Modified RANO (mRANO), iRANO, and standard RANO response to convection-enhanced delivery of IL4R-targeted immunotoxin MDNA55 in recurrent glioblastoma
Clin Cancer Res. 2021 Apr 16:clincanres.0446.2021. doi: 10.1158/1078-0432.CCR-21-0446. Online ahead of print.ABSTRACTPURPOSE: The current study compared the modified radiographic response assessment in neuro-oncology (mRANO), immunotherapy RANO (iRANO), and standard RANO criteria as well as quantified the association between progression-free (PFS) and overall survival (OS) in an immunotherapy trial in recurrent glioblastoma (rGBM).EXPERIMENTAL DESIGN: 47 patients with rGBM were enrolled in a prospective phase II convection-enhanced delivery of an IL4R-targeted immunotoxin (MDNA55-05, NCT02858895). Bidirectional tumor measu...
Source: Clinical Cancer Research - April 17, 2021 Category: Cancer & Oncology Authors: Benjamin M Ellingson John H Sampson Achal Singh Achrol Manish K Aghi Krystof Krystof Bankiewicz Chencai Wang Martin Bexon Steven Brem Andrew J Brenner Sajeel Chowdhary John R Floyd Seunggu Jude Han Santosh Kesari Dina Randazzo Michael A Vogelbaum Frank D Source Type: research

Safety, anti-tumor activity, and biomarker analysis in a phase 1 trial of the once-daily Wee1 inhibitor adavosertib (AZD1775) in patients with advanced solid tumors
CONCLUSIONS: We determined the once-daily adavosertib RPh2D and observed activity in patients with ovarian or endometrial carcinoma, including 2 with baseline CCNE1 mRNA overexpression. Future studies will determine whether CCNE1 overexpression is a predictive biomarker for adavosertib.PMID:33863809 | DOI:10.1158/1078-0432.CCR-21-0329 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 17, 2021 Category: Cancer & Oncology Authors: Naoko Takebe Abdul Rafeh Naqash Geraldine O'Sullivan Coyne Shivaani Kummar Khanh T Do Ashley Bruns Lamin Juwara Jennifer Zlott Lawrence Rubinstein Richard L Piekarz Elad Sharon Howard Streicher Arjun Mittra Sarah B Miller Jiuping Ji Deborah F Wilsker Robe Source Type: research

Modified RANO (mRANO), iRANO, and standard RANO response to convection-enhanced delivery of IL4R-targeted immunotoxin MDNA55 in recurrent glioblastoma
Clin Cancer Res. 2021 Apr 16:clincanres.0446.2021. doi: 10.1158/1078-0432.CCR-21-0446. Online ahead of print.ABSTRACTPURPOSE: The current study compared the modified radiographic response assessment in neuro-oncology (mRANO), immunotherapy RANO (iRANO), and standard RANO criteria as well as quantified the association between progression-free (PFS) and overall survival (OS) in an immunotherapy trial in recurrent glioblastoma (rGBM).EXPERIMENTAL DESIGN: 47 patients with rGBM were enrolled in a prospective phase II convection-enhanced delivery of an IL4R-targeted immunotoxin (MDNA55-05, NCT02858895). Bidirectional tumor measu...
Source: Clinical Cancer Research - April 17, 2021 Category: Cancer & Oncology Authors: Benjamin M Ellingson John H Sampson Achal Singh Achrol Manish K Aghi Krystof Krystof Bankiewicz Chencai Wang Martin Bexon Steven Brem Andrew J Brenner Sajeel Chowdhary John R Floyd Seunggu Jude Han Santosh Kesari Dina Randazzo Michael A Vogelbaum Frank D Source Type: research

Safety, anti-tumor activity, and biomarker analysis in a phase 1 trial of the once-daily Wee1 inhibitor adavosertib (AZD1775) in patients with advanced solid tumors
CONCLUSIONS: We determined the once-daily adavosertib RPh2D and observed activity in patients with ovarian or endometrial carcinoma, including 2 with baseline CCNE1 mRNA overexpression. Future studies will determine whether CCNE1 overexpression is a predictive biomarker for adavosertib.PMID:33863809 | DOI:10.1158/1078-0432.CCR-21-0329 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 17, 2021 Category: Cancer & Oncology Authors: Naoko Takebe Abdul Rafeh Naqash Geraldine O'Sullivan Coyne Shivaani Kummar Khanh T Do Ashley Bruns Lamin Juwara Jennifer Zlott Lawrence Rubinstein Richard L Piekarz Elad Sharon Howard Streicher Arjun Mittra Sarah B Miller Jiuping Ji Deborah F Wilsker Robe Source Type: research

Development and validation of a novel nomogram for individualized prediction of survival in cancer of unknown primary (CUP)
CONCLUSIONS: Our user-friendly CUP nomogram integrating commonly available baseline factors provides robust personalized prognostication which can aid clinical decision making and selection/stratification for clinical trials.PMID:33858857 | DOI:10.1158/1078-0432.CCR-20-4117 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 16, 2021 Category: Cancer & Oncology Authors: Kanwal Raghav Hyunsoo Hwang Alexandre A J ácome Eric Bhang Anneleis Willett Ryan W Huey Nishat P Dhillon Jignesh Modha Brandon G Smaglo Aurelio Matamoros Jeannelyn Santiano Estrella Justin Jao Michael J Overman Xuemei Wang F Anthony Greco Jonathan M Lore Source Type: research

CAR T cells Targeting Human Immunoglobulin Light Chains Eradicate Mature B Cell Malignancies While Sparing a Subset of Normal B Cells
CONCLUSIONS: Adoptive transfer of CAR.λ and CAR.κ-T cells represents a useful and alternative modality to CAR.CD19-T cells in treating mature B-cell malignancies with minimal impact on humoral immunity.PMID:33858858 | DOI:10.1158/1078-0432.CCR-20-2754 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 16, 2021 Category: Cancer & Oncology Authors: Raghuveer Ranganathan Peishun Shou Sarah Ahn Chuang Sun John West Barbara Savoldo Gianpietro Dotti Source Type: research

Molecular Subtypes of Pancreatic Cancer: A Proteomics Approach
Clin Cancer Res. 2021 Apr 14:clincanres.0640.2021. doi: 10.1158/1078-0432.CCR-21-0640. Online ahead of print.ABSTRACTThrough molecular subtyping, therapeutic vulnerabilities can be exploited for developing personalized medicine. The real utility of molecular subtyping lies in the clinical translation for disease characterization. Proteomic methods with defined marker sets hold great promise for improving therapy outcomes by improving the speed of predictions for devising treatment strategies.PMID:33853864 | DOI:10.1158/1078-0432.CCR-21-0640 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 15, 2021 Category: Cancer & Oncology Authors: Ravi Thakur Pankaj K Singh Source Type: research

Molecular Subtypes of Pancreatic Cancer: A Proteomics Approach
Clin Cancer Res. 2021 Apr 14:clincanres.0640.2021. doi: 10.1158/1078-0432.CCR-21-0640. Online ahead of print.ABSTRACTThrough molecular subtyping, therapeutic vulnerabilities can be exploited for developing personalized medicine. The real utility of molecular subtyping lies in the clinical translation for disease characterization. Proteomic methods with defined marker sets hold great promise for improving therapy outcomes by improving the speed of predictions for devising treatment strategies.PMID:33853864 | DOI:10.1158/1078-0432.CCR-21-0640 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 15, 2021 Category: Cancer & Oncology Authors: Ravi Thakur Pankaj K Singh Source Type: research

Selected Articles from This Issue
Clin Cancer Res. 2021 Apr 15;27(8):2121.NO ABSTRACTPMID:33849940 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 14, 2021 Category: Cancer & Oncology Source Type: research

Targeted deep sequencing of bladder tumors reveals novel associations between cancer gene mutations and mutational signatures with major risk factors
CONCLUSIONS: These data quantify the contribution of BC risk factors to mutational burden and suggest different signature enrichments among never, former, and current smokers.PMID:33849962 | DOI:10.1158/1078-0432.CCR-20-4419 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 14, 2021 Category: Cancer & Oncology Authors: Stella Koutros Nina Rao Lee Moore Michael L Nickerson Donghyuk Lee Bin Zhu Larissa Pardo Dalsu Baris Molly Schwenn Alison Johnson Kristine Jones Montserrat Garcia-Closas Ludmila Prokunina-Olsson Debra T Silverman Nathaniel Rothman Michael Dean Source Type: research

Phase 2 multicenter study of enzalutamide in metastatic castration resistant prostate cancer to identify mechanisms driving resistance
CONCLUSIONS: Our results demonstrate that a large proportion of enzalutamide-treated patients have baseline and progression alterations in the AR pathway and tumor suppressor genes. We demonstrate an increased number of BRCA2 alterations post-enzalutamide highlighting importance of serial tumor sampling in CRPC.PMID:33849963 | DOI:10.1158/1078-0432.CCR-20-4616 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 14, 2021 Category: Cancer & Oncology Authors: Rana R McKay Lucia Kwak Jett Crowdis Jamie M Sperger Shuang G Zhao Wanling Xie Lillian Werner Rosina T Lis Zhenwei Zhang Xiao X Wei Joshua M Lang Eliezer M Van Allen Rupal S Bhatt Evan Y Yu Peter S Nelson Glenn J Bubley Bruce Montgomery Mary-Ellen Taplin Source Type: research

Can biomarkers guide oncolytic virus immunotherapy?
Clin Cancer Res. 2021 Apr 13:clincanres.0660.2021. doi: 10.1158/1078-0432.CCR-21-0660. Online ahead of print.ABSTRACTDefects in tumor cell interferon-γ signaling is associated with resistance to immune checkpoint inhibitors. Recently, these defects were found to confer increased sensitivity to oncolytic virus infection. Differential expression of innate sensing elements in tumor cells may serve as predictive biomarkers of oncolytic virus immunotherapy in patients with cancer.PMID:33849964 | DOI:10.1158/1078-0432.CCR-21-0660 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 14, 2021 Category: Cancer & Oncology Authors: Howard L Kaufman Source Type: research

Selected Articles from This Issue
Clin Cancer Res. 2021 Apr 15;27(8):2121.NO ABSTRACTPMID:33849940 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 14, 2021 Category: Cancer & Oncology Source Type: research

Targeted deep sequencing of bladder tumors reveals novel associations between cancer gene mutations and mutational signatures with major risk factors
CONCLUSIONS: These data quantify the contribution of BC risk factors to mutational burden and suggest different signature enrichments among never, former, and current smokers.PMID:33849962 | DOI:10.1158/1078-0432.CCR-20-4419 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 14, 2021 Category: Cancer & Oncology Authors: Stella Koutros Nina Rao Lee Moore Michael L Nickerson Donghyuk Lee Bin Zhu Larissa Pardo Dalsu Baris Molly Schwenn Alison Johnson Kristine Jones Montserrat Garcia-Closas Ludmila Prokunina-Olsson Debra T Silverman Nathaniel Rothman Michael Dean Source Type: research

Phase 2 multicenter study of enzalutamide in metastatic castration resistant prostate cancer to identify mechanisms driving resistance
CONCLUSIONS: Our results demonstrate that a large proportion of enzalutamide-treated patients have baseline and progression alterations in the AR pathway and tumor suppressor genes. We demonstrate an increased number of BRCA2 alterations post-enzalutamide highlighting importance of serial tumor sampling in CRPC.PMID:33849963 | DOI:10.1158/1078-0432.CCR-20-4616 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 14, 2021 Category: Cancer & Oncology Authors: Rana R McKay Lucia Kwak Jett Crowdis Jamie M Sperger Shuang G Zhao Wanling Xie Lillian Werner Rosina T Lis Zhenwei Zhang Xiao X Wei Joshua M Lang Eliezer M Van Allen Rupal S Bhatt Evan Y Yu Peter S Nelson Glenn J Bubley Bruce Montgomery Mary-Ellen Taplin Source Type: research

Can biomarkers guide oncolytic virus immunotherapy?
Clin Cancer Res. 2021 Apr 13:clincanres.0660.2021. doi: 10.1158/1078-0432.CCR-21-0660. Online ahead of print.ABSTRACTDefects in tumor cell interferon-γ signaling is associated with resistance to immune checkpoint inhibitors. Recently, these defects were found to confer increased sensitivity to oncolytic virus infection. Differential expression of innate sensing elements in tumor cells may serve as predictive biomarkers of oncolytic virus immunotherapy in patients with cancer.PMID:33849964 | DOI:10.1158/1078-0432.CCR-21-0660 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 14, 2021 Category: Cancer & Oncology Authors: Howard L Kaufman Source Type: research

FDA Approval Summary: Pembrolizumab for the first-line treatment of patients with MSI-H/dMMR advanced unresectable or metastatic colorectal carcinoma
Clin Cancer Res. 2021 Apr 12:clincanres.0557.2021. doi: 10.1158/1078-0432.CCR-21-0557. Online ahead of print.ABSTRACTThe Food and Drug Administration (FDA) approved pembrolizumab on June 29, 2020, for the treatment of patients with unresectable or metastatic microsatellite instability-high (MSI-H) colorectal cancer (CRC) with no prior systemic treatment for advanced disease. The approval was based on data from Study Keynote-177, which randomly allocated patients to receive either pembrolizumab or standard of care (SOC) with chemotherapy. Overall survival (OS) and independently-assessed progression free survival (PFS) were ...
Source: Clinical Cancer Research - April 13, 2021 Category: Cancer & Oncology Authors: Sandra J Casak Leigh Marcus Lola Fashoyin-Aje Sirisha L Mushti Joyce Cheng Yuan Li Shen William F Pierce Leah Her Kirsten B Goldberg Marc R Theoret Paul G Kluetz Richard Pazdur Steven J Lemery Source Type: research

FDA Approval Summary: Pembrolizumab for the first-line treatment of patients with MSI-H/dMMR advanced unresectable or metastatic colorectal carcinoma
Clin Cancer Res. 2021 Apr 12:clincanres.0557.2021. doi: 10.1158/1078-0432.CCR-21-0557. Online ahead of print.ABSTRACTThe Food and Drug Administration (FDA) approved pembrolizumab on June 29, 2020, for the treatment of patients with unresectable or metastatic microsatellite instability-high (MSI-H) colorectal cancer (CRC) with no prior systemic treatment for advanced disease. The approval was based on data from Study Keynote-177, which randomly allocated patients to receive either pembrolizumab or standard of care (SOC) with chemotherapy. Overall survival (OS) and independently-assessed progression free survival (PFS) were ...
Source: Clinical Cancer Research - April 13, 2021 Category: Cancer & Oncology Authors: Sandra J Casak Leigh Marcus Lola Fashoyin-Aje Sirisha L Mushti Joyce Cheng Yuan Li Shen William F Pierce Leah Her Kirsten B Goldberg Marc R Theoret Paul G Kluetz Richard Pazdur Steven J Lemery Source Type: research

Myeloid Cell-associated Resistance to PD-1/PD-L1 Blockade in Urothelial Cancer Revealed Through Bulk and Single-cell RNA Sequencing
CONCLUSIONS: The balance of adaptive immunity and protumorigenic inflammation in individual tumor microenvironments is associated with PD-1/PD-L1 resistance in urothelial cancer with the latter linked to a proinflammatory cellular state of myeloid phagocytic cells detectable in tumor and blood.PMID:33837006 | DOI:10.1158/1078-0432.CCR-20-4574 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 10, 2021 Category: Cancer & Oncology Authors: Li Wang John P Sfakianos Kristin G Beaumont Guray Akturk Amir Horowitz Robert P Sebra Adam M Farkas Sacha Gnjatic Austin Hake Sudeh Izadmehr Peter Wiklund William K Oh Peter M Szabo Megan Wind-Rotolo Keziban Unsal-Kacmaz Xin Yao Eric Schadt Padmanee Sharm Source Type: research

Answers are in the Blood: cfDNA to Enhance Precision Medicine for Breast Cancer
Clin Cancer Res. 2021 Apr 9:clincanres.0353.2021. doi: 10.1158/1078-0432.CCR-21-0353. Online ahead of print.ABSTRACTIdentification of biomarkers to drive treatment using cell free DNA allows dynamic and safe assessment of tumor biology representing an important advance adding to tissue based genotyping. Caution must be exercised interpreting commercial matching information as validation is often lacking, and true matching is feasible in a minority of patients.PMID:33837007 | DOI:10.1158/1078-0432.CCR-21-0353 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 10, 2021 Category: Cancer & Oncology Authors: Hope S Rugo Laura Huppert Source Type: research

Myeloid Cell-associated Resistance to PD-1/PD-L1 Blockade in Urothelial Cancer Revealed Through Bulk and Single-cell RNA Sequencing
CONCLUSIONS: The balance of adaptive immunity and protumorigenic inflammation in individual tumor microenvironments is associated with PD-1/PD-L1 resistance in urothelial cancer with the latter linked to a proinflammatory cellular state of myeloid phagocytic cells detectable in tumor and blood.PMID:33837006 | DOI:10.1158/1078-0432.CCR-20-4574 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 10, 2021 Category: Cancer & Oncology Authors: Li Wang John P Sfakianos Kristin G Beaumont Guray Akturk Amir Horowitz Robert P Sebra Adam M Farkas Sacha Gnjatic Austin Hake Sudeh Izadmehr Peter Wiklund William K Oh Peter M Szabo Megan Wind-Rotolo Keziban Unsal-Kacmaz Xin Yao Eric Schadt Padmanee Sharm Source Type: research

Answers are in the Blood: cfDNA to Enhance Precision Medicine for Breast Cancer
Clin Cancer Res. 2021 Apr 9:clincanres.0353.2021. doi: 10.1158/1078-0432.CCR-21-0353. Online ahead of print.ABSTRACTIdentification of biomarkers to drive treatment using cell free DNA allows dynamic and safe assessment of tumor biology representing an important advance adding to tissue based genotyping. Caution must be exercised interpreting commercial matching information as validation is often lacking, and true matching is feasible in a minority of patients.PMID:33837007 | DOI:10.1158/1078-0432.CCR-21-0353 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 10, 2021 Category: Cancer & Oncology Authors: Hope S Rugo Laura Huppert Source Type: research

Myeloid Cell-associated Resistance to PD-1/PD-L1 Blockade in Urothelial Cancer Revealed Through Bulk and Single-cell RNA Sequencing
CONCLUSIONS: The balance of adaptive immunity and protumorigenic inflammation in individual tumor microenvironments is associated with PD-1/PD-L1 resistance in urothelial cancer with the latter linked to a proinflammatory cellular state of myeloid phagocytic cells detectable in tumor and blood.PMID:33837006 | DOI:10.1158/1078-0432.CCR-20-4574 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 10, 2021 Category: Cancer & Oncology Authors: Li Wang John P Sfakianos Kristin G Beaumont Guray Akturk Amir Horowitz Robert P Sebra Adam M Farkas Sacha Gnjatic Austin Hake Sudeh Izadmehr Peter Wiklund William K Oh Peter M Szabo Megan Wind-Rotolo Keziban Unsal-Kacmaz Xin Yao Eric Schadt Padmanee Sharm Source Type: research

Answers are in the Blood: cfDNA to Enhance Precision Medicine for Breast Cancer
Clin Cancer Res. 2021 Apr 9:clincanres.0353.2021. doi: 10.1158/1078-0432.CCR-21-0353. Online ahead of print.ABSTRACTIdentification of biomarkers to drive treatment using cell free DNA allows dynamic and safe assessment of tumor biology representing an important advance adding to tissue based genotyping. Caution must be exercised interpreting commercial matching information as validation is often lacking, and true matching is feasible in a minority of patients.PMID:33837007 | DOI:10.1158/1078-0432.CCR-21-0353 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 10, 2021 Category: Cancer & Oncology Authors: Hope S Rugo Laura Huppert Source Type: research

Phase 1 trial of N-803, an IL-15 receptor agonist, with rituximab in patients with indolent non-Hodgkin lymphoma
CONCLUSIONS: N-803 combines with mAbs to enhance tumor-targeting in patients, and warrants further investigation in combination with immunotherapies.PMID:33832946 | DOI:10.1158/1078-0432.CCR-20-4575 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 9, 2021 Category: Cancer & Oncology Authors: Jennifer A Foltz Brian T Hess Veronika Bachanova Nancy L Bartlett Melissa M Berrien-Elliott Ethan McClain Michelle K Becker-Hapak Mark Foster Timothy Schappe Brad Kahl Neha Mehta-Shah Amanda F Cashen Nancy D Marin Kristen McDaniels Chaz Moreno Matthew Mos Source Type: research

Plasma KIM-1 is associated with recurrence risk after nephrectomy for localized renal cell carcinoma: A trial of the ECOG-ACRIN Research Group (E2805)
Clin Cancer Res. 2021 Apr 8:clincanres.0025.2021. doi: 10.1158/1078-0432.CCR-21-0025. Online ahead of print.ABSTRACTPURPOSE: No circulating biomarkers are currently available to identify patients at highest risk of recurrence after nephrectomy for renal cell carcinoma (RCC). Kidney injury molecule-1 (KIM-1) is overexpressed in RCC and its ectodomain circulates in plasma. We investigated whether plasma KIM-1 is a prognostic biomarker in patients with localized RCC after nephrectomy.EXPERIMENTAL DESIGN: The ECOG-ACRIN E2805 (ASSURE) trial evaluated adjuvant sunitinib, sorafenib, or placebo in resected high-risk RCC. KIM-1 le...
Source: Clinical Cancer Research - April 9, 2021 Category: Cancer & Oncology Authors: Wenxin Xu Maneka Puligandla Brian Halbert Naomi B Haas Keith T Flaherty Robert G Uzzo Janice P Dutcher Robert S DiPaola Venkata Sabbisetti Rupal S Bhatt Source Type: research

Anti-CLL1 chimeric antigen receptor T cell therapy in children with relapsed/refractory acute myeloid leukemia
CONCLUSIONS: Based on our single-institution experience, autologous anti-CLL1 CAR-T cell therapy has the potential to be a safe and efficient alternative treatment for children with R/R-AML, and therefore requires further investigation.PMID:33832948 | DOI:10.1158/1078-0432.CCR-20-4543 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 9, 2021 Category: Cancer & Oncology Authors: Hui Zhang Pengfei Wang Zhuoyan Li Yingyi He Wenting Gan Hua Jiang Source Type: research

Anlotinib in Locally Advanced or Metastatic Medullary Thyroid Carcinoma: A Randomized, Double-Blind Phase IIB Trial
CONCLUSION: Anlotinib demonstrates its efficacy and safety in this phase ⅡB trial for the treatment of MTC and may become a new choice for this rare disease, especially for Chinese patients.PMID:33832949 | DOI:10.1158/1078-0432.CCR-20-2950 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 9, 2021 Category: Cancer & Oncology Authors: Dapeng Li Yihebali Chi Xiaohong Chen Ming-Hua Ge Yuan Zhang Zhuming Guo Jun Wang Jie Chen Jiewu Zhang Ying Cheng Zhendong Li Hui Liu Jianwu Qin Jingqiang Zhu Ruochuan Cheng Zhengang Xu Xiangqian Zheng Pingzhang Tang Ming Gao Source Type: research

Tumor Immune Microenvironment during Epithelial-Mesenchymal Transition
Clin Cancer Res. 2021 Apr 7:clincanres.4459.2020. doi: 10.1158/1078-0432.CCR-20-4459. Online ahead of print.ABSTRACTEpithelial-mesenchymal transition (EMT) has been shown to play a critical role in tumor development from initiation to metastasis. EMT could be regarded as a continuum, with intermediate hybrid epithelial and mesenchymal phenotypes having high plasticity. Classical EMT is characterized by the phenotype change of epithelial cells to cells with mesenchymal properties, but EMT is also associated with multiple other molecular processes, including tumor immune evasion. Some previous studies have shown that EMT is ...
Source: Clinical Cancer Research - April 8, 2021 Category: Cancer & Oncology Authors: Mana Taki Kaoru Abiko Masayo Ukita Ryusuke Murakami Koji Yamanoi Ken Yamaguchi Junzo Hamanishi Tsukasa Baba Noriomi Matsumura Masaki Mandai Source Type: research

Tumor Immune Microenvironment during Epithelial-Mesenchymal Transition
Clin Cancer Res. 2021 Apr 7:clincanres.4459.2020. doi: 10.1158/1078-0432.CCR-20-4459. Online ahead of print.ABSTRACTEpithelial-mesenchymal transition (EMT) has been shown to play a critical role in tumor development from initiation to metastasis. EMT could be regarded as a continuum, with intermediate hybrid epithelial and mesenchymal phenotypes having high plasticity. Classical EMT is characterized by the phenotype change of epithelial cells to cells with mesenchymal properties, but EMT is also associated with multiple other molecular processes, including tumor immune evasion. Some previous studies have shown that EMT is ...
Source: Clinical Cancer Research - April 8, 2021 Category: Cancer & Oncology Authors: Mana Taki Kaoru Abiko Masayo Ukita Ryusuke Murakami Koji Yamanoi Ken Yamaguchi Junzo Hamanishi Tsukasa Baba Noriomi Matsumura Masaki Mandai Source Type: research

A PERFECT biomarker-focused study of neoadjuvant IO for esophagogastric cancer
Clin Cancer Res. 2021 Apr 6:clincanres.0324.2021. doi: 10.1158/1078-0432.CCR-21-0324. Online ahead of print.ABSTRACTTo evaluate feasibility and efficacy, checkpoint inhibitor atezolizumab was added to neoadjuvant chemoradiotherapy prior to surgery for esophagogastric adenocarcinoma. The approach was deemed feasible, and while it did not demonstrate better clinical outcome to propensity-matched patients, biomarker investigation demonstrated that high inflammation in the sample at baseline predicted therapeutic benefit.PMID:33824165 | DOI:10.1158/1078-0432.CCR-21-0324 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 7, 2021 Category: Cancer & Oncology Authors: Daniel V T Catenacci Source Type: research

The anti-HER3 monoclonal antibody seribantumab effectively inhibits growth of patient-derived and isogenic cell line and xenograft models with oncogenic < em > NRG1 < /em > fusions
CONCLUSION: Seribantumab treatment blocked activation of the four ERBB family members and of downstream signaling, leading to inhibition of NRG1 fusion-dependent tumorigenesis in vitro and in vivo in breast, lung and ovarian patient-derived cancer models.PMID:33824166 | DOI:10.1158/1078-0432.CCR-20-3605 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 7, 2021 Category: Cancer & Oncology Authors: Igor Odintsov Allan Jw Lui Whitney J Sisso Eric G Gladstone Zebing Liu Lukas Delasos Renate I Kurth Exequiel M Sisso Morana Vojnic Inna Khodos Marissa Mattar Elisa de Stanchina Shawn M Leland Marc Ladanyi Romel Somwar Source Type: research

A PERFECT biomarker-focused study of neoadjuvant IO for esophagogastric cancer
Clin Cancer Res. 2021 Apr 6:clincanres.0324.2021. doi: 10.1158/1078-0432.CCR-21-0324. Online ahead of print.ABSTRACTTo evaluate feasibility and efficacy, checkpoint inhibitor atezolizumab was added to neoadjuvant chemoradiotherapy prior to surgery for esophagogastric adenocarcinoma. The approach was deemed feasible, and while it did not demonstrate better clinical outcome to propensity-matched patients, biomarker investigation demonstrated that high inflammation in the sample at baseline predicted therapeutic benefit.PMID:33824165 | DOI:10.1158/1078-0432.CCR-21-0324 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 7, 2021 Category: Cancer & Oncology Authors: Daniel V T Catenacci Source Type: research

The anti-HER3 monoclonal antibody seribantumab effectively inhibits growth of patient-derived and isogenic cell line and xenograft models with oncogenic < em > NRG1 < /em > fusions
CONCLUSION: Seribantumab treatment blocked activation of the four ERBB family members and of downstream signaling, leading to inhibition of NRG1 fusion-dependent tumorigenesis in vitro and in vivo in breast, lung and ovarian patient-derived cancer models.PMID:33824166 | DOI:10.1158/1078-0432.CCR-20-3605 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 7, 2021 Category: Cancer & Oncology Authors: Igor Odintsov Allan Jw Lui Whitney J Sisso Eric G Gladstone Zebing Liu Lukas Delasos Renate I Kurth Exequiel M Sisso Morana Vojnic Inna Khodos Marissa Mattar Elisa de Stanchina Shawn M Leland Marc Ladanyi Romel Somwar Source Type: research

Sapanisertib Plus Exemestane or Fulvestrant in Women with Hormone Receptor-Positive/HER2-Negative Advanced or Metastatic Breast Cancer
CONCLUSIONS: Sapanisertib plus exemestane or fulvestrant was well tolerated and exhibited clinical benefit in postmenopausal women with pretreated everolimus-sensitive or everolimus-resistant breast cancer.PMID:33820779 | DOI:10.1158/1078-0432.CCR-20-4131 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 6, 2021 Category: Cancer & Oncology Authors: Bora Lim David A Potter Mohamad A Salkeni Paula Silverman Tufia C Haddad Frederic Forget Ahmad Awada Jean-Luc Canon Michael Danso Alain Lortholary Hugues Bourgeois Elizabeth Tan-Chiu Sylvie Vincent Brittany Bahamon Kevin J Galinsky Chirag Patel Rachel Neu Source Type: research

First-in-Human Phase 1 Study of ABBV-085, an Antibody-Drug Conjugate Targeting LRRC15, in Sarcomas and Other Advanced Solid Tumors
CONCLUSIONS: ABBV-085 appeared safe and tolerable at a dose of 3.6 mg/kg every 14 days, with preliminary antitumor activity noted in patients with osteosarcoma and UPS. Given the high unmet need in these orphan malignancies, further investigation into targeting LRRC15 in these sarcomas may be warranted.PMID:33820780 | DOI:10.1158/1078-0432.CCR-20-4513 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 6, 2021 Category: Cancer & Oncology Authors: George D Demetri Jason J Luke Antoine Hollebecque John Powderly Alexander I Spira Vivek Subbiah Louie Naumovski Chris Chen Hua Fang Dominic W Lai Huibin Yue Akshanth R Polepally James W Purcell Randy Robinson Padmanee Sharma James P Allison Anthony W Tolc Source Type: research

Standardized Uptake Value for 18F-Fluorodeoxyglucose is a Marker of Inflammatory State and Immune Infiltrate in Cervical Cancer
Clin Cancer Res. 2021 Apr 5:clincanres.4450.2020. doi: 10.1158/1078-0432.CCR-20-4450. Online ahead of print.ABSTRACTPURPOSE: Chemo-radiotherapy for locally advanced cervical cancer fails in over a third of patients. Biomarkers with therapeutic implications are therefore needed. We investigated the relationship between an established prognostic marker, maximum standardized uptake value (SUVmax) on 18F-fluorodeoxyglucose positron emission tomography, and the inflammatory and immune state of cervical cancers.EXPERIMENTAL DESIGN: An SUVmax most prognostic for freedom from progression (FFP) was identified and compared to known ...
Source: Clinical Cancer Research - April 6, 2021 Category: Cancer & Oncology Authors: John M Floberg Jin Zhang Naoshad Muhammad Todd A DeWees Matthew Inkman Kevin Chen Alexander J Lin Ramachandran Rashmi Kay Jayachandran Brian T Edelson Barry A Siegel Farrokh Dehdashti Perry W Grigsby Stephanie Markovina Julie K Schwarz Source Type: research

Circulating tumor cell chromosomal instability and neuroendocrine phenotype by immunomorphology and poor outcomes in men with mCRPC treated with abiraterone or enzalutamide
CONCLUSIONS: A high chromosomal instability and neuroendocrine CTC phenotype is independently associated with worse survival in men with mCRPC treated with abi/enza, warranting further prospective controlled predictive studies to inform treatment decisions.PMID:33820782 | DOI:10.1158/1078-0432.CCR-20-3471 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 6, 2021 Category: Cancer & Oncology Authors: Landon C Brown Susan Halabi Joseph D Schonhoft Qian Yang Jun Luo David M Nanus Paraskevi Giannakakou Russell Z Szmulewitz Daniel C Danila Ethan S Barnett Emily A Carbone Jimmy L Zhao Patrick Healy Monika Anand Audrey Gill Adam Jendrisak William R Berry Sa Source Type: research

A Phase 1b/2 Study of Pepinemab in Combination with Avelumab in Advanced Non-Small Cell Lung Cancer
CONCLUSIONS: The combination of pepinemab with avelumab was well tolerated in NSCLC and showed signs of antitumor activity in immunotherapy resistant and PD-L1 negative / low tumors.PMID:33820783 | DOI:10.1158/1078-0432.CCR-20-4792 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 6, 2021 Category: Cancer & Oncology Authors: Michael Shafique Terrence Lee Fisher Elizabeth E Evans John E Leonard Desa Rae Electa Pastore Crystal L Mallow Ernest S Smith Vikas Mishra Andreas Schr öder Kevin Chin J Thaddeus Beck Megan Ann Baumgart Ramaswamy Govindan Nashat Y Gabrail Alexander I Spi Source Type: research

Pilot Clinical Trial of Perioperative Durvalumab and Tremelimumab in the Treatment of Resectable Colorectal Cancer Liver Metastases
CONCLUSIONS: This study demonstrates the safety of neoadjuvant combination tremelimumab and durvalumab prior to CRC liver resection. Evidence for T and B cell activation following this therapy was seen in pMMR mCRC.PMID:33811152 | DOI:10.1158/1078-0432.CCR-21-0163 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 3, 2021 Category: Cancer & Oncology Authors: Preeti Kanikarla Marie Cara Haymaker Edwin R Parra Young Uk Kim Rossana Lazcano Swati Gite Daniele Lorenzini Ignacio I Wistuba Rebecca S S Tidwell Xiaofei Song Wai Chin Foo Dipen M Maru Yun Shin Chun P Andrew Futreal Bryan Kee David Menter Luisa M Solis C Source Type: research

A Pan-Histone Deacetylase Inhibitor Enhances the Antitumor Activity of B7-H3-specific CAR-T Cells in Solid Tumors
CONCLUSIONS: Our results show that our novel strategy which combines SAHA and B7-H3.CAR-T cells enhances their therapeutic efficacy with solid cancers and justify its translation to a clinical setting.PMID:33811153 | DOI:10.1158/1078-0432.CCR-20-2487 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 3, 2021 Category: Cancer & Oncology Authors: Xinyuan Lei Zhanpeng Ou Zhaohui Yang Jianglong Zhong Yanliang Zhu Jing Tian Jiannan Wu Heran Deng Xinyu Lin Yu Peng Bowen Li Lile He Zhiming Tu Weixiong Chen Qunxing Li Niu Liu Hanqing Zhang Zhangsong Wang Zezhen Fang Teppei Yamada Xiaobin Lv Tian Tian Gu Source Type: research

Pilot Clinical Trial of Perioperative Durvalumab and Tremelimumab in the Treatment of Resectable Colorectal Cancer Liver Metastases
CONCLUSIONS: This study demonstrates the safety of neoadjuvant combination tremelimumab and durvalumab prior to CRC liver resection. Evidence for T and B cell activation following this therapy was seen in pMMR mCRC.PMID:33811152 | DOI:10.1158/1078-0432.CCR-21-0163 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 3, 2021 Category: Cancer & Oncology Authors: Preeti Kanikarla Marie Cara Haymaker Edwin R Parra Young Uk Kim Rossana Lazcano Swati Gite Daniele Lorenzini Ignacio I Wistuba Rebecca S S Tidwell Xiaofei Song Wai Chin Foo Dipen M Maru Yun Shin Chun P Andrew Futreal Bryan Kee David Menter Luisa M Solis C Source Type: research

A Pan-Histone Deacetylase Inhibitor Enhances the Antitumor Activity of B7-H3-specific CAR-T Cells in Solid Tumors
CONCLUSIONS: Our results show that our novel strategy which combines SAHA and B7-H3.CAR-T cells enhances their therapeutic efficacy with solid cancers and justify its translation to a clinical setting.PMID:33811153 | DOI:10.1158/1078-0432.CCR-20-2487 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 3, 2021 Category: Cancer & Oncology Authors: Xinyuan Lei Zhanpeng Ou Zhaohui Yang Jianglong Zhong Yanliang Zhu Jing Tian Jiannan Wu Heran Deng Xinyu Lin Yu Peng Bowen Li Lile He Zhiming Tu Weixiong Chen Qunxing Li Niu Liu Hanqing Zhang Zhangsong Wang Zezhen Fang Teppei Yamada Xiaobin Lv Tian Tian Gu Source Type: research

Pilot Clinical Trial of Perioperative Durvalumab and Tremelimumab in the Treatment of Resectable Colorectal Cancer Liver Metastases
CONCLUSIONS: This study demonstrates the safety of neoadjuvant combination tremelimumab and durvalumab prior to CRC liver resection. Evidence for T and B cell activation following this therapy was seen in pMMR mCRC.PMID:33811152 | DOI:10.1158/1078-0432.CCR-21-0163 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 3, 2021 Category: Cancer & Oncology Authors: Preeti Kanikarla Marie Cara Haymaker Edwin R Parra Young Uk Kim Rossana Lazcano Swati Gite Daniele Lorenzini Ignacio I Wistuba Rebecca S S Tidwell Xiaofei Song Wai Chin Foo Dipen M Maru Yun Shin Chun P Andrew Futreal Bryan Kee David Menter Luisa M Solis C Source Type: research

A Pan-Histone Deacetylase Inhibitor Enhances the Antitumor Activity of B7-H3-specific CAR-T Cells in Solid Tumors
CONCLUSIONS: Our results show that our novel strategy which combines SAHA and B7-H3.CAR-T cells enhances their therapeutic efficacy with solid cancers and justify its translation to a clinical setting.PMID:33811153 | DOI:10.1158/1078-0432.CCR-20-2487 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 3, 2021 Category: Cancer & Oncology Authors: Xinyuan Lei Zhanpeng Ou Zhaohui Yang Jianglong Zhong Yanliang Zhu Jing Tian Jiannan Wu Heran Deng Xinyu Lin Yu Peng Bowen Li Lile He Zhiming Tu Weixiong Chen Qunxing Li Niu Liu Hanqing Zhang Zhangsong Wang Zezhen Fang Teppei Yamada Xiaobin Lv Tian Tian Gu Source Type: research

Phase I trial of MEDI3726, a prostate-specific membrane antigen-targeted antibody-drug conjugate, in patients with mCRPC after failure of abiraterone or enzalutamide
Clin Cancer Res. 2021 Apr 1:clincanres.4528.2020. doi: 10.1158/1078-0432.CCR-20-4528. Online ahead of print.ABSTRACTPURPOSE: MEDI3726 is an antibody-drug conjugate targeting the prostate-specific membrane antigen and carrying a pyrrolobenzodiazepine warhead. This Phase 1 study evaluated MEDI3726 monotherapy in patients with metastatic castration-resistant prostate cancer after disease progression on abiraterone and/or enzalutamide and taxane-based chemotherapy.EXPERIMENTAL DESIGN: MEDI3726 was administered at 0.015-0.3 mg/kg IV Q3W until disease progression/unacceptable toxicity. The primary objective was to assess safety,...
Source: Clinical Cancer Research - April 2, 2021 Category: Cancer & Oncology Authors: Johann S de Bono Mark T Fleming Judy S Wang Richard Cathomas Manuel Selvi Miralles John Bothos Mary Jane Hinrichs Qu Zhang Peng He Marna Williams Anton I Rosenbaum Meina Liang Kapil Vashisht Song Cho Pablo Martinez Daniel P Petrylak Source Type: research

Next-Generation Sequencing of 487 Esophageal Adenocarcinomas Reveals Independently Prognostic Genomic Driver Alterations and Pathways
CONCLUSIONS: Our study suggests that higher levels of genomic instability are associated with more advanced disease in esophageal adenocarcinoma. Furthermore, CDKN2A, KRAS, and SMAD4 represent prognostic biomarkers, given their strong association with poor survival.PMID:33795256 | DOI:10.1158/1078-0432.CCR-20-4707 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 2, 2021 Category: Cancer & Oncology Authors: Smita Sihag Samuel C Nussenzweig Henry Walch Meier Hsu Kay See Tan Francisco Sanchez-Vega Walid K Chatila Sergio A De La Torre Assem Patel Yelena Y Janjigian Steven B Maron Geoffrey Y Ku Laura H Tang Jaclyn F Hechtman Pari M Shah Abraham J Wu David R Jone Source Type: research

Molecular biomarkers of response to eribulin in patients with leiomyosarcoma
CONCLUSIONS: LMS has a complex genetic background, with multiple CNA and mutations affecting genes implicated in tumorigenesis. We identified several molecular changes with potential impact on survival of LMS patients when treated with eribulin.PMID:33795257 | DOI:10.1158/1078-0432.CCR-20-4315 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 2, 2021 Category: Cancer & Oncology Authors: Agnieszka Wozniak Bram Boeckx Elodie Modave Amy A Weaver Diether Lambrechts Bruce A Littlefield Patrick Sch öffski Source Type: research

Female immunity protects from cutaneous squamous cell carcinoma
CONCLUSIONS: This work shows the immune response is sex biased in cSCC,and highlights female immunity offers greater protection than male immunity.PMID:33795258 | DOI:10.1158/1078-0432.CCR-20-4261 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 2, 2021 Category: Cancer & Oncology Authors: Timothy Budden Caroline Gaudy-Marqueste Sarah Craig Yuan Hu Charles Earnshaw Shilpa Gurung Amelle Ra Victoria Akhras Patrick Shenjere Ruth Green Lynne Jamieson John Lear Luisa Motta Carlos Caulin Deemesh Oudit Simon J Furney Amaya Viros Source Type: research

Liquid Biopsy: It's the Bloody Truth!
Clin Cancer Res. 2021 Apr 1:clincanres.0531.2021. doi: 10.1158/1078-0432.CCR-21-0531. Online ahead of print.ABSTRACTLiquid biopsy is a promising clinical tool that can provide critical information for prognostication and which may inform treatment decisions in men with metastatic castration resistant prostate cancer (mCRPC). Here we discuss the Foundation Medicine plasma cell free tumor DNA (ctDNA) assay, its pros and cons, and potential clinical utility.PMID:33795259 | DOI:10.1158/1078-0432.CCR-21-0531 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - April 2, 2021 Category: Cancer & Oncology Authors: Nathan M Hawkey Andrew J Armstrong Source Type: research