Pediatric PK/PD Phase I Trial of Pexidartinib in Relapsed and Refractory Leukemias and Solid Tumors Including Neurofibromatosis Type I related Plexiform Neurofibromas.
CONCLUSIONS: Pexidartinib in pediatric pts was well tolerated at all DL tested, achieved target inhibition and resulted in a weight based RPD2 dose. PMID: 32943455 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - September 17, 2020 Category: Cancer & Oncology Authors: Boal LH, Glod J, Spencer M, Kasai M, Derdak J, Dombi E, Ahlman M, Beury DW, Merchant M, Persenaire C, Liewehr DJ, Steinberg SM, Widemann BC, Kaplan RN Tags: Clin Cancer Res Source Type: research

Characterization of stromal tumor-infiltrating lymphocytes and genomic alterations in metastatic lobular breast cancer.
CONCLUSIONS: ILC metastases harbor genomic alterations that may potentially explain endocrine resistance in a large proportion of patients, and present genomic differences as compared to IDC metastases. PMID: 32943456 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - September 17, 2020 Category: Cancer & Oncology Authors: Richard F, Majjaj S, Venet D, Rothé F, Pingitore J, Boeckx B, Marchiò C, Clatot F, Bertucci F, Mariani O, Galant C, Van den Eynden GG, Salgado R, Biganzoli E, Lambrechts D, Vincent-Salomon A, Pruneri G, Larsimont DP, Sotiriou C, Desmedt C Tags: Clin Cancer Res Source Type: research

Phase 1B Study of Chemoprevention with Green Tea Polyphenon E and Erlotinib in Patients with Advanced Premalignant Lesions (APL) of the Head and Neck.
CONCLUSION: Treatment with PPE and erlotinib combination was well tolerated in patients with APLs of the head and neck, and showed a high rate of pathologic response with excellent CFS. This combination deserves further investigation for the chemoprevention and/or prevention of second primary tumors in early stage head and neck cancer. PMID: 32943457 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - September 17, 2020 Category: Cancer & Oncology Authors: Shin DM, Nannapaneni S, Patel MR, Shi Q, Liu Y, Chen Z, Chen A, El-Deiry MW, Beitler JJ, Steuer CE, Roser SM, Klein AM, Owonikoko TK, Ramalingam SS, Khuri FR, Chen ZG, Saba NF Tags: Clin Cancer Res Source Type: research

STAT3 antisense oligonucleotide remodels the suppressive tumor microenvironment to enhance immune activation in combination with anti-PD-L1.
CONCLUSIONS: STAT3 ASO treatment reverses a suppressive TME and promotes pro-inflammatory gene expression changes in patients' tumors and mouse models. Preclinical data provide evidence that ASO-mediated inhibition of STAT3 in the immune compartment is sufficient to remodel the TME and enhance the activity of checkpoint blockade without direct STAT3 inhibition in tumor cells. Collectively, these data provide rationale for testing this combination in the clinic. PMID: 32943458 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - September 17, 2020 Category: Cancer & Oncology Authors: Proia T, Singh M, Woessner R, Carnevalli LS, Bommakanti G, Magiera L, Srinivasan SS, Grosskurth SE, Collins M, Womack C, Griffin M, Ye M, Cantin S, Russell DL, Xie M, Hughes AM, Deng N, Mele DA, Fawell SE, Barry ST, Reimer C, Barrett JC, McCoon P Tags: Clin Cancer Res Source Type: research

Amphiregulin expression is a predictive biomarker for EGFR inhibition in metastatic colorectal cancer: combined analysis of three randomized trials.
CONCLUSIONS: High AREG mRNA expression is a favorable prognostic biomarker for mCRC which interacted significantly with efficacy of anti-EGFR treatment. PMID: 32943459 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - September 17, 2020 Category: Cancer & Oncology Authors: Stahler A, Stintzing S, Modest DP, Ricard I, Giessen-Jung C, Kapaun C, Ivanova B, Kaiser F, Fischer von Weikersthal L, Moosmann N, Schalhorn A, Stauch M, Kiani A, Held S, Decker T, Moehler M, Neumann J, Kirchner T, Jung A, Heinemann V Tags: Clin Cancer Res Source Type: research

Intratumoral Immunotherapy: from Trial Design to Clinical Practice.
Abstract Systemic immunotherapies such as immune checkpoint blockade targeted at PD(L)1 and CTLA4 have demonstrated their ability to provide durable tumor responses and long term overall survival benefits for some patients in several solid tumor types. However, a majority of patients remain resistant to these treatments and a significant proportion of them develop severe auto-immune and inflammatory adverse events. Pre-clinical studies have demonstrated that intratumoral injections of immunostimulatory products (oncolytics, pattern recognition receptor agonists,...) that are able to trigger type I interferon relea...
Source: Clinical Cancer Research - September 17, 2020 Category: Cancer & Oncology Authors: Champiat S, Tselikas L, Farhane S, Raoult T, Texier M, Lanoy E, Massard C, Robert C, Ammari S, De Baere T, Marabelle A Tags: Clin Cancer Res Source Type: research

Dual Blockade of c-MET and the Androgen Receptor in Metastatic Castration-Resistant Prostate Cancer: A Phase 1 Study of Concurrent Enzalutamide and Crizotinib.
CONCLUSIONS: Concurrent administration of enzalutamide and crizotinib resulted in a clinically significant 74% decrease in systemic crizotinib exposure. Further investigation of this combination in CRPC is not planned. Our results highlight the importance of evaluating pharmacokinetic interactions when evaluating novel combination strategies in CRPC. PMID: 32943461 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - September 17, 2020 Category: Cancer & Oncology Authors: Tripathi A, Supko JG, Gray KP, Melnick Z, Regan MM, Taplin ME, Choudhury AD, Pomerantz MM, Bellmunt J, Yu C, Sun Z, Srinivas S, Kantoff PW, Sweeney CJ, Harshman LC Tags: Clin Cancer Res Source Type: research

Palbociclib and trastuzumab in HER2-positive advanced breast cancer: Results from the phase II SOLTI-1303 PATRICIA trial.
CONCLUSION: Palbociclib in combination with trastuzumab is safe and exhibits promising survival outcomes in trastuzumab pre-treated ER-positive/HER2-positive advanced breast cancer with a PAM50 luminal A or B subtype. The enrollment was stopped prematurely and a new randomized cohort was opened in this population. PMID: 32938620 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - September 16, 2020 Category: Cancer & Oncology Authors: Ciruelos EM, Villagrasa P, Pascual T, Oliveira M, Pernas S, Paré L, Escrivá-de-Romaní S, Manso L, Adamo B, Martínez de Dueñas E, Cortés J, Vázquez S, Perelló A, Garau I, Melé M, Martínez Jañez N, Montaño A, Bermejo B, Morales S, Echarri MJ, Ve Tags: Clin Cancer Res Source Type: research

Serum IL-6 as a prognostic biomarker and IL-6R as a therapeutic target in biliary tract cancers.
CONCLUSIONS: Serum IL-6 and YKL-40 are potential new prognostic biomarkers in BTC. IL-6 provides independent prognostic information and may be superior to CA19-9 in certain contexts. Moreover, anti-IL-6R should be considered as a new treatment option to sustain gemcitabine response in BTC patients. PMID: 32933994 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - September 15, 2020 Category: Cancer & Oncology Authors: Hogdall DTS, O'Rourke CJ, Dehlendorff C, Larsen FO, Jensen LH, Johansen AZ, Dang H, Factor VM, Grunnet M, Mau-Sørensen M, Oliveira DVNP, Linnemann D, Boisen MK, Wang XW, Johansen JS, Andersen JB Tags: Clin Cancer Res Source Type: research

Concomitant Proton Pump Inhibitor Use and Survival in Urothelial Carcinoma Treated with Atezolizumab.
Abstract PURPOSE: Emerging evidence indicates that gut microbiota dysbiosis can reduce the effectiveness of immune checkpoint inhibitors (ICI). Proton pump inhibitors (PPI) are known to induce gut microbiota changes. However, little is known on the effects of PPIs on outcomes with ICI therapy, and it has not been explored in urothelial cancer treatment. EXPERIMENTAL DESIGN: Individual-participant data from the advanced urothelial cancer trials, IMvigor210 (single-arm atezolizumab trial, n = 429) and IMvigor211 (phase III randomized trial of atezolizumab vs. chemotherapy, n = 931) were pooled in a Cox proporti...
Source: Clinical Cancer Research - September 15, 2020 Category: Cancer & Oncology Authors: Hopkins AM, Kichenadasse G, Karapetis CS, Rowland A, Sorich MJ Tags: Clin Cancer Res Source Type: research

TSPO-targeted PET and Optical Probes for the Detection and Localization of Pre-Malignant and Malignant Pancreatic Lesions.
CONCLUSIONS: We anticipate that combined TSPO PET/IGS represents a translational approach for precision pancreatic cancer care through discrimination of high-risk indeterminate lesions and actionable surgery. PMID: 32933996 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - September 15, 2020 Category: Cancer & Oncology Authors: Cohen AS, Li J, Hight MR, McKinley ET, Fu A, Payne AC, Liu Y, Zhang D, Xie Q, Bai M, Ayers GD, Tantawy MN, Smith JA, Revetta F, Washington MK, Shi C, Merchant NB, Manning HC Tags: Clin Cancer Res Source Type: research

Chloroquine sensitizes GNAQ/11-mutated melanoma to MEK1/2 inhibition.
CONCLUSIONS: These results suggest that YAP, MEK1/2, and lysosome function are necessary and critical targets for the therapy of GNAQ/11-driven melanoma, and identify trametinib plus hydroxychloroquine as a potential treatment strategy for metastatic uveal melanoma. PMID: 32933997 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - September 15, 2020 Category: Cancer & Oncology Authors: Truong A, Yoo JH, Scherzer M, Sanchez JMS, Dale KJ, Kinsey CG, Richards JR, Shin D, Ghazi P, Onken MD, Blumer KJ, Odelberg SJ, McMahon M Tags: Clin Cancer Res Source Type: research

Radiotheranostic Agent 64Cu-cyclam-RAFT-c(-RGDfK-)4 for Management of Peritoneal Metastasis in Ovarian Cancer.
CONCLUSIONS: Collectively, these results demonstrate the all-in-one potential of 64Cu-RaftRGD for imaging-guided radiotherapy of OCPM by targeting both tumoral neovessels and cancerous cells. Based on the ITD finding, we propose that pairing αVβ3- and hypoxia-targeted radiotherapies could improve therapeutic efficacy by overcoming the heterogeneity of ITD encountered with single-agent treatments. PMID: 32933998 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - September 15, 2020 Category: Cancer & Oncology Authors: Jin ZH, Tsuji AB, Degardin M, Sugyo A, Obara S, Wakizaka H, Nagatsu K, Hu K, Zhang MR, Dumy P, Boturyn D, Higashi T Tags: Clin Cancer Res Source Type: research

Selected Articles from This Issue.
Authors: PMID: 32934028 [PubMed - in process] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - September 15, 2020 Category: Cancer & Oncology Tags: Clin Cancer Res Source Type: research

Correction: Safety, Efficacy, and Biomarker Analysis of Toripalimab in Previously Treated Advanced Melanoma: Results of the POLARIS-01 Multicenter Phase II Trial.
PMID: 32934029 [PubMed - in process] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - September 15, 2020 Category: Cancer & Oncology Authors: Tang B, Chi Z, Chen Y, Liu X, Wu D, Chen J, Song X, Wang W, Dong L, Song H, Wu H, Feng H, Yao S, Qin S, Zhang X, Guo J Tags: Clin Cancer Res Source Type: research

Correction: Alterations in the Transcriptional Programs of Myeloma Cells and the Microenvironment during Extramedullary Progression Affect Proliferation and Immune Evasion.
PMID: 32934030 [PubMed - in process] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - September 15, 2020 Category: Cancer & Oncology Authors: Ryu D, Kim SJ, Hong Y, Jo A, Kim N, Kim HJ, Lee HO, Kim K, Park WY Tags: Clin Cancer Res Source Type: research

Correction: Paclitaxel Sensitivity of Ovarian Cancer Can be Enhanced by Knocking Down Pairs of Kinases that Regulate MAP4 Phosphorylation and Microtubule Stability.
PMID: 32934031 [PubMed - in process] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - September 15, 2020 Category: Cancer & Oncology Authors: Yang H, Mao W, Rodriguez-Aguayo C, Mangala LS, Bartholomeusz G, Iles LR, Jennings NB, Ahmed AA, Sood AK, Lopez-Berestein G, Lu Z, Bast RC Tags: Clin Cancer Res Source Type: research

Correction: Influencing the Tumor Microenvironment: A Phase II Study of Copper Depletion Using Tetrathiomolybdate in Patients with Breast Cancer at High Risk for Recurrence and in Preclinical Models of Lung Metastases.
PMID: 32934032 [PubMed - in process] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - September 15, 2020 Category: Cancer & Oncology Authors: Chan N, Willis A, Kornhauser N, Ward MM, Lee SB, Nackos E, Seo BR, Chuang E, Cigler T, Moore A, Donovan D, Cobham MV, Fitzpatrick V, Schneider S, Wiener A, Guillaume-Abraham J, Aljom E, Zelkowitz R, Warren JD, Lane ME, Fischbach C, Mittal V, Vahdat L Tags: Clin Cancer Res Source Type: research

Editor's Note: The Pivotal Role of Integrin β1 in Metastasis of Head and Neck Squamous Cell Carcinoma.
Editor's Note: The Pivotal Role of Integrin β1 in Metastasis of Head and Neck Squamous Cell Carcinoma. Clin Cancer Res. 2020 Sep 15;26(18):5052 Authors: Wang D, Müller S, Ruhul Amin ARM, Huang D, Su L, Hu Z, Rahman MA, Nannapaneni S, Koenig L, Chen Z, Tighiouart M, Shin DM, Chen ZG PMID: 32934033 [PubMed - in process] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - September 15, 2020 Category: Cancer & Oncology Authors: Wang D, Müller S, Ruhul Amin ARM, Huang D, Su L, Hu Z, Rahman MA, Nannapaneni S, Koenig L, Chen Z, Tighiouart M, Shin DM, Chen ZG Tags: Clin Cancer Res Source Type: research

Iron induces cell death and strengthens the efficacy of anti-androgen therapy in prostate cancer models.
CONCLUSIONS: Our models allow us to dissect the direct iron effect on cancer cells. We demonstrate the proof of principle that iron toxicity inhibits PCa cell proliferation, proposing a novel tool to strengthen anti-androgen treatment efficacy. PMID: 32928793 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - September 14, 2020 Category: Cancer & Oncology Authors: Bordini J, Morisi F, Elia AR, Santambrogio P, Pagani A, Cucchiara V, Ghia P, Bellone M, Briganti A, Camaschella C, Campanella A Tags: Clin Cancer Res Source Type: research

Steroid sulfatase stimulates intracrine androgen synthesis and is a therapeutic target for advanced prostate cancer.
CONCLUSIONS: These studies suggest that STS drives intracrine androgen synthesis and prostate cancer proliferation. Targeting STS represents a therapeutic strategy to treat CRPC and improve second generation anti-androgen therapy. PMID: 32928794 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - September 14, 2020 Category: Cancer & Oncology Authors: Gao AC, Armstrong CM, Liu C, Liu L, Yang JC, Lou W, Zhao R, Ning S, Lombard AP, Zhao J, D'Abronzo LS, Evans CP, Li PK Tags: Clin Cancer Res Source Type: research

Immunomodulation in pomalidomide, dexamethasone, and daratumumab -treated relapsed/refractory multiple myeloma patients.
CONCLUSIONS: These data support a potential mechanism for enhanced immune-mediated cytotoxicity in which DARA-mediated NK cell diminution is partially offset by POM effects on the remaining NK cell pool. Further, DARA antimyeloma activity and elimination of CD38+ T cells (regulatory/activated) provides a rationale for therapeutic combination with direct tumoricidal activity and immunomodulation of POM-directed T cell enhancements. These data highlight enhancements in immune subpopulations for the combination of DARA with POM and potentially with next generation cereblon-targeting agents. PMID: 32928795 [PubMed - as su...
Source: Clinical Cancer Research - September 14, 2020 Category: Cancer & Oncology Authors: Pierceall WE, Amatangelo MD, Bahlis NJ, Siegel DS, Rahman A, Van Oekelen O, Neri P, Young M, Chung W, Serbina N, Parekh S, Agarwal A, Thakurta A Tags: Clin Cancer Res Source Type: research

Flumatinib versus Imatinib for Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia: A Phase 3, Randomized, Open-label, Multi-center FESTnd Study.
In this study, 394 patients were randomized 1:1 to flumatinib 600 mg once daily (n=196) or imatinib 400 mg once daily (n=198). RESULTS: The rate of major molecular response (MMR) at 6 months (primary end point) was significantly higher with flumatinib than with imatinib (33.7% vs 18.3%, P=0.0006), as was the rate of MMR at 12 months (52.6% vs 39.6%, P=0.0102). At 3 months, the rate of early molecular response (EMR) was significantly higher in patients receiving flumatinib than in those receiving imatinib (82.1% vs 53.3%, P
Source: Clinical Cancer Research - September 14, 2020 Category: Cancer & Oncology Authors: Zhang L, Meng L, Liu B, Zhang Y, Zhu H, Cui J, Sun A, Hu Y, Jin J, Jiang H, Zhang X, Li Y, Liu L, Zhang W, Liu X, Gu J, Qiao J, Ouyang G, Liu X, Luo J, Jiang M, Xie X, Li J, Zhao C, Zhang M, Yang T, Wang J Tags: Clin Cancer Res Source Type: research

The capacity of the ovarian cancer tumor microenvironment to integrate inflammation signaling conveys a shorter disease-free interval.
CONCLUSIONS: Multi-omic profiling of ovarian tumor samples pre- and post-NACT provides unique insight into chemo-induced changes to the tumor microenvironment. We identified a novel IL-6/IER3 signaling axis that may drive chemo-resistance and disease recurrence. PMID: 32928797 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - September 14, 2020 Category: Cancer & Oncology Authors: Jordan K, Sikora MJ, Slansky JE, Minic A, Richer JK, Moroney MR, Hu J, Wolsky RJ, Watson ZL, Yamamoto TM, Costello JC, Clauset A, Behbakht K, Kumar TR, Bitler BG Tags: Clin Cancer Res Source Type: research

Potent activity of an anti-ICAM1 antibody-drug conjugate against multiple myelom.
CONCLUSION: We propose that anti-ICAM1 antibody-drug conjugate should be further studied for toxicity, and if safe, tested for clinical efficacy in patients with relapsed or refractory multiple myeloma. PMID: 32917735 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - September 11, 2020 Category: Cancer & Oncology Authors: Sherbenou DW, Su Y, Behrens CR, Aftab BT, Perez de Acha O, Murnane M, Bearrows SC, Hann B, Wolf JL, Martin TG, Liu B Tags: Clin Cancer Res Source Type: research

Multiplex immunofluorescence in formalin-fixed paraffin-embedded tumor tissue to identify single cell-level PI3K pathway activation.
CONCLUSION: Our novel pathway-focused approach to quantifying single cell-level immunofluorescence in FFPE tissue identifies prostate tumors with PI3K pathway activation that are more aggressive and may respond to pathway inhibitors. PMID: 32913135 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - September 10, 2020 Category: Cancer & Oncology Authors: Stopsack KH, Huang Y, Tyekucheva S, Gerke TA, Bango C, Elfandy H, Bowden M, Penney KL, Roberts TM, Parmigiani G, Kantoff PW, Mucci LA, Loda M Tags: Clin Cancer Res Source Type: research

Gene networks constructed through simulated treatment learning can predict proteasome inhibitor benefit in Multiple Myeloma.
CONCLUSIONS: STLsig can identify gene signatures that could aid in treatment decisions for MM patients and provide insight into the biological mechanism behind treatment benefit. PMID: 32913136 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - September 10, 2020 Category: Cancer & Oncology Authors: Ubels J, Sonneveld P, van Vliet MH, de Ridder J Tags: Clin Cancer Res Source Type: research

Sebaceous carcinoma epidemiology and genetics: Emerging concepts and clinical implications for screening, prevention, and treatment.
Abstract Sebaceous carcinoma is an aggressive skin cancer with a 5-year overall survival rate of 78% for localized/regional disease and 50% for metastatic disease. The incidence of this cancer has been increasing in the United States for several decades, but the underlying reasons for this increase are unclear. In this article, we review the epidemiology and genetics of sebaceous carcinoma, including recent population data and tumor genomic analyses that provide new insights into underlying tumor biology. We further discuss emerging evidence of a possible viral etiology for this cancer. Lastly, we review the clini...
Source: Clinical Cancer Research - September 9, 2020 Category: Cancer & Oncology Authors: Sargen MR, Starrett GJ, Engels EA, Cahoon EK, Tucker MA, Goldstein AM Tags: Clin Cancer Res Source Type: research

Multimodal CEA-targeted image-guided colorectal cancer surgery using 111In-labeled SGM-101.
ema M Abstract PURPOSE: Intraoperative image guidance may aid in clinical decision making during surgical treatment of colorectal cancer. We developed the dual-labeled CEA-targeting tracer [111In]In-DTPA-SGM-101 for pre- and intraoperative imaging of colorectal cancer. Subsequently we investigated the tracer in preclinical biodistribution and multimodal image-guided surgery studies, and assessed the clinical feasibility on patient derived colorectal cancer samples, paving the way for rapid clinical translation. EXPERIMENTAL DESIGN: SGM-101 was conjugated with p-isothiocyanatobenzyl (ITC)-diethylenetriaminepen...
Source: Clinical Cancer Research - September 8, 2020 Category: Cancer & Oncology Authors: de Gooyer JM, Elekonawo FMK, Bos DL, van der Post RS, Pèlegrin A, Framery B, Cailler F, Vahrmeijer AL, de Wilt JHW, Rijpkema M Tags: Clin Cancer Res Source Type: research

Epithelial to mesenchymal transition is a cause of both intrinsic and acquired resistance to KRAS G12C inhibitor in KRAS G12C mutant non-small cell lung cancer.
CONCLUSIONS: Our findings suggest that EMT is a cause of both intrinsic and acquired resistance by activating the PI3K pathway in the presence of KRAS G12C inhibitor. PMID: 32900796 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - September 8, 2020 Category: Cancer & Oncology Authors: Adachi Y, Ito K, Hayashi Y, Kimura R, Tan TZ, Yamaguchi R, Ebi H Tags: Clin Cancer Res Source Type: research

CSPG4-specific CAR.CIK lymphocytes as a novel therapy for the treatment of multiple soft tissue sarcoma histotypes.
CONCLUSIONS: This study has shown that CSPG4-specific CAR-redirected CIK effectively target multiple STS histotypes in vitro and in immunodeficient mice. These results provide a strong rationale to translate the novel strategy we have developed in to a clinical setting. PMID: 32900797 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - September 8, 2020 Category: Cancer & Oncology Authors: Leuci V, Donini C, Grignani G, Rotolo R, Mesiano G, Fiorino E, Gammaitoni L, D'Ambrosio L, Merlini A, Landoni E, Medico E, Capellero S, Giraudo L, Cattaneo G, Iaia I, Pignochino Y, Basiricò M, Vigna E, Pisacane A, Fagioli F, Ferrone S, Aglietta M, Gianpi Tags: Clin Cancer Res Source Type: research

AsiDNA is a radiosensitizer with no added toxicity in medulloblastoma pediatric models.
CONCLUSIONS: Our results suggest that AsiDNA is an attractive candidate to improve radiation therapy in MB, with no indication of additional toxicity in developing brain tissues. PMID: 32900798 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - September 8, 2020 Category: Cancer & Oncology Authors: Ferreira S, Foray C, Gatto A, Larcher M, Heinrich S, Lupu M, Mispelter J, Boussin FD, Pouponnot C, Dutreix M Tags: Clin Cancer Res Source Type: research

Effects of acute and chronic graft-versus-myelodysplastic syndrome on long-term outcomes following allogeneic hematopoietic cell transplantation.
CONCLUSIONS: These data demonstrated a survival benefit of the graft-versus-MDS effect is present only in high-risk MDS patients with limited chronic GVHD. PMID: 32895232 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - September 6, 2020 Category: Cancer & Oncology Authors: Konuma T, Ishiyama K, Igarashi A, Uchida N, Ozawa Y, Fukuda T, Ueda Y, Matsuoka KI, Mori T, Katayama Y, Onizuka M, Ichinohe T, Atsuta Y Tags: Clin Cancer Res Source Type: research

Statins as anti-cancer agents in the era of precision medicine.
Abstract Statins are widely prescribed cholesterol-lowering drugs that inhibit HMG-CoA reductase (HMGCR), the rate-limiting enzyme of the mevalonate (MVA) metabolic pathway. Multiple lines of evidence indicate that certain cancers depend on the MVA pathway for growth and survival, and therefore are vulnerable to statin therapy. However, these immediately available, well tolerated and inexpensive drugs have yet to be successfully repurposed and integrated into cancer patient care. In this Review, we highlight recent advances and outline important considerations for advancing statins to clinical trials in oncology. ...
Source: Clinical Cancer Research - September 4, 2020 Category: Cancer & Oncology Authors: Longo J, van Leeuwen JE, Elbaz M, Branchard E, Penn LZ Tags: Clin Cancer Res Source Type: research

Phase Ib Study of Ribociclib Plus Fulvestrant and Ribociclib Plus Fulvestrant Plus PI3K-Inhibitor (Alpelisib or Buparlisib) for HR+ Advanced Breast Cancer.
CONCLUSIONS: Ribociclib plus fulvestrant demonstrated safety in the treatment of patients with HR+, HER2- ABC. Triple combinations with alpelisib or buparlisib plus fulvestrant are not recommended for phase II investigation. NCT02088684. PMID: 32887722 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - September 4, 2020 Category: Cancer & Oncology Authors: Tolaney SM, Im YH, Calvo E, Lu YS, Hamilton EP, Forero-Torres A, Bachelot T, Maur M, Fasolo A, Tiedt R, Nardi L, Stammberger U, Abdelhady AM, Ruan S, Lee SC Tags: Clin Cancer Res Source Type: research

Circulating T-cell immunosenescence in advanced non-small cell lung cancer patients treated with single agent PD-1/PD-L1 inhibitors or platinum-based chemotherapy.
CONCLUSIONS: Circulating T-cell immunosenescence is observed in up to 28% of aNSCLC patients and correlates with lack of benefit from ICI but not from PCT. PMID: 32887723 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - September 4, 2020 Category: Cancer & Oncology Authors: Ferrara R, Naigeon M, Auclin E, Duchemann B, Cassard L, Jouniaux JM, Boselli L, Grivel J, Desnoyer A, Mezquita L, Texier M, Caramella C, Hendriks LEL, Planchard D, Remon J, Sangaletti S, Proto C, Garassino MC, Soria JC, Marabelle A, Voisin AL, Farhane S, Tags: Clin Cancer Res Source Type: research

PD1 blockade enhances ICAM1-directed CAR T therapeutic efficacy in advanced thyroid cancer.
CONCLUSIONS: Targeting two IFNg-inducible, tumor-associated antigens - ICAM1 and PD-L1 - in a complementary manner might be an effective treatment strategy to control advanced thyroid cancers in vivo. PMID: 32887724 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - September 4, 2020 Category: Cancer & Oncology Authors: Gray KD, McCloskey JE, Vedvyas Y, Kalloo OR, El Eshaky S, Yang Y, Shevlin E, Zaman M, Ullmann TM, Liang H, Stefanova D, Christos PJ, Scognamiglio T, Tassler AB, Zarnegar R, Fahey TJ, Jin MM, Min IM Tags: Clin Cancer Res Source Type: research

Safety and Clinical Activity of MEDI1873, a Novel GITR Agonist, in Advanced Solid Tumors.
CONCLUSIONS: MEDI1873 showed acceptable safety up to 500 mg IV Q2W with pharmacodynamic activity, and prolonged SD in some patients. However, further development is not planned due to lack of demonstrated tumor response. PMID: 32887725 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - September 4, 2020 Category: Cancer & Oncology Authors: Balmanoukian A, Infante JR, Aljumaily R, Naing A, Chintakuntlawar AV, Rizvi NA, Ross HJ, Gordon M, Mallinder PR, Elgeioushi N, González-García I, Standifer N, Cann J, Durham N, Rahimian S, Kumar R, Denlinger CS Tags: Clin Cancer Res Source Type: research

Targeting isocitrate dehydrogenase mutations in cancer: emerging evidence and diverging strategies.
Abstract Isocitrate dehydrogenase active-site mutations cause a neomorphic enzyme activity that results in the formation of supraphysiological concentrations of D-2-hydroxyglutarate (D-2HG). D-2HG is thought to be an oncometabolite that drives the formation of cancers in a variety of tissue types by altering the epigenetic state of progenitor cells by inhibiting enzymes involved in histone and DNA demethylation. This model has led to the development of pharmacological inhibitors of mutant IDH activity for anti-cancer therapy, which are now being tested in several clinical trials. Emerging evidence in preclinical g...
Source: Clinical Cancer Research - September 3, 2020 Category: Cancer & Oncology Authors: Waitkus MS, Yan H Tags: Clin Cancer Res Source Type: research

Comprehensive genomic profiling of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs).
Abstract PURPOSE: GEP-NENs are rare malignancies with increasing incidence. Their molecular characteristics are still undefined. We explored the underlying biology of GEP-NENs and the differences between gastrointestinal (GI) and pancreatic (PNET), high grade (HG) and low grade (LG) tumors. EXPERIMENTAL DESIGN: GEP-NENs were analyzed using next-generation sequencing (NGS; MiSeq on 47 genes, NextSeq on 592 genes), immunohistochemistry, and in-situ hybridization. Tumor mutational burden (TMB) was calculated based on somatic nonsynonymous missense mutations, and microsatellite instability (MSI) was evaluated by ...
Source: Clinical Cancer Research - September 3, 2020 Category: Cancer & Oncology Authors: Puccini A, Poorman K, Salem ME, Soldato D, Seeber A, Goldberg RM, Shields AF, Xiu J, Battaglin F, Berger MD, Tokunaga R, Naseem M, Barzi A, Iqbal S, Zhang W, Soni S, Hwang JJ, Philip PA, Sciallero S, Korn WM, Marshall JL, Lenz HJ Tags: Clin Cancer Res Source Type: research

Phase 1 and Biomarker Study of the Wnt Pathway Modulator DKN-01 in Combination with Gemcitabine/Cisplatin in Advanced Biliary Tract Cancer.
CONCLUSIONS: DKN-01 300mg was well tolerated in this combination but did not appear to have additional activity beyond historically reported efficacy with gemcitabine/cisplatin alone. Exploratory pharmacokinetic and biomarker data indicate potential antiangiogenic and immunomodulatory activity of DKN-01/chemotherapy and the need for increased dose/intensity. A study with DKN-01 600mg in combination with a PD-1 inhibitor in BTC is ongoing. PMID: 32878766 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - September 2, 2020 Category: Cancer & Oncology Authors: Goyal L, Sirard C, Schrag M, Kagey MH, Eads JR, Stein S, El-Khoueiry AB, Manji GA, Abrams TA, Khorana AA, Miksad R, Mahalingam D, Zhu AX, Duda DG Tags: Clin Cancer Res Source Type: research

Copy number alteration burden differentially impacts immune profiles and molecular features of hepatocellular carcinoma.
CONCLUSIONS: HCCs with high chromosomal instability exhibit features of immune exclusion, whereas tumors displaying low burdens of broad CNAs present an immune active profile. These CNA scores can be tested to predict response to immunotherapies. PMID: 32873569 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - September 1, 2020 Category: Cancer & Oncology Authors: Bassaganyas L, Pinyol R, Esteban-Fabró R, Torrens L, Torrecilla S, Willoughby CE, Franch-Expósito S, Vila-Casadesús M, Salaverria I, Montal R, Mazzaferro V, Camps J, Sia D, Llovet JM Tags: Clin Cancer Res Source Type: research

Long-term outcomes of oral vinorelbine in advanced, progressive desmoid fibromatosis and influence of CTNNB1 mutational status.
CONCLUSION: Oral vinorelbine is an effective, affordable and well tolerated regimen in patients with advanced, progressive DF. Prolonged activity was observed in patients with tumors harboring CTNNB1 p.S45F or p.S45P mutations. PMID: 32873570 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - September 1, 2020 Category: Cancer & Oncology Authors: Mir O, Honoré C, Chamseddine AN, Dômont J, Dumont SN, Cavalcanti A, Faron M, Rimareix F, Haddag-Miliani L, Le Péchoux C, Levy A, Court C, Briand S, Fadel E, Mercier O, Bayle A, Brunet A, Ngo C, Rouleau E, Adam J, Le Cesne A Tags: Clin Cancer Res Source Type: research

CXCR3 and Cognate Ligands Are Associated with Immune Cell Alteration and Aggressiveness of Pancreatic Ductal Adenocarcinoma.
CONCLUSION: CXCR3-ligands are overexpressed in PDAC and are associated with poor survival likely related to alterations in tumor immune infiltrate/activity. PMID: 32873571 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - September 1, 2020 Category: Cancer & Oncology Authors: Batra SK, Cannon A, Thompson CM, Maurer C, Atri P, Bhatia R, West S, Ghersi D, Olive KP, Kumar S Tags: Clin Cancer Res Source Type: research

Efficacy and Safety of Nivolumab Plus Ipilimumab versus Sunitinib in First-Line Treatment of Patients with Advanced Sarcomatoid Renal Cell Carcinoma.
CONCLUSIONS: NIVO+IPI showed unprecedented long-term survival, response and complete response benefits versus SUN in previously untreated patients with sRCC and intermediate/poor-risk disease, supporting the use of first-line NIVO+IPI for this population. PMID: 32873572 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - September 1, 2020 Category: Cancer & Oncology Authors: Tannir NM, Signoretti S, Choueiri TK, McDermott DF, Motzer RJ, Flaifel A, Pignon JC, Ficial M, Arén Frontera O, George S, Donskov F, Harrison MR, Powles T, Barthélémy P, Tykodi SS, Kocsis J, Ravaud A, Rodriguez-Cid JR, Pal SK, Murad AM, Ishii Y, Saggi Tags: Clin Cancer Res Source Type: research

Targeted Natural Killer Cell-Based Adoptive Immunotherapy for the Treatment of Patients with NSCLC after Radiochemotherapy: A Randomized Phase II Clinical Trial.
CONCLUSIONS: Ex vivo TKD/IL2-activated, autologous NK cells are well tolerated and deliver positive clinical responses in patients with advanced NSCLC after RCT. PMID: 32873573 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - September 1, 2020 Category: Cancer & Oncology Authors: Multhoff G, Seier S, Stangl S, Sievert W, Shevtsov M, Werner C, Pockley AG, Blankenstein C, Hildebrandt M, Offner R, Ahrens N, Kokowski K, Hautmann M, Rödel C, Fietkau R, Lubgan D, Huber R, Hautmann H, Duell T, Molls M, Specht H, Haller B, Devecka M, Sau Tags: Clin Cancer Res Source Type: research

Selected Articles from This Issue.
Authors: PMID: 32873694 [PubMed - in process] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - September 1, 2020 Category: Cancer & Oncology Tags: Clin Cancer Res Source Type: research

Circulating tumor DNA genomics reveals potential mechanisms of resistance to BRAF-targeted therapies in BRAF-mutant metastatic non-small cell lung cancer patients.
Conclusions: ctDNA sequencing is clinically relevant for the detection of BRAF-activating mutations and the identification of alterations potentially related to resistance to BRAF-TT in BRAF-mutant NSCLC. PMID: 32859654 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - August 28, 2020 Category: Cancer & Oncology Authors: Ortiz-Cuaran S, Mezquita L, Swalduz A, Aldea M, Mazieres J, Leonce C, Jovelet C, Pradines A, Avrillon V, Chumbi Flores WR, Lacroix L, Loriot Y, Westeel V, Ngo-Camus M, Tissot C, Raynaud C, Gervais R, Brain E, Monnet I, Giroux Leprieur E, Caramella C, Mahi Tags: Clin Cancer Res Source Type: research

The Long and Winding Road for Breast Cancer Biomarkers to Reach Clinical Utility.
Abstract Tumor data from the ABCGS5 trial of chemotherapy versus endocrine therapy for premenopausal ER+ breast cancer supports molecular subtyping by Ki-67 immunochemistry as a prognostic marker. But while this tissue was handled uniformly, Ki67 testing overall is unstandardized, complicating clinical utility. Increasing potential biomarkers herald more challenges in biomarker validation. PMID: 32859655 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - August 28, 2020 Category: Cancer & Oncology Authors: Hunter NB, Kilgore MR, Davidson NE Tags: Clin Cancer Res Source Type: research

TRAIL and cancer immunotherapy: Take a walk on the short side.
Abstract Recent work shows that TRAILshort, a membrane-bound short form of TRAIL, is expressed by human cancer cells and protects them from TRAIL-induced cell death. A monoclonal antibody that selectively targets TRAILshort enhances cancer susceptibility to TRAIL and increases the efficacy of autologous CD8+T cells in ex vivo primary tumours. PMID: 32847932 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - August 26, 2020 Category: Cancer & Oncology Authors: De Miguel D, Pardo J Tags: Clin Cancer Res Source Type: research