGFR Exon 21 L858R Mutation: the Randomized, Phase II, INCREASE Trial.
CONCLUSIONS: High-dose icotinib improved mPFS and ORR in NSCLC patients harboring 21-L858R mutation with acceptable tolerability, which could be a new therapeutic option for this patient population. PMID: 32060099 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - February 14, 2020 Category: Cancer & Oncology Authors: Li X, Zhang L, Jiang D, Wang Y, Zang A, Ding C, Zhao M, Su W, Zhang Y, Zhong D, Wu J, Zhang C, An G, Hu X, Cheng G, Wang H, Li Y, He X, Liu J, Liang L, Ding L, Mao L, Zhang S Tags: Clin Cancer Res Source Type: research

The immune microenvironment and neoantigen landscape of aggressive salivary gland carcinomas differ by subtype.
CONCLUSIONS: These findings provide new insights into the immune microenvironment and neoantigen landscape of SGCs, showing that mechanisms of immune escape appear to differ by histology. These data nominate potential immunologic vulnerabilities and may help guide the next steps of investigation in precision immunotherapy for these difficult-to-treat cancers. PMID: 32060100 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - February 14, 2020 Category: Cancer & Oncology Authors: Morris LG, Linxweiler M, Kuo F, Katabi N, Nadeem Z, Dalin MG, Makarov V, Chowell D, Dogan S, Ganly I, Hakimi AA, Wong RJ, Riaz N, Ho AL, Chan TA, Lee M Tags: Clin Cancer Res Source Type: research

Single cell genomic characterization reveals the cellular reprogramming of the gastric tumor microenvironment.
CONCLUSIONS: Single-cell gene expression studies revealed widespread reprogramming across multiple cellular elements in the GC TME. Cellular remodeling was delineated by changes in cell numbers, transcriptional states and inter-cellular interactions. This characterization facilitates understanding of tumor biology and enables identification of novel targets including for immunotherapy. PMID: 32060101 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - February 14, 2020 Category: Cancer & Oncology Authors: Sathe A, Grimes SM, Lau BT, Chen J, Suarez C, Huang RJ, Poultsides GA, Ji HP Tags: Clin Cancer Res Source Type: research

Translating basic science discoveries into improved outcomes for glioblastoma.
Abstract Members of the scientific and clinical neuro-oncology community met in April 2019 to discuss the current challenges and opportunities associated with translating basic science discoveries in glioblastoma to improved survival for patients. A summary of key points of these discussions is presented in this report. PMID: 32060102 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - February 14, 2020 Category: Cancer & Oncology Authors: Dirks PB, Gilbert MR, Holland EC, Maher EA, Weiss WA Tags: Clin Cancer Res Source Type: research

Early mortality of brain cancer patients and its connection to cytomegalovirus reactivation during radiochemotherapy.
CONCLUSIONS: For brain cancer patients, HCMV-reactivation after the start of radiochemotherapy is a frequent risk for cognitively detrimental but treatable encephalopathy and premature death. Routinely performed HCMV-diagnostics, assessing basophil counts and study-based anti-viral regimens are necessary to combat this hidden threat. PMID: 32060103 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - February 14, 2020 Category: Cancer & Oncology Authors: Goerig NL, Frey B, Korn K, Fleckenstein B, Überla K, Schmidt MA, Dörfler A, Engelhorn T, Eyüpoglu I, Rühle PF, Putz F, Semrau S, Gaipl US, Fietkau R Tags: Clin Cancer Res Source Type: research

5-Azacitidine Induces NOXA to Prime AML Cells for Venetoclax-mediated Apoptosis.
CONCLUSIONS: These data provide a novel non-epigenetic mechanism of action for 5-Aza and its combinatorial activity with venetoclax through the ISR-mediated induction of PMAIP1. PMID: 32054729 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - February 13, 2020 Category: Cancer & Oncology Authors: Jin S, Cojocari D, Purkal JJ, Popovic R, Talaty NN, Xiao Y, Solomon LR, Boghaert ER, Leverson JD, Phillips DC Tags: Clin Cancer Res Source Type: research

A Phase 2 Trial of Five-Day Neoadjuvant Radiation Therapy for Patients with High-Risk Primary Soft Tissue Sarcoma.
CONCLUSIONS: A shorter five-day neoadjuvant RT regimen results in favorable rates of wound complications and grade ≥2 toxicity after two years follow-up. Five-day RT significantly increased utilization of neoadjuvant RT at our high-volume sarcoma center. With further validation, a putative germline biomarker for wound complications may guide safer RT utilization. PMID: 32054730 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - February 13, 2020 Category: Cancer & Oncology Authors: Kalbasi A, Kamrava M, Chu FI, Telesca D, Van Dams R, Yang Y, Ruan D, Nelson SD, Dry S, Hernandez J, Chmielowski B, Singh AS, Bukata SV, Bernthal N, Steinberg ML, Weidhaas JB, Eilber FC Tags: Clin Cancer Res Source Type: research

Pharmacodynamic analysis of BTK inhibition in patients with chronic lymphocytic leukemia treated with acalabrutinib.
CONCLUSIONS: Higher BTK occupancy was achieved with twice daily over once daily dosing, resulting in deeper and more sustained inhibition of BCR signaling. PMID: 32054731 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - February 13, 2020 Category: Cancer & Oncology Authors: Alsadhan A, Cheung J, Gulrajani M, Gaglione EM, Nierman P, Hamdy A, Izumi R, Bibikova E, Patel P, Sun C, Covey T, Herman SEM, Wiestner A Tags: Clin Cancer Res Source Type: research

What is the real impact of estrogen receptor status on the prognosis and treatment of HER2-positive early breast cancer?
art M Abstract HER2+ early breast cancer is a heterogeneous disease, comprising all the intrinsic breast cancer subtypes. The only biomarker available nowadays for anti-HER2 treatment selection is HER2 status itself, but estrogen receptor (ER) status is emerging as a robust predictive marker within HER2+ disease. In this Perspective, we discuss the biological and clinical differences between patients with HER2+/ER positive (ER+) disease versus those with HER2+/ER negative (ER-neg) tumors, namely short- and long-term (>5 years after diagnosis) prognosis, response to neoadjuvant treatment and benefit from adjuvan...
Source: Clinical Cancer Research - February 11, 2020 Category: Cancer & Oncology Authors: Brandão M, Caparica R, Malorni L, Prat A, Carey LA, Piccart M Tags: Clin Cancer Res Source Type: research

Pathological complete response after neoadjuvant chemotherapy and impact on breast cancer recurrence and survival: a comprehensive meta-analysis.
Abstract PURPOSE: While various studies have highlighted the prognostic significance of pathological complete response (pCR) after neoadjuvant chemotherapy (NAT), the impact of additional adjuvant therapy after pCR is not known. EXPERIMENTAL DESIGN: PubMed was searched for studies with NAT for breast cancer and individual patient-level data was extracted for analysis using plot digitizer software. Hazard ratios (HRs), with 95% probability intervals (PIs), measuring the association between pCR and overall survival (OS) or event-free survival (EFS), were estimated using Bayesian piecewise-exponential proportion...
Source: Clinical Cancer Research - February 11, 2020 Category: Cancer & Oncology Authors: Spring LM, Fell G, Arfe A, Sharma C, Greenup RA, Reynolds KL, Smith BL, Alexander BM, Moy B, Isakoff SJ, Parmigiani G, Trippa L, Bardia A Tags: Clin Cancer Res Source Type: research

Circulating tumor DNA analysis to assess risk of progression after long-term response to PD-(L)1 blockade in NSCLC.
H, Gojenola L, Wakelee HA, Padda SK, Neal JW, Chaft JE, Kris MG, Rudin CM, Merghoub T, Li BT, Alizadeh AA, Diehn M Abstract PURPOSE: Treatment with PD-(L)1 blockade can produce remarkably durable responses in non-small cell lung cancer (NSCLC) patients. However, a significant fraction of long-term responders ultimately progress and predictors of late progression are unknown. We hypothesized that circulating tumor DNA (ctDNA) analysis of long-term responders to PD-(L)1 blockade may differentiate those who will achieve ongoing benefit from those at risk of eventual progression. EXPERIMENTAL DESIGN: In patients ...
Source: Clinical Cancer Research - February 11, 2020 Category: Cancer & Oncology Authors: Hellmann MD, Nabet BY, Rizvi H, Chaudhuri AA, Wells DK, Dunphy MP, Chabon JJ, Liu CL, Hui AB, Arbour KC, Luo J, Preeshagul IR, Moding EJ, Almanza D, Bonilla RF, Sauter JL, Choi H, Tenet M, Abu-Akeel M, Plodkowski AJ, Perez-Johnston R, Yoo CH, Ko RB, Stehr Tags: Clin Cancer Res Source Type: research

Radiotherapy and immunotherapy for cancer: From "systemic" to "multi-site".
Radiotherapy and immunotherapy for cancer: From "systemic" to "multi-site". Clin Cancer Res. 2020 Feb 11;: Authors: Arina A, Gutiontov SI, Weichselbaum RR Abstract In the era of cancer immunotherapy, there is a high interest in combining conventional cancer therapies such as radiotherapy with drugs that stimulate the immune system. The observation that ionizing radiation applied to mouse tumors could delay the growth of distant lesions ("abscopal effect") and this was potentiated by immunostimulatory drugs, led to clinical trials in which often only one lesion was irradia...
Source: Clinical Cancer Research - February 11, 2020 Category: Cancer & Oncology Authors: Arina A, Gutiontov SI, Weichselbaum RR Tags: Clin Cancer Res Source Type: research

BRAF-mutant Transcriptional Subtypes Predict Outcome of Combined BRAF, MEK, and EGFR Blockade with Dabrafenib, Trametinib, and Panitumumab in Patients with Colorectal Cancer.
CONCLUSIONS: BM subtype is significantly associated with the outcome of combination dabrafenib, trametinib, and panitumumab therapy and may serve as a standalone predictive biomarker beyond mutational status. Our findings support a more nuanced approach to targeted therapeutic decisions that incorporates assessment of transcriptional context. PMID: 32047001 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - February 11, 2020 Category: Cancer & Oncology Authors: Middleton G, Yang Y, Campbell CD, André T, Atreya CE, Schellens JHM, Yoshino T, Bendell JC, Hollebecque A, McRee AJ, Siena S, Gordon MS, Tabernero J, Yaeger R, O'Dwyer PJ, De Vos F, Van Cutsem E, Millholland JM, Brase JC, Rangwala F, Gasal E, Corcoran RB Tags: Clin Cancer Res Source Type: research

Kdm6a deficiency activates inflammatory pathways, promotes M2 macrophage polarization, and causes bladder cancer in cooperation with p53 dysfunction.
CONCLUSIONS: Our findings provide insights into multistep carcinogenic processes of BC and suggest molecular targeted therapeutic approaches for BC patients with Kdm6a dysfunction. PMID: 32047002 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - February 11, 2020 Category: Cancer & Oncology Authors: Kobatake K, Ikeda K, Nakata Y, Yamasaki N, Ueda T, Kanai A, Sentani K, Sera Y, Hayashi T, Koizumi M, Miyakawa Y, Inaba T, Sotomaru Y, Kaminuma O, Ichinohe T, Honda ZI, Yasui W, Horie S, Black PC, Matsubara A, Honda H Tags: Clin Cancer Res Source Type: research

Rindopepimut with Bevacizumab for Patients with Relapsed EGFRvIII-Expressing Glioblastoma (ReACT): Results of a Double-Blind Randomized Phase II Trial.
ors Abstract PURPOSE: Rindopepimut is a vaccine targeting the tumor-specific EGF driver mutation, EGFRvIII. The ReACT study investigated whether the addition of rindopepimut to standard bevacizumab improved outcome for patients with relapsed, EGFRvIII-positive glioblastoma. PATIENTS AND METHODS: In this double-blind, randomized, phase II study (NCT01498328) conducted at 26 hospitals in the United States, bevacizumab-naïve patients with recurrent EGFRvIII-positive glioblastoma were randomized to receive rindopepimut or a control injection of keyhole limpet hemocyanin, each concurrent with bevacizumab. The...
Source: Clinical Cancer Research - February 7, 2020 Category: Cancer & Oncology Authors: Reardon DA, Desjardins A, Vredenburgh JJ, O'Rourke DM, Tran DD, Fink KL, Nabors LB, Li G, Bota DA, Lukas RV, Ashby LS, Duic JP, Mrugala MM, Cruickshank S, Vitale L, He Y, Green JA, Yellin MJ, Turner CD, Keler T, Davis TA, Sampson JH, ReACT trial investiga Tags: Clin Cancer Res Source Type: research

Molecular mechanisms of acquired resistance to MET tyrosine kinase inhibitors in patients with MET exon 14 mutant NSCLC.
CONCLUSIONS: On-target secondary mutations and activation of bypass signaling drive resistance to MET TKIs. A deeper understanding of these molecular mechanisms can support the development of sequential or combinatorial therapeutic strategies to overcome resistance. PMID: 32034073 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - February 7, 2020 Category: Cancer & Oncology Authors: Recondo G, Bahcall M, Spurr LF, Che J, Ricciuti B, Leonardi GC, Lo YC, Li YY, Lamberti G, Nguyen T, Milan MSD, Venkatraman D, Umeton R, Paweletz CP, Albayrak A, Cherniack AD, Price KS, Fairclough SR, Nishino M, Sholl LM, Oxnard GR, Janne PA, Awad MM Tags: Clin Cancer Res Source Type: research

Results of the ADAPT phase 3 study of Rocapuldencel-T in combination with sunitinib as first-line therapy in patients with metastatic renal cell carcinoma.
CONCLUSION: Rocapuldencel-T did not improve OS in patients treated with combination therapy, although the immune response correlated with OS. Moreover, we identified two potential survival-predictive biomarkers for patients receiving DC based immuno-therapy, DC vaccine produced IL-12 and higher numbers of T regulatory cells present in the peripheral blood of mRCC patients. PMID: 32034074 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - February 7, 2020 Category: Cancer & Oncology Authors: Figlin RA, Tannir NM, Uzzo RG, Tykodi SS, Chen DYT, Master V, Kapoor A, Vaena D, Lowrance WT, DeBenedette M, Gamble A, Plachco A, Norris MS, Horvatinovich J, Tcherepanova IY, Nicolette CA, Wood CG Tags: Clin Cancer Res Source Type: research

In-vivo tracking of adoptively transferred natural killer-cells in rhesus macaques using 89Zirconium-oxine cell labeling and PET imaging.
CONCLUSIONS: These data support translation of this technique to humans to track the distribution of adoptively infused cells and to develop novel techniques to improve immune cell homing to tumor microenvironments. PMID: 32034075 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - February 7, 2020 Category: Cancer & Oncology Authors: Sato N, Stringaris K, Davidson-Moncada JK, Reger R, Adler SS, Dunbar C, Choyke PL, Childs RW Tags: Clin Cancer Res Source Type: research

Routine plasma-based genotyping to comprehensively detect germline, somatic, and reversion BRCA mutations among patients with advanced solid tumors.
CONCLUSIONS: cfDNA NGS identified high rates of therapeutically relevant mutations without foreknowledge of germline or tissue-based testing, including deleterious somatic BRCA1/2 mutations missed by germline testing and reversion mutations that can have important treatment implications. Further research is needed to confirm clinical application of these findings to guide precision medicine approaches for advanced malignancies. PMID: 32034076 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - February 7, 2020 Category: Cancer & Oncology Authors: Vidula N, Rich TA, Sartor O, Yen J, Hardin A, Nance T, Lilly MB, Nezami MA, Patel SP, Carneiro BA, Fan A, Brufksy AM, Parker BA, Bridges BB, Agarwal N, Maughan BL, Raymond VM, Fairclough SR, Lanman RB, Bardia A, Cristofanilli M Tags: Clin Cancer Res Source Type: research

ATP-citrate lyase epigenetically potentiates oxidative phosphorylation to promote melanoma growth and adaptive resistance to MAPK inhibition.
CONCLUSIONS: We demonstrate that ACLY epigenetically potentiates oxidative phosphorylation to promote melanoma growth and MAPK inhibition adaptive resistance. Our study discovers the novel crosstalk between lipogenesis and mitochondrial function in tumor biology, and highlights targeting ACLY as a potent therapeutic approach via simultaneously impairing tumor growth and MAPK inhibition resistance in melanoma. PMID: 32034077 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - February 7, 2020 Category: Cancer & Oncology Authors: Li C, Guo W, Ma J, Yang Y, Guo S, Zhang W, Zhao T, Yi X, Wang H, Wang S, Liu Y, Dai W, Chen X, Shi Q, Wang G, Gao T Tags: Clin Cancer Res Source Type: research

Use of ex vivo patient derived tumor organotypic spheroids to identify combination therapies for HER2mutant non small cell lung cancer.
CONCLUSIONS: The XDOTS platform can be used to evaluate therapies and therapeutic combinations ex vivo using PDX tumors. This approach may accelerate the identification and clinical development of therapies for targets with no or few existing models and/or therapies. PMID: 32034078 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - February 7, 2020 Category: Cancer & Oncology Authors: Ivanova E, Kuraguchi M, Xu M, Portell A, Taus LJ, Diala I, Lalani AS, Choi J, Chambers ES, Li S, Liu S, Chen T, Barbie TU, Oxnard GR, Haworth J, Wong KK, Dahlberg SE, Aref A, Barbie DA, Bahcall M, Paweletz CP, Janne PA Tags: Clin Cancer Res Source Type: research

Not yet another negative trial - ReACTing on recent glioblastoma trials!
Abstract The present ReACT trial provides data from a small randomized controlled vaccination trial that in addition to other recent immunotherapy trials in glioblastoma allows sketching a rational, advanced trial design for the development of (immune)therapies in glioblastoma elaborating on but not restricting to biological monitoring and endpoints. PMID: 32034079 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - February 7, 2020 Category: Cancer & Oncology Authors: Wick W, Wagener RJ Tags: Clin Cancer Res Source Type: research

Propranolol: What is BLOCKing Its Clinical Investigation in Breast Cancer?
Abstract Pre-surgical propranolol modulates biomarkers associated with breast cancer progression. β-adrenergic signaling promotes invasion, epithelial to mesenchymal transition phenotype, and immune cell infiltration into the tumor microenvironment. Blockade of the β-adrenergic receptor signaling with propranolol, along with potential future combinatorial strategies, holds promise for reducing breast cancer progression and metastasis. PMID: 32029438 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - February 6, 2020 Category: Cancer & Oncology Authors: Blaes AH, Domingo-Musibay E, Kalinsky K Tags: Clin Cancer Res Source Type: research

Randomized trial of intermediate-dose cytarabine in induction and consolidation therapy in adults with acute myeloid leukaemia.
CONCLUSIONS: Induction therapy with intermediate-dose cytarabine with daunorubicin and omacetaxine mepesuccinate increases DFS and survival in persons with AML age 15-55 years compared with conventional-dose cytarabine. PMID: 32029439 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - February 6, 2020 Category: Cancer & Oncology Authors: Wei H, Wang Y, Gale RP, Lin D, Zhou C, Liu B, Qiu S, Gu R, Li Y, Zhao X, Wei S, Gong B, Liu K, Gong X, Liu Y, Zhang G, Song Z, Wang Y, Li W, Mi Y, Wang J Tags: Clin Cancer Res Source Type: research

Validation of a Hematopoietic Cell Transplant - Composite Risk (HCT-CR) Model for Post Transplant Survival Prediction in Patients with Hematologic Malignancies.
Abstract PURPOSE: Allogeneic hematopoietic stem cell transplantation (AHCT) outcomes depend on disease and patient characteristics. We previously developed a novel prognostic model, hematopoietic cell transplant composite-risk (HCT-CR) by incorporating the refined disease risk index (DRI-R) and hematopoietic cell transplant - comorbidity/age index (HCT-CI/Age) to predict post-transplant survival in patients with AML and MDS. Here we aimed to validate and prove the generalizability of the HCT-CR model in an independent cohort of patients with hematologic malignancies receiving AHCT. MATERIALS AND METHODS: Data...
Source: Clinical Cancer Research - February 4, 2020 Category: Cancer & Oncology Authors: Ciurea SO, Kongtim P, Hasan O, Ramos Perez JM, Torres J, Rondon G, Champlin RE Tags: Clin Cancer Res Source Type: research

Tumor mutational burden and PTEN alterations as molecular correlates of response to PD-1/L1 blockade in metastatic triple-negative breast cancer.
CONCLUSIONS: Among patients with mTNBC treated with anti-PD-1/L1 therapies, high TMB and PTEN alterations were associated with longer and shorter survival, respectively. These observations warrant validation in larger datasets. PMID: 32019858 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - February 4, 2020 Category: Cancer & Oncology Authors: Barroso-Sousa R, Keenan TE, Pernas S, Exman P, Jain E, Garrido-Castro AC, Hughes ME, Bychkovsky B, Umeton R, Files JL, Lindeman NI, MacConaill LE, Hodi FS, Krop I, Dillon DA, Winer EP, Wagle N, Lin NU, Mittendorf EA, Van Allen EM, Tolaney SM Tags: Clin Cancer Res Source Type: research

Double Trouble: Concomitant RB1 and BRCA2 depletion evokes aggressive phenotypes.
Abstract Coordinate single or two copy loss of BRCA2/RB1 tumor suppressor genes, which reside in close chromosomal proximity, were found to be associated with aggressive prostate cancer and therapeutic resistance. Modeling these events and analyses of human cancers suggest that dual depletion of BRCA2/RB1 may represent a distinct subtype of disease. PMID: 32019859 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - February 4, 2020 Category: Cancer & Oncology Authors: Mandigo AC, Knudsen KE Tags: Clin Cancer Res Source Type: research

Synergistic Combination of Oncolytic Virotherapy and Immunotherapy for Glioma.
CONCLUSIONS: IL15Rα-IL15-armed oncolytic poxviruses provide potent antitumor effects against brain tumors when combined with adoptive T cell therapy, rapamycin and celecoxib. PMID: 32019860 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - February 4, 2020 Category: Cancer & Oncology Authors: Tang B, Guo ZS, Bartlett DL, Yan DZ, Schane CP, Liu J, McFadden G, Thomas DL, Shisler JL, Roy EJ Tags: Clin Cancer Res Source Type: research

Local and Systemic Immune Dysregulation Alters Glioma Growth in Hyperglycemic Mice.
CONCLUSIONS: Hyperglycemia may enhance glioma growth through promotion of RAGE expression and suppression of antitumor immune responses. However, abrogation of the pro-inflammatory milieu in tumors may also dampen the growth of inflammatory glioma subtypes in the brains of diabetic mice. This dichotomy in glioma growth response to hyperglycemia may partly explain why conflicting epidemiological studies show both an increased risk and a protective effect of Db in patients with malignant gliomas. PMID: 32019861 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - February 4, 2020 Category: Cancer & Oncology Authors: Zhang IY, Zhou H, Liu H, Zhang L, Gao H, Liu S, Song Y, Alizadeh D, Yin HH, Pillai RK, Badie B Tags: Clin Cancer Res Source Type: research

Circulating tumor cells and early relapse in node-positive melanoma.
Abstract PURPOSE: There is a need for sensitive, reproducible biomarkers for stage III melanoma patients to guide clinical decision making. Circulating tumor cells (CTCs) can be detected in melanoma patients; however, there is limited data regarding their significance in stage III disease. The aim of this study was to determine if CTCs are associated with early relapse in stage III melanoma. EXPERIMENTAL DESIGN: We prospectively assessed CTCs at first presentation in clinic (baseline) for 243 stage III melanoma patients. CTCs were measured using the CellSearch System. Relapse-free survival (RFS) was compared ...
Source: Clinical Cancer Research - February 3, 2020 Category: Cancer & Oncology Authors: Lucci A, Hall C, Patel SP, Narendran B, Bauldry JB, Royal R, Karhade M, Upshaw JR, Wargo JA, Glitza IC, Wong MKK, Amaria RN, Tawbi HA, Diab A, Davies MA, Gershenwald JE, Lee JE, Hwu P, Ross MI Tags: Clin Cancer Res Source Type: research

Enhancing Chimeric Antigen Receptor T cell Efficacy in Solid Tumors.
tti G Abstract Chimeric antigen receptor (CAR) T cell therapy has been acclaimed as a revolution in cancer treatment following the impressive results in hematological malignancies. Unfortunately, in patients with solid tumors, objectives responses to CAR T cells are still anecdotal, and important issues are driven by on-target but off-tumor activity of CAR T cells and by the extremely complex biology of solid tumors. Here, we will review the recent attempts to challenge the therapeutic impediments to CAR T cell therapy in solid tumors. We will focus on the most promising strategies of antigen targeting to improve ...
Source: Clinical Cancer Research - February 3, 2020 Category: Cancer & Oncology Authors: Fucá G, Reppel L, Landoni E, Savoldo B, Dotti G Tags: Clin Cancer Res Source Type: research

Selected Articles from This Issue.
Authors: PMID: 32014887 [PubMed - in process] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - February 1, 2020 Category: Cancer & Oncology Tags: Clin Cancer Res Source Type: research

Correction: Arming an Oncolytic Herpes Simplex Virus Type 1 with a Single-chain Fragment Variable Antibody against PD-1 for Experimental Glioblastoma Therapy.
PMID: 32014888 [PubMed - in process] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - February 1, 2020 Category: Cancer & Oncology Authors: Passaro C, Alayo Q, DeLaura I, McNulty J, Grauwet K, Ito H, Bhaskaran V, Mineo M, Lawler SE, Shah K, Speranza MC, Goins W, McLaughlin E, Fernandez S, Reardon DA, Freeman GJ, Chiocca EA, Nakashima H Tags: Clin Cancer Res Source Type: research

A Phase I study of safety, pharmacokinetics, and pharmacodynamics of concurrent everolimus and buparlisib treatment in advanced solid tumors.
CONCLUSION: The combination of everolimus and buparlisib is safe and well-tolerated at the RP2D of 5mg and 60mg on a continuous daily schedule. PMID: 32005746 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 31, 2020 Category: Cancer & Oncology Authors: Owonikoko TK, Harvey RD, Carthon B, Chen Z, Lewis C, Collins H, Zhang C, Lawson DH, Alese OB, Bilen MA, Sica GL, Steuer CE, Shaib WL, Wu C, Harris WB, Akce M, Kudchagkar RR, El-Rayes BF, Lonial S, Ramalingam SS, Khuri FR Tags: Clin Cancer Res Source Type: research

Predictive biomarkers for adjuvant capecitabine benefit in early stage triple negative breast cancer in the FinXX clinical trial.
CONCLUSIONS: Genes and metagenes related to anti-tumor immunity, immune response and capecitabine activation could identify TNBC patients who are more likely to benefit from adjuvant capecitabine. Given the reduced power to observe significant findings when correcting for multiplicity, our findings provide the basis for future hypothesis-testing validation studies on larger clinical trials. PMID: 32005747 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 31, 2020 Category: Cancer & Oncology Authors: Asleh K, Brauer HA, Sullivan A, Lauttia S, Lindman H, Nielsen TO, Joensuu H, Thompson EA, Chumsri S Tags: Clin Cancer Res Source Type: research

Gefitinib and afatinib show potential efficacy for Fanconi anemia-related head and neck cancer.
CONCLUSIONS: Our data present a complete preclinical analysis and promising therapeutic line of the first FDA/EMA approved anticancer drugs exerting cancer specific toxicity for HNSCC in FA patients. PMID: 32005748 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 31, 2020 Category: Cancer & Oncology Authors: Montanuy H, Martínez-Barriocanal A, Casado JA, Rovirosa L, Ramírez MJ, Nieto R, Carrascoso-Rubio C, Riera P, Gonzalez A, Lerma E, Lasa A, Carreras-Puigvert J, Helleday T, Bueren JA, Arango D, Minguillón J, Surrallés J Tags: Clin Cancer Res Source Type: research

FDA Approval Summary: Atezolizumab plus paclitaxel protein-bound for the treatment of patients with advanced or metastatic TNBC whose tumors express PD-L1.
Abstract On March 8, 2019, the FDA granted accelerated approval to atezolizumab in combination with paclitaxel protein-bound for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1 (PD-L1 stained tumor-infiltrating immune cells [IC] of any intensity covering ≥ 1% of the tumor area), as determined by an FDA-approved test. Approval was based on data from IMpassion130, which randomized patients to receive atezolizumab or placebo in combination with paclitaxel-protein bound. Investigator-assessed progression-free survival (...
Source: Clinical Cancer Research - January 30, 2020 Category: Cancer & Oncology Authors: Narayan P, Wahby S, Gao JJ, Amiri-Kordestani L, Ibrahim A, Bloomquist E, Tang S, Xu Y, Liu J, Fu W, Song P, King-Kallimanis BL, Hou S, Gong Y, Kalavar S, Ghosh S, Philip R, Goldberg KB, Theoret MR, Blumenthal GM, Kluetz PG, Sridhara R, Pazdur R, Beaver JA Tags: Clin Cancer Res Source Type: research

Exploiting TCR recognition of shared hot-spot oncogene-encoded neoantigens.
M, Melero I Abstract T-cell recognizable p53 hot-spot mutations offer opportunities for immunotherapy and immune monitoring. Recognition of p53 mutations by peripheral blood CD8 and CD4 T lymphocytes has been revealed. PMID: 32001482 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 30, 2020 Category: Cancer & Oncology Authors: Olivera I, Etxeberria I, Bolaños E, Gato-Cañas M, Melero I Tags: Clin Cancer Res Source Type: research

Overcoming adaptive resistance to KRAS inhibitors through vertical pathway targeting.
Abstract KRAS G12C inhibitors have shown promise in KRAS G12C mutant lung cancer but intrinsic and acquired resistance are common. Co-treatment with inhibitors of the protein phosphatase SHP2 can abrogate the adaptive response of cancer cells to KRAS inhibitors resulting in greater suppression of MAPK signaling and enhanced tumor growth inhibition. PMID: 32001483 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 30, 2020 Category: Cancer & Oncology Authors: Yaeger R, Solit DB Tags: Clin Cancer Res Source Type: research

Immune checkpoint blockade in combination with stereotactic body radiotherapy in patients with metastatic pancreatic ductal adenocarcinoma.
CONCLUSIONS: The combination of ICI and SBRT has an acceptable safety profile and demonstrates a modest treatment benefit in patients with metastatic PDAC. PMID: 31996388 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 29, 2020 Category: Cancer & Oncology Authors: Xie C, Duffy A, Brar G, Fioravanti S, Mabry-Hrones D, Walker M, Monge Bonilla C, Wood BJ, Citrin DE, Gil Ramirez EM, Escorcia FE, Redd B, Hernandez JM, Davis JL, Gasmi B, Kleiner D, Steinberg SM, Jones JC, Greten TF Tags: Clin Cancer Res Source Type: research

A Novel GUCY2C-CD3 T cell Engaging Bispecific construct (PF-07062119) for the Treatment of Gastrointestinal Cancers.
CONCLUSION: These data highlight the potential for PF-07062119 to demonstrate efficacy and improve patient outcomes in CRC and other gastrointestinal malignancies. PMID: 31996389 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 29, 2020 Category: Cancer & Oncology Authors: Mathur D, Root AR, Bugaj-Gaweda B, Bisulco S, Tan X, Fang W, Kearney JC, Lucas J, Guffroy M, Golas J, Rohde CM, Stevens C, Kamperschroer C, Kelleher K, Lawrence-Henderson RF, Upeslacis E, Yao J, Narula J, LaVallie ER, Fernandez DR, Buetow BS, Rosfjord E, Tags: Clin Cancer Res Source Type: research

Antigen Experienced T Cells from Peripheral Blood Recognize p53 Neoantigens.
CONCLUSIONS: PBL was a noninvasive source of T cells targeting TP53 mutations for cell therapy and can provide a window into intratumoral p53 neoantigen immune responses. PMID: 31996390 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 29, 2020 Category: Cancer & Oncology Authors: Malekzadeh P, Yossef R, Cafri G, Paria BC, Lowery FJ, Jafferji M, Good ML, Sachs A, Copeland AR, Kim SP, Kivitz S, Parkhurst MR, Robbins PF, Ray S, Xi L, Raffeld M, Yu Z, Restifo NP, Somerville RPT, Rosenberg SA, Deniger DC Tags: Clin Cancer Res Source Type: research

Predicted Prognosis of Pancreatic Cancer Patients by Machine Learning.
CONCLUSIONS: Analysis of epigenetic changes in mucin genes may be of diagnostic utility and one of the prognostic predictors for patients with pancreatic ductal adenocarcinoma. PMID: 31992588 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 28, 2020 Category: Cancer & Oncology Authors: Yokoyama S, Hamada T, Higashi M, Matsuo K, Maemura K, Kurahara H, Horinouchi M, Hiraki T, Sugimoto T, Akahane T, Yonezawa S, Kornmann M, Batra SK, Hollingsworth MA, Tanimoto A Tags: Clin Cancer Res Source Type: research

Phase II Trial of Cabozantinib in Recurrent/Metastatic Endometrial Cancer: A Study of the Princess Margaret, Chicago and California Consortia (NCI9322/PHL86).
CONCLUSIONS: Cabozantinib has activity in serous and endometrioid histology EC. These results support further evaluation in genomically characterized patient cohorts. PMID: 31992589 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 28, 2020 Category: Cancer & Oncology Authors: Dhani NC, Hirte HW, Wang L, Burnier JV, Jain A, Butler MO, Welch S, Fleming GF, Hurteau J, Matsuo K, Matei D, Jimenez W, Johnston C, Cristea M, Tonkin K, Ghatage P, Lheureux S, Mehta A, Quintos J, Tan Q, Kamel-Reid S, Ludkovski O, Tsao MS, Wright JJ, Oza Tags: Clin Cancer Res Source Type: research

Local intracerebral immunomodulation using interleukin-expressing mesenchymal stem cells in glioblastoma.
CONCLUSION: Local MSC-based immunomodulation is able to efficiently alter the immunosuppressive microenvironment in glioblastoma. The long-lasting therapeutic effects warrant a rapid clinical translation of this concept and have led to planning of a phase I/II study of apceth-301 in recurrent glioblastoma. PMID: 31988196 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 27, 2020 Category: Cancer & Oncology Authors: Mohme M, Maire CL, Geumann U, Schliffke S, Dührsen L, Fita KD, Akyüz N, Binder M, Westphal M, Guenther C, Lamszus K, Hermann FG, Schmidt NO Tags: Clin Cancer Res Source Type: research

Association of anti-TNF with decreased survival in steroid refractory ipilimumab and anti-PD1 treated patients in the Dutch Melanoma Treatment Registry.
Conclusion Patients experiencing severe ICI toxicity have a prolonged overall survival. However, this survival advantage is abrogated when anti-TNF is administered for steroid-refractory toxicity. Further prospective studies are needed to assess the effect of different immunosuppressive regimens on checkpoint inhibitor efficacy. PMID: 31988197 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 27, 2020 Category: Cancer & Oncology Authors: Verheijden RJ, May AM, Blank CU, Aarts MJB, van den Berkmortel FWPJ, van den Eertwegh AJM, de Groot JWB, Boers-Sonderen MJ, van der Hoeven JJM, Hospers GA, Piersma D, van Rijn RS, Ten Tije A, van der Veldt AA, Vreugdenhil G, van Zeijl MCT, Wouters MWJM, H Tags: Clin Cancer Res Source Type: research

BRAF and DIS3 Mutations Associate with Adverse Outcome in a Long-term Follow-up of Patients with Multiple Myeloma.
CONCLUSION: Overall, these data highlight the importance of mutational screening to better understand newly diagnosed MM (NDMM) and may lead to patient specific mutation-driven treatment approaches. PMID: 31988198 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 27, 2020 Category: Cancer & Oncology Authors: Boyle EM, Ashby C, Tytarenko R, Deshpande S, Wang Y, Sawyer J, Tian E, Johnson S, Rutherford MW, Wardell CP, Bauer MA, Thanendrarajan S, Schinke C, Zangari M, van Rhee F, Wang H, Rosenthal A, Hoering A, Flynt E, Thakurta A, Dumontet C, Facon T, Cairns DA, Tags: Clin Cancer Res Source Type: research

Predicting Therapeutic Antibody Delivery into Human Head and Neck Cancers.
CONCLUSIONS: This study provides a clinically translatable platform to measure antibody delivery into solid tumors and yields valuable insight into clinically relevant antibody tumor penetration, with implications in the selection of patients amenable to antibody therapy and the design of more effective dosing strategies. PMID: 31980465 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 24, 2020 Category: Cancer & Oncology Authors: Lu G, Fakurnejad S, Martin BA, van den Berg NS, van Keulen S, Nishio N, Zhu AJ, Chirita SU, Zhou Q, Gao RW, Kong CS, Fischbein N, Penta M, Colevas AD, Rosenthal EL Tags: Clin Cancer Res Source Type: research