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1. Deep learning of cell spatial organizations identifies clinically relevant insights in tissue images

Author

Shidan Wang, Ruichen Rong, Qin Zhou, Donghan M. Yang, Xinyi Zhang, Xiaowei Zhan, Justin Bishop, Zhikai Chi, Clare J. Wilhelm, Siyuan Zhang, Curtis R. Pickering, Mark G. Kris, John Minna, Yang Xie, and Guanghua Xiao

Subjects
Science
Abstract

Abstract Recent advancements in tissue imaging techniques have facilitated the visualization and identification of various cell types within physiological and pathological contexts. Despite the emergence of cell-cell interaction studies, there is a lack of methods for evaluating individual spatial interactions. In this study, we introduce Ceograph, a cell spatial organization-based graph convolutional network designed to analyze cell spatial organization (for example,. the cell spatial distribution, morphology, proximity, and interactions) derived from pathology images. Ceograph identifies key cell spatial organization features by accurately predicting their influence on patient clinical outcomes. In patients with oral potentially malignant disorders, our model highlights reduced structural concordance and increased closeness in epithelial substrata as driving features for an elevated risk of malignant transformation. In lung cancer patients, Ceograph detects elongated tumor nuclei and diminished stroma-stroma closeness as biomarkers for insensitivity to EGFR tyrosine kinase inhibitors. With its potential to predict various clinical outcomes, Ceograph offers a deeper understanding of biological processes and supports the development of personalized therapeutic strategies.

Published
2023
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2. ctDNA-based detection of molecular residual disease in stage I-III non-small cell lung cancer patients treated with definitive radiotherapy

Author

Emily S. Lebow, Narek Shaverdian, Jordan E. Eichholz, Leah B. Kratochvil, Megan McCune, Yonina R. Murciano-Goroff, Justin Jee, Juliana Eng, Jamie E. Chaft, Mark G. Kris, Ekaterina Kalashnikova, Jordan Feeney, Carly Bess Scalise, Sumedha Sudhaman, Charuta C. Palsuledesai, Meenakshi Malhotra, Michael Krainock, Himanshu Sethi, Alexey Aleshin, Minetta C. Liu, Annemarie F. Shepherd, Abraham J. Wu, Charles B. Simone, Daphna Y. Gelblum, Kaylie A. Johnson, Charles M. Rudin, Daniel R. Gomez, Pedram Razavi, Jorge S. Reis-Filho, James M. Isbell, Bob T. Li, and Andreas Rimner

Subjects
circulating tumor DNA (ctDNA), tumor-informed, molecular residual disease (MRD), non-small cell lung cancer (NSCLC), definitive radiation, prognostic biomarker, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

BackgroundSensitive and reliable biomarkers for early detection of recurrence are needed to improve post-definitive radiation risk stratification, disease management, and outcomes for patients with unresectable early-stage or locally advanced non-small cell lung cancer (NSCLC) who are treated with definitive radiation therapy (RT). This prospective, multistate single-center, cohort study investigated the association of circulating tumor DNA (ctDNA) status with recurrence in patients with unresectable stage I-III NSCLC who underwent definitive RT.MethodsA total of 70 serial plasma samples from 17 NSCLC patients were collected before, during, and after treatment. A personalized, tumor-informed ctDNA assay was used to track a set of up to 16 somatic, single nucleotide variants in the associated patient’s plasma samples.ResultsPre-treatment ctDNA detection rate was 82% (14/17) and varied based on histology and stage. ctDNA was detected in 35% (6/17) of patients at the first post-RT timepoint (median of 1.66 months following the completion of RT), all of whom subsequently developed clinical progression. At this first post-RT time point, patients with ctDNA-positivity had significantly worse progression-free survival (PFS) [hazard ratio (HR): 24.2, p=0.004], and ctDNA-positivity was the only significant prognostic factor associated with PFS (HR: 13.4, p=0.02) in a multivariate analysis. All patients who developed clinical recurrence had detectable ctDNA with an average lead time over radiographic progression of 5.4 months, and post-RT ctDNA positivity was significantly associated with poor PFS (p

Published
2023
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3. Phase I trial of the TNF-α inhibitor certolizumab plus chemotherapy in stage IV lung adenocarcinomas

Author

Paul K. Paik, Jia Luo, Ni Ai, Rachel Kim, Linda Ahn, Anup Biswas, Courtney Coker, Wanchao Ma, Phillip Wong, Darren J. Buonocore, W. Victoria Lai, Jamie E. Chaft, Swarnali Acharyya, Joan Massagué, and Mark G. Kris

Subjects
Science
Abstract

Generation of TNF-α in response to chemotherapy has been associated with chemo-resistance and metastasis propagation. Here the authors show that the combination of an anti-TNF antibody and cisplatin doublet chemotherapy increases anti-tumor efficacy in lung cancer preclinical models and report the results of a phase I clinical trial of the anti-TNF-α antibody certolizumab in combination with chemotherapy in patients with stage IV lung adenocarcinomas.

Published
2022
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4. Features of tumor-microenvironment images predict targeted therapy survival benefit in patients with EGFR-mutant lung cancer

Author

Shidan Wang, Ruichen Rong, Donghan M. Yang, Junya Fujimoto, Justin A. Bishop, Shirley Yan, Ling Cai, Carmen Behrens, Lynne D. Berry, Clare Wilhelm, Dara Aisner, Lynette Sholl, Bruce E. Johnson, David J. Kwiatkowski, Ignacio I. Wistuba, Paul A. Bunn Jr., John Minna, Guanghua Xiao, Mark G. Kris, and Yang Xie

Subjects
Oncology, Medicine
Abstract

Tyrosine kinase inhibitors (TKIs) targeting epidermal growth factor receptor (EGFR) are effective for many patients with lung cancer with EGFR mutations. However, not all patients are responsive to EGFR TKIs, including even those harboring EGFR-sensitizing mutations. In this study, we quantified the cells and cellular interaction features of the tumor microenvironment (TME) using routine H&E-stained biopsy sections. These TME features were used to develop a prediction model for survival benefit from EGFR TKI therapy in patients with lung adenocarcinoma and EGFR-sensitizing mutations in the Lung Cancer Mutation Consortium 1 (LCMC1) and validated in an independent LCMC2 cohort. In the validation data set, EGFR TKI treatment prolonged survival in the predicted-to-benefit group but not in the predicted-not-to-benefit group. Among patients treated with EGFR TKIs, the predicted-to-benefit group had prolonged survival outcomes compared with the predicted not-to-benefit group. The EGFR TKI survival benefit positively correlated with tumor-tumor interaction image features and negatively correlated with tumor-stroma interaction. Moreover, the tumor-stroma interaction was associated with higher activation of the hepatocyte growth factor/MET-mediated PI3K/AKT signaling pathway and epithelial-mesenchymal transition process, supporting the hypothesis of fibroblast-involved resistance to EGFR TKI treatment.

Published
2023
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5. Phase 1 Clinical Trial of Trametinib and Ponatinib in Patients With NSCLC Harboring KRAS Mutations

Author

Kathryn C. Arbour, MD, Eusebio Manchado, PhD, Matthew J. Bott, MD, Linda Ahn, NP, Yosef Tobi, BA, Andy Ai Ni, Helena A. Yu, MD, Alyssa Shannon, BA, Marc Ladanyi, MD, Victoria Perron, BS, Michelle S. Ginsberg, MD, Amanda Johnson, BA, Andrei Holodny, MD, Mark G. Kris, MD, Charles M. Rudin, MD, PhD, Piro Lito, MD, PhD, Neal Rosen, MD, PhD, Scott Lowe, PhD, and Gregory J. Riely, MD, PhD

Subjects
NSCLC, KRAS, targeted therapy, MEK, FGFR1, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Introduction: Somatic KRAS mutations occur in 25% of patients with NSCLC. Treatment with MEK inhibitor monotherapy has not been successful in clinical trials to date. Compensatory activation of FGFR1 was identified as a mechanism of trametinib resistance in KRAS-mutant NSCLC, and combination therapy with trametinib and ponatinib was synergistic in in vitro and in vivo models. This study sought to evaluate this drug combination in patients with KRAS-mutant NSCLC. Methods: A phase 1 dose escalation study of trametinib and ponatinib was conducted in patients with advanced NSCLC with KRAS mutations. A standard 3-plus-3 dose escalation was done. Patients were treated with the study therapy until intolerable toxicity or disease progression. Results: A total of 12 patients with KRAS-mutant NSCLC were treated (seven at trametinib 2 mg and ponatinib 15 mg, five at trametinib 2 mg and ponatinib 30 mg). Common toxicities observed were rash, diarrhea, and fever. Serious adverse events potentially related to therapy were reported in five patients, including one death in the study and four cardiovascular events. Serious events were observed at both dose levels. Of note, 75% (9 of 12) were assessable for radiographic response and no confirmed partial responses were observed. The median time on study was 43 days. Conclusions: In this phase 1 study, in patients with KRAS-mutant advanced NSCLC, combined treatment with trametinib and ponatinib was associated with cardiovascular and bleeding toxicities. Exploring the combination of MEK and FGFR1 inhibition in future studies is potentially warranted but alternative agents should be considered to improve safety and tolerability.

Published
2022
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6. Targeting the differential addiction to anti-apoptotic BCL-2 family for cancer therapy

Author

Akane Inoue-Yamauchi, Paul S. Jeng, Kwanghee Kim, Hui-Chen Chen, Song Han, Yogesh Tengarai Ganesan, Kota Ishizawa, Sylvia Jebiwott, Yiyu Dong, Maria C. Pietanza, Matthew D. Hellmann, Mark G. Kris, James J. Hsieh, and Emily H. Cheng

Subjects
Science
Abstract

Small cell lung cancer cells (SCLC) are differentially sensitive to inhibitors of the BCL-2 family. Here the authors analyse the response to BH3 mimetics in SCLC, delineate patterns of expression of apoptotic proteins correlated with differential sensitivities and demonstrate a synergistic anti-tumour activity between ABT-199 and anthracyclines or CDK9 inhibitors.

Published
2017
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7. Molecular Biomarkers of Disease Outcomes and Mechanisms of Acquired Resistance to First-Line Osimertinib in Advanced EGFR-Mutant Lung Cancers

Author

Noura J. Choudhury, Antonio Marra, Jane S.Y. Sui, Jessica Flynn, Soo-Ryum Yang, Christina J. Falcon, Pier Selenica, Adam J. Schoenfeld, Natasha Rekhtman, Daniel Gomez, Michael F. Berger, Marc Ladanyi, Maria Arcila, Charles M. Rudin, Gregory J. Riely, Mark G. Kris, Glenn Heller, Jorge S. Reis-Filho, and Helena A. Yu

Subjects
Pulmonary and Respiratory Medicine, Oncology
Abstract

Preferred first-line treatment for patients with metastatic EGFR-mutant lung cancer is osimertinib, yet it is not known if patient outcomes may be improved by identifying and intervening upon molecular markers associated with therapeutic resistance.All patients with metastatic EGFR-mutant lung cancer treated with first-line osimertinib at Memorial Sloan Kettering Cancer Center (n=327) were identified. Available pre-treatment and post-progression tumor samples underwent targeted gene panel sequencing and mutational signature analysis using SigMA algorithm. Progression-free and overall survival were estimated using Kaplan Meier methods.Using multivariate analysis, baseline atypical EGFR (mPFS 5.8 mo, p0.001) and concurrent TP53/RB1 alterations (mPFS 10.5 mo, p=0.015) were associated with shorter progression-free survival on first-line osimertinib. Of 95 patients with post-progression biopsies, acquired resistance mechanisms were identified in 52% (off-target n=24, histological transformation n=14, on-target n=12), with MET amplification (n=9), small cell lung transformation (n=7) and acquired EGFR amplification (n=7) the most frequently identified mechanisms. While there was no difference in post-progression survival based on identified resistance (p=0.07), patients with subsequent second-line therapy tailored to post-progression biopsy results had improved post-progression survival (HR 0.09, p=0.006). Paired post-progression tumors had higher tumor mutational burden (p=0.008) and further dominant APOBEC mutational signatures (p=0.07) compared to pre-treatment samples.Patients with EGFR-mutant lung cancer treated with first-line osimertinib have improved survival with treatment adaptation based on identified mechanisms of resistance at time of progression using tissue-based genomic analysis. Further survival gains may be achieved using risk-based treatment adaptation of pre-treatment genomic alterations.

Published
2023

9. Brief Report: Combination of Osimertinib and Dacomitinib to Mitigate Primary and Acquired Resistance in EGFR-Mutant Lung Adenocarcinomas

Author

Arielle Elkrief, Alex Makhnin, Khadeja A. Moses, Linda S. Ahn, Isabel R. Preeshagul, Afsheen N. Iqbal, Sara A. Hayes, Andrew J. Plodkowski, Paul K. Paik, Marc Ladanyi, Mark G. Kris, Gregory J. Riely, Franziska Michor, and Helena A. Yu

Subjects
Cancer Research, Oncology
Abstract

Purpose: Primary and acquired resistance to osimertinib remain significant challenges for patients with EGFR-mutant lung cancers. Acquired EGFR alterations such as EGFR T790M or C797S mediate resistance to EGFR tyrosine kinase inhibitors (TKI) and combination therapy with dual EGFR TKIs may prevent or reverse on-target resistance. Patients and Methods: We conducted two prospective, phase I/II trials assessing combination osimertinib and dacomitinib to address on-target resistance in the primary and acquired resistance settings. In the initial therapy study, patients received dacomitinib and osimertinib in combination as initial therapy. In the acquired resistance trial, dacomitinib with or without osimertinib was administered to patients with EGFR-mutant lung cancers with disease progression on osimertinib alone and evidence of an acquired EGFR second-site mutation. Results: Cutaneous toxicities occurred in 93% (any grade) of patients and diarrhea in 72% (any grade) with the combination. As initial therapy, the overall response to the combination was 73% [95% confidence interval (CI), 50%–88%]. No acquired secondary alterations in EGFR were observed in any patients at progression. In the acquired resistance setting, the overall response was 14% (95% CI, 1%–58%). Conclusions: We observed no acquired secondary EGFR alterations with dual inhibition of EGFR as up-front treatment, but this regimen was associated with greater toxicity. The combination was not effective in reversing acquired resistance after development of a second-site acquired EGFR alteration. Our study highlights the need to develop better strategies to address on-target resistance in patients with EGFR-mutant lung cancers.

Published
2023

10. Randomized Phase II Trial of Proton Craniospinal Irradiation Versus Photon Involved-Field Radiotherapy for Patients With Solid Tumor Leptomeningeal Metastasis

Author

Jonathan T. Yang, N. Ari Wijetunga, Elena Pentsova, Suzanne Wolden, Robert J. Young, Denise Correa, Zhigang Zhang, Junting Zheng, Alexa Steckler, Weronika Bucwinska, Ashley Bernstein, Allison Betof Warner, Helena Yu, Mark G. Kris, Andrew D. Seidman, Jessica A. Wilcox, Rachna Malani, Andrew Lin, Lisa M. DeAngelis, Nancy Y. Lee, Simon N. Powell, and Adrienne Boire

Subjects
Cancer Research, Lung Neoplasms, Craniospinal Irradiation, Oncology, Carcinoma, Non-Small-Cell Lung, Antineoplastic Combined Chemotherapy Protocols, Proton Therapy, Humans, Protons, Meningeal Carcinomatosis
Abstract

PURPOSE Photon involved-field radiotherapy (IFRT) is the standard-of-care radiotherapy for patients with leptomeningeal metastasis (LM) from solid tumors. We tested whether proton craniospinal irradiation (pCSI) encompassing the entire CNS would result in superior CNS progression-free survival (PFS) compared with IFRT. PATIENTS AND METHODS We conducted a randomized, phase II trial of pCSI versus IFRT in patients with non–small-cell lung cancer and breast cancers with LM. We enrolled patients with other solid tumors to an exploratory pCSI group. For the randomized groups, patients were assigned (2:1), stratified by histology and systemic disease status, to pCSI or IFRT. The primary end point was CNS PFS. Secondary end points included overall survival (OS) and treatment-related adverse events (TAEs). RESULTS Between April 16, 2020, and October 11, 2021, 42 and 21 patients were randomly assigned to pCSI and IFRT, respectively. At planned interim analysis, a significant benefit in CNS PFS was observed with pCSI (median 7.5 months; 95% CI, 6.6 months to not reached) compared with IFRT (2.3 months; 95% CI, 1.2 to 5.8 months; P < .001). We also observed OS benefit with pCSI (9.9 months; 95% CI, 7.5 months to not reached) versus IFRT (6.0 months; 95% CI, 3.9 months to not reached; P = .029). There was no difference in the rate of grade 3 and 4 TAEs ( P = .19). In the exploratory pCSI group, 35 patients enrolled, the median CNS PFS was 5.8 months (95% CI, 4.4 to 9.1 months) and OS was 6.6 months (95% CI, 5.4 to 11 months). CONCLUSION Compared with photon IFRT, we found pCSI improved CNS PFS and OS for patients with non–small-cell lung cancer and breast cancer with LM with no increase in serious TAEs.

Published
2022

11. Supplemental Figure 1 from Brief Report: Combination of Osimertinib and Dacomitinib to Mitigate Primary and Acquired Resistance in EGFR-Mutant Lung Adenocarcinomas

Author

Helena A. Yu, Franziska Michor, Gregory J. Riely, Mark G. Kris, Marc Ladanyi, Paul K. Paik, Andrew J. Plodkowski, Sara A. Hayes, Afsheen N. Iqbal, Isabel R. Preeshagul, Linda S. Ahn, Khadeja A. Moses, Alex Makhnin, and Arielle Elkrief

Abstract

Supplemental Figure 1. Dose modifications of Combination Osimertinib and Dacomitinib (initial therapy study).

Published
2023

12. Supplemental Figure 4 from Brief Report: Combination of Osimertinib and Dacomitinib to Mitigate Primary and Acquired Resistance in EGFR-Mutant Lung Adenocarcinomas

Author

Helena A. Yu, Franziska Michor, Gregory J. Riely, Mark G. Kris, Marc Ladanyi, Paul K. Paik, Andrew J. Plodkowski, Sara A. Hayes, Afsheen N. Iqbal, Isabel R. Preeshagul, Linda S. Ahn, Khadeja A. Moses, Alex Makhnin, and Arielle Elkrief

Abstract

Supplemental Figure 4. A. Median progression-free survival and B. Overall survival for patients enrolled in the acquired resistance study

Published
2023

13. Data from Targeting S100A9–ALDH1A1–Retinoic Acid Signaling to Suppress Brain Relapse in EGFR-Mutant Lung Cancer

Author

Swarnali Acharyya, Joan Massague, Mark G. Kris, Catherine A. Shu, Anjali Saqi, Paul K. Paik, Helena A. Yu, Peter Canoll, Cathy Mendelsohn, Adolfo A. Ferrando, Elisa de Stanchina, Katia Manova-Todorova, Angeliki Mela, Galina G. Lagos, Hanna Scholze, Timothy James Zhong, Ahmad Rushdi Shakri, S. Aidan Quinn, Courtney Coker, Wanchao Ma, Yifan Tai, Seoyoung Han, and Anup Kumar Biswas

Abstract

The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib has significantly prolonged progression-free survival (PFS) in patients with EGFR-mutant lung cancer, including those with brain metastases. However, despite striking initial responses, osimertinib-treated patients eventually develop lethal metastatic relapse, often to the brain. Although osimertinib-refractory brain relapse is a major clinical challenge, its underlying mechanisms remain poorly understood. Using metastatic models of EGFR-mutant lung cancer, we show that cancer cells expressing high intracellular S100A9 escape osimertinib and initiate brain relapses. Mechanistically, S100A9 upregulates ALDH1A1 expression and activates the retinoic acid (RA) signaling pathway in osimertinib-refractory cancer cells. We demonstrate that the genetic repression of S100A9, ALDH1A1, or RA receptors (RAR) in cancer cells, or treatment with a pan-RAR antagonist, dramatically reduces brain metastasis. Importantly, S100A9 expression in cancer cells correlates with poor PFS in osimertinib-treated patients. Our study, therefore, identifies a novel, therapeutically targetable S100A9–ALDH1A1–RA axis that drives brain relapse.Significance:Treatment with the EGFR TKI osimertinib prolongs the survival of patients with EGFR-mutant lung cancer; however, patients develop metastatic relapses, often to the brain. We identified a novel intracellular S100A9–ALDH1A1–RA signaling pathway that drives lethal brain relapse and can be targeted by pan-RAR antagonists to prevent cancer progression and prolong patient survival.This article is highlighted in the In This Issue feature, p. 873

Published
2023

14. Supplementary Figure from Targeting S100A9–ALDH1A1–Retinoic Acid Signaling to Suppress Brain Relapse in EGFR-Mutant Lung Cancer

Author

Swarnali Acharyya, Joan Massague, Mark G. Kris, Catherine A. Shu, Anjali Saqi, Paul K. Paik, Helena A. Yu, Peter Canoll, Cathy Mendelsohn, Adolfo A. Ferrando, Elisa de Stanchina, Katia Manova-Todorova, Angeliki Mela, Galina G. Lagos, Hanna Scholze, Timothy James Zhong, Ahmad Rushdi Shakri, S. Aidan Quinn, Courtney Coker, Wanchao Ma, Yifan Tai, Seoyoung Han, and Anup Kumar Biswas

Abstract

Supplementary Figure from Targeting S100A9–ALDH1A1–Retinoic Acid Signaling to Suppress Brain Relapse in EGFR-Mutant Lung Cancer

Published
2023

15. Data from Response to ERBB3-Directed Targeted Therapy in NRG1-Rearranged Cancers

Author

Gopinath Ganji, Marc Ladanyi, Natasha Rekhtman, Ryma Benayed, Christopher Matheny, Maria E. Arcila, Mark G. Kris, Charles M. Rudin, Gregory J. Riely, Victor Martinez, William W. Lockwood, Huichun Tai, Jason Chang, Joseph Montecalvo, Kenneth Ng, Joshua Sabari, Andrew J. Plodkowski, Morana Vojnic, Lukas Delasos, Roger S. Smith, Anja Ruusulehto, Patrice Desmeules, Henrik Edgren, Biju P. Mangatt, Romel Somwar, and Alexander Drilon

Abstract

NRG1 rearrangements are oncogenic drivers that are enriched in invasive mucinous adenocarcinomas (IMA) of the lung. The oncoprotein binds ERBB3–ERBB2 heterodimers and activates downstream signaling, supporting a therapeutic paradigm of ERBB3/ERBB2 inhibition. As proof of concept, a durable response was achieved with anti-ERBB3 mAb therapy (GSK2849330) in an exceptional responder with an NRG1-rearranged IMA on a phase I trial (NCT01966445). In contrast, response was not achieved with anti-ERBB2 therapy (afatinib) in four patients with NRG1-rearranged IMA (including the index patient post-GSK2849330). Although in vitro data supported the use of either ERBB3 or ERBB2 inhibition, these clinical results were consistent with more profound antitumor activity and downstream signaling inhibition with anti-ERBB3 versus anti-ERBB2 therapy in an NRG1-rearranged patient-derived xenograft model. Analysis of 8,984 and 17,485 tumors in The Cancer Genome Atlas and MSK-IMPACT datasets, respectively, identified NRG1 rearrangements with novel fusion partners in multiple histologies, including breast, head and neck, renal, lung, ovarian, pancreatic, prostate, and uterine cancers.Significance: This series highlights the utility of ERBB3 inhibition as a novel treatment paradigm for NRG1-rearranged cancers. In addition, it provides preliminary evidence that ERBB3 inhibition may be more optimal than ERBB2 inhibition. The identification of NRG1 rearrangements across various solid tumors supports a basket trial approach to drug development. Cancer Discov; 8(6); 686–95. ©2018 AACR.See related commentary by Wilson and Politi, p. 676.This article is highlighted in the In This Issue feature, p. 663

Published
2023

16. Supplementary Figure Legends 1-5 from HER2 Amplification: A Potential Mechanism of Acquired Resistance to EGFR Inhibition in EGFR-Mutant Lung Cancers That Lack the Second-Site EGFRT790M Mutation

Author

William Pao, Katerina Politi, Marc Ladanyi, Vincent A. Miller, Mark G. Kris, Greg J. Riely, Mary Ann Melnick, Paula J. Spitzler, Yelena Y. Janjigian, Kadoaki Ohashi, Elisa de Stanchina, Xiaoling Song, Caroline A. Nebhan, Maria E. Arcila, Valentina Pirazzoli, and Ken Takezawa

Abstract

PDF file - 29K

Published
2023

17. Supplementary Figure 4 from Prospective Comprehensive Molecular Characterization of Lung Adenocarcinomas for Efficient Patient Matching to Approved and Emerging Therapies

Author

Gregory J. Riely, Marc Ladanyi, David B. Solit, Michael F. Berger, David M. Hyman, Charles M. Rudin, Nikolaus Schultz, Barry S. Taylor, José Baselga, Jamie E. Chaft, Mark G. Kris, Valerie W. Rusch, Ryma Benayed, Dalicia N. Reales, Matthew D. Hellmann, Alexander Drilon, Paul K. Paik, Helena A. Yu, Bob T. Li, Michelle S. Ginsberg, Natasha Rekhtman, Ahmet Zehir, Aphrothiti J. Hanrahan, Hannah C. Johnsen, Sizhi Paul Gao, Gowtham Jayakumaran, Philip Jonsson, Ritika Kundra, Andy Ni, Matthew T. Chang, JianJiong Gao, Debyani Chakravarty, David Barron, Maria E. Arcila, Hyunjae R. Kim, and Emmet J. Jordan

Abstract

Breakdown of RET and ROS1 fusion positive patients

Published
2023

19. Supplementary Fig 3 from HER2-Mediated Internalization of Cytotoxic Agents in ERBB2 Amplified or Mutant Lung Cancers

Author

Maurizio Scaltriti, Charles M. Rudin, Neal Rosen, Elisa de Stanchina, Gary A. Ulaner, Junji Tsurutani, Ronglai Shen, John T. Poirier, Mark G. Kris, Maria E. Arcila, Pedram Razavi, Jorge S. Reis-Filho, Vicky Makker, Alan L. Ho, Darren J. Buonocore, Jason S. Lewis, David M. Hyman, Fabiola Cecchi, Anuja Bhalkikar, Wei-Li Liao, Sheeno Thyparambil, Helena A. Yu, David R. Jones, James M. Isbell, Michael Offin, Tony Ng, Paul R. Barber, Michael F. Berger, David B. Solit, Nancy U. Lin, Rachel A. Freedman, Irmina Diala, Alshad S. Lalani, Clare J. Wilhem, Gregory Weitsman, Besnik Qeriqi, Megan Little, Inna Khodos, Marissa Mattar, Chongrui Xu, Mackenzie L. Myers, Hai-Yan Tu, Sophie Shifman, Yanyan Cai, Laura Baldino, Emiliano Cocco, Sandra Misale, Flavia Michelini, and Bob T. Li

Abstract

Supplementary Fig 3

Published
2023

20. Supplementary Figure 1 from Prospective Comprehensive Molecular Characterization of Lung Adenocarcinomas for Efficient Patient Matching to Approved and Emerging Therapies

Author

Gregory J. Riely, Marc Ladanyi, David B. Solit, Michael F. Berger, David M. Hyman, Charles M. Rudin, Nikolaus Schultz, Barry S. Taylor, José Baselga, Jamie E. Chaft, Mark G. Kris, Valerie W. Rusch, Ryma Benayed, Dalicia N. Reales, Matthew D. Hellmann, Alexander Drilon, Paul K. Paik, Helena A. Yu, Bob T. Li, Michelle S. Ginsberg, Natasha Rekhtman, Ahmet Zehir, Aphrothiti J. Hanrahan, Hannah C. Johnsen, Sizhi Paul Gao, Gowtham Jayakumaran, Philip Jonsson, Ritika Kundra, Andy Ni, Matthew T. Chang, JianJiong Gao, Debyani Chakravarty, David Barron, Maria E. Arcila, Hyunjae R. Kim, and Emmet J. Jordan

Abstract

Co-occurring Level 1-3 alterations by MSK-IMPACT in 52 patients

Published
2023

21. Data from Next-Generation Sequencing of Stage IV Squamous Cell Lung Cancers Reveals an Association of PI3K Aberrations and Evidence of Clonal Heterogeneity in Patients with Brain Metastases

Author

Mark G. Kris, Michael F. Berger, Marc Ladanyi, Venkatraman Seshan, Arshi Arora, Camelia S. Sima, Lu Wang, Natasha Rekhtman, Helen Won, Ronglai Shen, and Paul K. Paik

Abstract

Large-scale genomic characterization of squamous cell lung cancers (SQCLC) has revealed several putative oncogenic drivers. There are, however, little data to suggest that these alterations have clinical relevance. We performed comprehensive genomic profiling (including next-generation sequencing) of 79 stage IV SQCLCs and analyzed differences in the clinical characteristics of two major SQCLC subtypes: FGFR1 amplified and PI3K aberrant. Patients with PI3K-aberrant tumors had aggressive disease marked by worse survival (median overall survival, 8.6 vs. 19.1 months, P < 0.001), higher metastatic burden (>3 organs, 18% vs. 3%, P = 0.025), and greater incidence of brain metastases (27% vs. 0% in others, P < 0.001). We performed whole-exome and RNA sequencing on paired brain metastases and primary lung cancers to elucidate the metastatic process to brain. SQCLC primaries that gave rise to brain metastases exhibited truncal PTEN loss. SQCLC brain metastases exhibited a high degree of genetic heterogeneity and evidence of clonal differences between their primary sites.Significance: We performed next-generation sequencing of metastatic SQCLCs and primary lung–brain metastasis pairs, identifying PI3K-aberrant tumors as an aggressive subset associated with brain metastases. We identified genetic heterogeneity between lung primaries–brain metastases as well as clonal populations that may highlight alterations important in the metastatic process. Cancer Discov; 5(6); 610–21. ©2015 AACR.This article is highlighted in the In This Issue feature, p. 565

Published
2023

22. Supplementary Figure 5 from HER2 Amplification: A Potential Mechanism of Acquired Resistance to EGFR Inhibition in EGFR-Mutant Lung Cancers That Lack the Second-Site EGFRT790M Mutation

Author

William Pao, Katerina Politi, Marc Ladanyi, Vincent A. Miller, Mark G. Kris, Greg J. Riely, Mary Ann Melnick, Paula J. Spitzler, Yelena Y. Janjigian, Kadoaki Ohashi, Elisa de Stanchina, Xiaoling Song, Caroline A. Nebhan, Maria E. Arcila, Valentina Pirazzoli, and Ken Takezawa

Abstract

PDF file - 92K, Effects of HER2 overexpression on the sensitivity of HCC827 cells to EGFR TKIs

Published
2023

23. Supplementary Figure 4 from HER2 Amplification: A Potential Mechanism of Acquired Resistance to EGFR Inhibition in EGFR-Mutant Lung Cancers That Lack the Second-Site EGFRT790M Mutation

Author

William Pao, Katerina Politi, Marc Ladanyi, Vincent A. Miller, Mark G. Kris, Greg J. Riely, Mary Ann Melnick, Paula J. Spitzler, Yelena Y. Janjigian, Kadoaki Ohashi, Elisa de Stanchina, Xiaoling Song, Caroline A. Nebhan, Maria E. Arcila, Valentina Pirazzoli, and Ken Takezawa

Abstract

PDF file - 91K, Levels of HER2 affect the sensitivity of EGFR-mutant NSCLC cells to EGFR TKIs

Published
2023

24. Supplementary Tables 2 - 6 from Next-Generation Sequencing of Stage IV Squamous Cell Lung Cancers Reveals an Association of PI3K Aberrations and Evidence of Clonal Heterogeneity in Patients with Brain Metastases

Author

Mark G. Kris, Michael F. Berger, Marc Ladanyi, Venkatraman Seshan, Arshi Arora, Camelia S. Sima, Lu Wang, Natasha Rekhtman, Helen Won, Ronglai Shen, and Paul K. Paik

Abstract

Supplementary Table 2. Frequency of selected genes in SQ-MAP vs. TCGA. Supplementary Table 3. Clinical characteristics of patients with resected brain metastases. Supplementary Table 4. Genes exhibiting clonal evolution from primary lung tumors and matched brain metastases. Data from PP1 and PP4 are shown. Supplementary Table 5. List of 279 oncogenes and tumor suppressors covered by the Integrated Mutation Profiling of Actionable Cancer Targets (IMPACT) assay. Supplementary Table 6. Computational estimates of tumor purity (fractional) from whole-exome sequencing data for the paired lung primary and brain metastasis tumor samples compared to pathological evaluation of tumor purity in the same samples.

Published
2023

25. Supplementary Table 1 from Next-Generation Sequencing of Stage IV Squamous Cell Lung Cancers Reveals an Association of PI3K Aberrations and Evidence of Clonal Heterogeneity in Patients with Brain Metastases

Author

Mark G. Kris, Michael F. Berger, Marc Ladanyi, Venkatraman Seshan, Arshi Arora, Camelia S. Sima, Lu Wang, Natasha Rekhtman, Helen Won, Ronglai Shen, and Paul K. Paik

Abstract

Supplementary Table 1. Complete list of somatic mutations and copy number alterations detected by IMPACT in 79 stage IV SQCLC patients with clinical annotation.

Published
2023

26. Supplementary Fig 2 from HER2-Mediated Internalization of Cytotoxic Agents in ERBB2 Amplified or Mutant Lung Cancers

Author

Maurizio Scaltriti, Charles M. Rudin, Neal Rosen, Elisa de Stanchina, Gary A. Ulaner, Junji Tsurutani, Ronglai Shen, John T. Poirier, Mark G. Kris, Maria E. Arcila, Pedram Razavi, Jorge S. Reis-Filho, Vicky Makker, Alan L. Ho, Darren J. Buonocore, Jason S. Lewis, David M. Hyman, Fabiola Cecchi, Anuja Bhalkikar, Wei-Li Liao, Sheeno Thyparambil, Helena A. Yu, David R. Jones, James M. Isbell, Michael Offin, Tony Ng, Paul R. Barber, Michael F. Berger, David B. Solit, Nancy U. Lin, Rachel A. Freedman, Irmina Diala, Alshad S. Lalani, Clare J. Wilhem, Gregory Weitsman, Besnik Qeriqi, Megan Little, Inna Khodos, Marissa Mattar, Chongrui Xu, Mackenzie L. Myers, Hai-Yan Tu, Sophie Shifman, Yanyan Cai, Laura Baldino, Emiliano Cocco, Sandra Misale, Flavia Michelini, and Bob T. Li

Abstract

Supplementary Fig 2

Published
2023

27. Supplementary Table from Response to ERBB3-Directed Targeted Therapy in NRG1-Rearranged Cancers

Author

Gopinath Ganji, Marc Ladanyi, Natasha Rekhtman, Ryma Benayed, Christopher Matheny, Maria E. Arcila, Mark G. Kris, Charles M. Rudin, Gregory J. Riely, Victor Martinez, William W. Lockwood, Huichun Tai, Jason Chang, Joseph Montecalvo, Kenneth Ng, Joshua Sabari, Andrew J. Plodkowski, Morana Vojnic, Lukas Delasos, Roger S. Smith, Anja Ruusulehto, Patrice Desmeules, Henrik Edgren, Biju P. Mangatt, Romel Somwar, and Alexander Drilon

Abstract

Table S1

Published
2023

28. Supplementary Figure 6 from Prospective Comprehensive Molecular Characterization of Lung Adenocarcinomas for Efficient Patient Matching to Approved and Emerging Therapies

Author

Gregory J. Riely, Marc Ladanyi, David B. Solit, Michael F. Berger, David M. Hyman, Charles M. Rudin, Nikolaus Schultz, Barry S. Taylor, José Baselga, Jamie E. Chaft, Mark G. Kris, Valerie W. Rusch, Ryma Benayed, Dalicia N. Reales, Matthew D. Hellmann, Alexander Drilon, Paul K. Paik, Helena A. Yu, Bob T. Li, Michelle S. Ginsberg, Natasha Rekhtman, Ahmet Zehir, Aphrothiti J. Hanrahan, Hannah C. Johnsen, Sizhi Paul Gao, Gowtham Jayakumaran, Philip Jonsson, Ritika Kundra, Andy Ni, Matthew T. Chang, JianJiong Gao, Debyani Chakravarty, David Barron, Maria E. Arcila, Hyunjae R. Kim, and Emmet J. Jordan

Abstract

Types of Clinical trials patients enrolled to according to level 1-4 and UMD assigned samples

Published
2023

29. Supplementary tables S1-4 from Prospective Comprehensive Molecular Characterization of Lung Adenocarcinomas for Efficient Patient Matching to Approved and Emerging Therapies

Author

Gregory J. Riely, Marc Ladanyi, David B. Solit, Michael F. Berger, David M. Hyman, Charles M. Rudin, Nikolaus Schultz, Barry S. Taylor, José Baselga, Jamie E. Chaft, Mark G. Kris, Valerie W. Rusch, Ryma Benayed, Dalicia N. Reales, Matthew D. Hellmann, Alexander Drilon, Paul K. Paik, Helena A. Yu, Bob T. Li, Michelle S. Ginsberg, Natasha Rekhtman, Ahmet Zehir, Aphrothiti J. Hanrahan, Hannah C. Johnsen, Sizhi Paul Gao, Gowtham Jayakumaran, Philip Jonsson, Ritika Kundra, Andy Ni, Matthew T. Chang, JianJiong Gao, Debyani Chakravarty, David Barron, Maria E. Arcila, Hyunjae R. Kim, and Emmet J. Jordan

Abstract

Supplementary Table S1: List of actionable genes and potential matched therapy Supplementary Table S2: List of co-occurring Level 1-4 mutations Supplementary Table S3: EGFR mutations identified and associated therapy Supplementary Table S4: List of 410 genes in MSK-IMPACT assay

Published
2023

33. Supplementary Figures from Response to ERBB3-Directed Targeted Therapy in NRG1-Rearranged Cancers

Author

Gopinath Ganji, Marc Ladanyi, Natasha Rekhtman, Ryma Benayed, Christopher Matheny, Maria E. Arcila, Mark G. Kris, Charles M. Rudin, Gregory J. Riely, Victor Martinez, William W. Lockwood, Huichun Tai, Jason Chang, Joseph Montecalvo, Kenneth Ng, Joshua Sabari, Andrew J. Plodkowski, Morana Vojnic, Lukas Delasos, Roger S. Smith, Anja Ruusulehto, Patrice Desmeules, Henrik Edgren, Biju P. Mangatt, Romel Somwar, and Alexander Drilon

Abstract

Figures S1, S2, S3, S4, and S5

Published
2023

34. Data from HER2-Mediated Internalization of Cytotoxic Agents in ERBB2 Amplified or Mutant Lung Cancers

Author

Maurizio Scaltriti, Charles M. Rudin, Neal Rosen, Elisa de Stanchina, Gary A. Ulaner, Junji Tsurutani, Ronglai Shen, John T. Poirier, Mark G. Kris, Maria E. Arcila, Pedram Razavi, Jorge S. Reis-Filho, Vicky Makker, Alan L. Ho, Darren J. Buonocore, Jason S. Lewis, David M. Hyman, Fabiola Cecchi, Anuja Bhalkikar, Wei-Li Liao, Sheeno Thyparambil, Helena A. Yu, David R. Jones, James M. Isbell, Michael Offin, Tony Ng, Paul R. Barber, Michael F. Berger, David B. Solit, Nancy U. Lin, Rachel A. Freedman, Irmina Diala, Alshad S. Lalani, Clare J. Wilhem, Gregory Weitsman, Besnik Qeriqi, Megan Little, Inna Khodos, Marissa Mattar, Chongrui Xu, Mackenzie L. Myers, Hai-Yan Tu, Sophie Shifman, Yanyan Cai, Laura Baldino, Emiliano Cocco, Sandra Misale, Flavia Michelini, and Bob T. Li

Abstract

Amplification of and oncogenic mutations in ERBB2, the gene encoding the HER2 receptor tyrosine kinase, promote receptor hyperactivation and tumor growth. Here we demonstrate that HER2 ubiquitination and internalization, rather than its overexpression, are key mechanisms underlying endocytosis and consequent efficacy of the anti-HER2 antibody–drug conjugates (ADC) ado-trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd) in lung cancer cell lines and patient-derived xenograft models. These data translated into a 51% response rate in a clinical trial of T-DM1 in 49 patients with ERBB2-amplified or -mutant lung cancers. We show that cotreatment with irreversible pan-HER inhibitors enhances receptor ubiquitination and consequent ADC internalization and efficacy. We also demonstrate that ADC switching to T-DXd, which harbors a different cytotoxic payload, achieves durable responses in a patient with lung cancer and corresponding xenograft model developing resistance to T-DM1. Our findings may help guide future clinical trials and expand the field of ADC as cancer therapy.Significance:T-DM1 is clinically effective in lung cancers with amplification of or mutations in ERBB2. This activity is enhanced by cotreatment with irreversible pan-HER inhibitors, or ADC switching to T-DXd. These results may help address unmet needs of patients with HER2-activated tumors and no approved targeted therapy.See related commentary by Rolfo and Russo, p. 643.This article is highlighted in the In This Issue feature, p. 627

Published
2023

35. Supplemental Table 1 from Safety and Efficacy of Re-treating with Immunotherapy after Immune-Related Adverse Events in Patients with NSCLC

Author

Matthew D. Hellmann, Jamie E. Chaft, Charles M. Rudin, Mark G. Kris, Niamh M. Long, Darragh F. Halpenny, Elizabeth Panora, Olivia Wilkins, Maya Gambarin-Gelwan, Mario E. Lacouture, Andy Ni, Andrew J. Plodkowski, Hira Rizvi, and Fernando C. Santini

Abstract

Patients with Advanced NSCLC Treated at MSKCC with Immunotherapy From April 2011 to May 2016

Published
2023

36. Supplementary Fig 5 from HER2-Mediated Internalization of Cytotoxic Agents in ERBB2 Amplified or Mutant Lung Cancers

Author

Maurizio Scaltriti, Charles M. Rudin, Neal Rosen, Elisa de Stanchina, Gary A. Ulaner, Junji Tsurutani, Ronglai Shen, John T. Poirier, Mark G. Kris, Maria E. Arcila, Pedram Razavi, Jorge S. Reis-Filho, Vicky Makker, Alan L. Ho, Darren J. Buonocore, Jason S. Lewis, David M. Hyman, Fabiola Cecchi, Anuja Bhalkikar, Wei-Li Liao, Sheeno Thyparambil, Helena A. Yu, David R. Jones, James M. Isbell, Michael Offin, Tony Ng, Paul R. Barber, Michael F. Berger, David B. Solit, Nancy U. Lin, Rachel A. Freedman, Irmina Diala, Alshad S. Lalani, Clare J. Wilhem, Gregory Weitsman, Besnik Qeriqi, Megan Little, Inna Khodos, Marissa Mattar, Chongrui Xu, Mackenzie L. Myers, Hai-Yan Tu, Sophie Shifman, Yanyan Cai, Laura Baldino, Emiliano Cocco, Sandra Misale, Flavia Michelini, and Bob T. Li

Abstract

Supplementary Fig 5

Published
2023

37. Supplementary Figures 1 - 6, Table 1 from EGFR Kinase Domain Duplication (EGFR-KDD) Is a Novel Oncogenic Driver in Lung Cancer That Is Clinically Responsive to Afatinib

Author

Christine M. Lovly, Jens Meiler, Siraj M. Ali, Vincent A. Miller, Marc Ladanyi, Jennifer A. Pietenpol, Mark G. Kris, Sally J. York, Monica Red Brewer, Raghu Chandramohan, Doron Lipson, Mark Bailey, Timothy M. Shaver, Jonathan H. Sheehan, and Jean-Nicolas Gallant

Abstract

This document contains Supplementary Figures 1-6 and Supplementary Table 1. Supplementary Figure 1. Sequencing reads of EGFR-KDD in index patient with lung adenocarcinoma. Supplementary Figure 2. cDNA sequence of EGFR-KDD. Supplementary Figure 3. Sequencing reads identifying EGFR-KDD in a lung adenocarcinoma tumor from The Cancer Genome Atlas. Supplementary Figure 4. Autophosphorylation of endogenous EGFR-KDD in A1235 cells. Supplementary Figure 5. Colony formation of NR6 cells expressing EGFR variants. Supplementary Figure 6. Efficacy of EGFR TKIs in endogenous and ectopic models of the EGFR-KDD. Supplementary Table 1. Results of MTT curve fitting from Prism.

Published
2023

38. Supplementary Figure 5 from Prospective Comprehensive Molecular Characterization of Lung Adenocarcinomas for Efficient Patient Matching to Approved and Emerging Therapies

Author

Gregory J. Riely, Marc Ladanyi, David B. Solit, Michael F. Berger, David M. Hyman, Charles M. Rudin, Nikolaus Schultz, Barry S. Taylor, José Baselga, Jamie E. Chaft, Mark G. Kris, Valerie W. Rusch, Ryma Benayed, Dalicia N. Reales, Matthew D. Hellmann, Alexander Drilon, Paul K. Paik, Helena A. Yu, Bob T. Li, Michelle S. Ginsberg, Natasha Rekhtman, Ahmet Zehir, Aphrothiti J. Hanrahan, Hannah C. Johnsen, Sizhi Paul Gao, Gowtham Jayakumaran, Philip Jonsson, Ritika Kundra, Andy Ni, Matthew T. Chang, JianJiong Gao, Debyani Chakravarty, David Barron, Maria E. Arcila, Hyunjae R. Kim, and Emmet J. Jordan

Abstract

Breakdown of MAP2K1, RAF1, ARAF, FGFR3-TACC3 fusion and CDKN2A loss patients

Published
2023

39. Supplemental Table 3 from Safety and Efficacy of Re-treating with Immunotherapy after Immune-Related Adverse Events in Patients with NSCLC

Author

Matthew D. Hellmann, Jamie E. Chaft, Charles M. Rudin, Mark G. Kris, Niamh M. Long, Darragh F. Halpenny, Elizabeth Panora, Olivia Wilkins, Maya Gambarin-Gelwan, Mario E. Lacouture, Andy Ni, Andrew J. Plodkowski, Hira Rizvi, and Fernando C. Santini

Abstract

Retreatment Cohort - Recurrent irAEs: Characteristics of The Recurrent Immune-Related Toxicity

Published
2023

40. Supplementary Methods, Figure Legends, Table Legend from EGFR Kinase Domain Duplication (EGFR-KDD) Is a Novel Oncogenic Driver in Lung Cancer That Is Clinically Responsive to Afatinib

Author

Christine M. Lovly, Jens Meiler, Siraj M. Ali, Vincent A. Miller, Marc Ladanyi, Jennifer A. Pietenpol, Mark G. Kris, Sally J. York, Monica Red Brewer, Raghu Chandramohan, Doron Lipson, Mark Bailey, Timothy M. Shaver, Jonathan H. Sheehan, and Jean-Nicolas Gallant

Abstract

This document contains Supplementary Methods, Supplementary Figure Legends, and Supplementary Table Legend.

Published
2023

43. Supplementary Figure 2 from Prospective Comprehensive Molecular Characterization of Lung Adenocarcinomas for Efficient Patient Matching to Approved and Emerging Therapies

Author

Gregory J. Riely, Marc Ladanyi, David B. Solit, Michael F. Berger, David M. Hyman, Charles M. Rudin, Nikolaus Schultz, Barry S. Taylor, José Baselga, Jamie E. Chaft, Mark G. Kris, Valerie W. Rusch, Ryma Benayed, Dalicia N. Reales, Matthew D. Hellmann, Alexander Drilon, Paul K. Paik, Helena A. Yu, Bob T. Li, Michelle S. Ginsberg, Natasha Rekhtman, Ahmet Zehir, Aphrothiti J. Hanrahan, Hannah C. Johnsen, Sizhi Paul Gao, Gowtham Jayakumaran, Philip Jonsson, Ritika Kundra, Andy Ni, Matthew T. Chang, JianJiong Gao, Debyani Chakravarty, David Barron, Maria E. Arcila, Hyunjae R. Kim, and Emmet J. Jordan

Abstract

Patient 1 Concurrent EGFR and KRAS mutations in a patient identified by MSK-IMPACT

Published
2023

44. Supplementary Figure 7 from Prospective Comprehensive Molecular Characterization of Lung Adenocarcinomas for Efficient Patient Matching to Approved and Emerging Therapies

Author

Gregory J. Riely, Marc Ladanyi, David B. Solit, Michael F. Berger, David M. Hyman, Charles M. Rudin, Nikolaus Schultz, Barry S. Taylor, José Baselga, Jamie E. Chaft, Mark G. Kris, Valerie W. Rusch, Ryma Benayed, Dalicia N. Reales, Matthew D. Hellmann, Alexander Drilon, Paul K. Paik, Helena A. Yu, Bob T. Li, Michelle S. Ginsberg, Natasha Rekhtman, Ahmet Zehir, Aphrothiti J. Hanrahan, Hannah C. Johnsen, Sizhi Paul Gao, Gowtham Jayakumaran, Philip Jonsson, Ritika Kundra, Andy Ni, Matthew T. Chang, JianJiong Gao, Debyani Chakravarty, David Barron, Maria E. Arcila, Hyunjae R. Kim, and Emmet J. Jordan

Abstract

Median number of mutations in samples sequenced by MSK-IMPACT in patients with a Level 1-4 alteration or assigned to the unknown mitogenic driver cohort.

Published
2023

45. Supplementary Methods from Response to ERBB3-Directed Targeted Therapy in NRG1-Rearranged Cancers

Author

Gopinath Ganji, Marc Ladanyi, Natasha Rekhtman, Ryma Benayed, Christopher Matheny, Maria E. Arcila, Mark G. Kris, Charles M. Rudin, Gregory J. Riely, Victor Martinez, William W. Lockwood, Huichun Tai, Jason Chang, Joseph Montecalvo, Kenneth Ng, Joshua Sabari, Andrew J. Plodkowski, Morana Vojnic, Lukas Delasos, Roger S. Smith, Anja Ruusulehto, Patrice Desmeules, Henrik Edgren, Biju P. Mangatt, Romel Somwar, and Alexander Drilon

Abstract

Supplementary Methods

Published
2023

46. Supplementary Table 1 from HER2-Mediated Internalization of Cytotoxic Agents in ERBB2 Amplified or Mutant Lung Cancers

Author

Maurizio Scaltriti, Charles M. Rudin, Neal Rosen, Elisa de Stanchina, Gary A. Ulaner, Junji Tsurutani, Ronglai Shen, John T. Poirier, Mark G. Kris, Maria E. Arcila, Pedram Razavi, Jorge S. Reis-Filho, Vicky Makker, Alan L. Ho, Darren J. Buonocore, Jason S. Lewis, David M. Hyman, Fabiola Cecchi, Anuja Bhalkikar, Wei-Li Liao, Sheeno Thyparambil, Helena A. Yu, David R. Jones, James M. Isbell, Michael Offin, Tony Ng, Paul R. Barber, Michael F. Berger, David B. Solit, Nancy U. Lin, Rachel A. Freedman, Irmina Diala, Alshad S. Lalani, Clare J. Wilhem, Gregory Weitsman, Besnik Qeriqi, Megan Little, Inna Khodos, Marissa Mattar, Chongrui Xu, Mackenzie L. Myers, Hai-Yan Tu, Sophie Shifman, Yanyan Cai, Laura Baldino, Emiliano Cocco, Sandra Misale, Flavia Michelini, and Bob T. Li

Abstract

Supplementary Table 1

Published
2023

48. Supplementary Figures 1 - 2 from Next-Generation Sequencing of Stage IV Squamous Cell Lung Cancers Reveals an Association of PI3K Aberrations and Evidence of Clonal Heterogeneity in Patients with Brain Metastases

Author

Mark G. Kris, Michael F. Berger, Marc Ladanyi, Venkatraman Seshan, Arshi Arora, Camelia S. Sima, Lu Wang, Natasha Rekhtman, Helen Won, Ronglai Shen, and Paul K. Paik

Abstract

Supplementary Figure 1. Copy number pattern in paired lung cancer primaries and brain metastases from patients PP1, PP2, and PP4. Red, blue, and white indicate gain, loss, neutral states, respectively. The total number of shared cytobands (percent shared) between the primary and brain metastases are indicated at the bottom. Supplementary Figure 2A. Genome-wide copy number profile of the PP1 brain metastasis (A) and lung primary (B). Total log-copy ratio (logR) in the tumor versus normal and minor allele frequency (MAF) in the tumor are plotted. Yellow line represents joint segmentation of logR and MAF. Supplementary Figure 2B. Genome-wide copy number profile of the PP4 brain metastasis (A) and lung primary (B). Supplementary Figure 2C. Genome-wide copy number profile of the PP2 brain metastasis (A) and lung primary (B). Pooled normal was used to generate the logR plot. Supplementary Figure 2D. Genome-wide copy number profile of the PP3 brain metastasis (A) and PP5 brain metastasis (B).

Published
2023

50. Supplementary Fig 6 from HER2-Mediated Internalization of Cytotoxic Agents in ERBB2 Amplified or Mutant Lung Cancers

Author

Maurizio Scaltriti, Charles M. Rudin, Neal Rosen, Elisa de Stanchina, Gary A. Ulaner, Junji Tsurutani, Ronglai Shen, John T. Poirier, Mark G. Kris, Maria E. Arcila, Pedram Razavi, Jorge S. Reis-Filho, Vicky Makker, Alan L. Ho, Darren J. Buonocore, Jason S. Lewis, David M. Hyman, Fabiola Cecchi, Anuja Bhalkikar, Wei-Li Liao, Sheeno Thyparambil, Helena A. Yu, David R. Jones, James M. Isbell, Michael Offin, Tony Ng, Paul R. Barber, Michael F. Berger, David B. Solit, Nancy U. Lin, Rachel A. Freedman, Irmina Diala, Alshad S. Lalani, Clare J. Wilhem, Gregory Weitsman, Besnik Qeriqi, Megan Little, Inna Khodos, Marissa Mattar, Chongrui Xu, Mackenzie L. Myers, Hai-Yan Tu, Sophie Shifman, Yanyan Cai, Laura Baldino, Emiliano Cocco, Sandra Misale, Flavia Michelini, and Bob T. Li

Abstract

Supplementary Fig 6

Published
2023

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