Case Report: Identification of Two Rare Fusions, PDK1-ALK and STRN-ALK, That Coexist in a Lung Adenocarcinoma Patient and the Response to Alectinib

Several double ALK fusions coexisting in one patient have been reported. However, few studies have reported the clinical efficacy of ALK inhibitors in rare double ALK fusions. Here, we described a rare PDK1-ALK, STRN-ALK double-fusion variant in a patient with metastatic lung adenocarcinoma. The patient responded well to alectinib (600 mg) twice daily. This case shows a promising treatment option for patients with rare ALK double-fusion variants. READ ARTICLE

Frontiers in oncology DOI:10.3389/fonc.2021.722843

Authors: Zeng H, Li Y, Wang Y, Huang M, Zhang Y, Tian P, Li W.

Cycling cancer persister cells arise from lineages with distinct programs

Non-genetic mechanisms have recently emerged as important drivers of cancer therapy failure1, where some cancer cells can enter a reversible drug-tolerant persister state in response to treatment2. Although most cancer persisters remain arrested in the presence of the drug, a rare subset can re-enter the cell cycle under constitutive drug treatment. Little is known about the non-genetic mechanisms that enable cancer persisters to maintain proliferative capacity in the presence of drugs. To study this rare, transiently resistant, proliferative persister population, we developed Watermelon, a high-complexity expressed barcode lentiviral library for simultaneous tracing of each cell’s clonal origin and proliferative and transcriptional states. Here we show that cycling and non-cycling persisters arise from different cell lineages with distinct transcriptional and metabolic programs. Upregulation of antioxidant gene programs and a metabolic shift to fatty acid oxidation are associated with..... READ ARTICLE

Nature DOI:10.1038/s41586-021-03796-6

Authors: Yaara Oren, Michael Tsabar, Michael S. Cuoco, Liat Amir-Zilberstein, Heidie F. Cabanos, Jan-Christian Hütter, Bomiao Hu, Pratiksha I. Thakore, Marcin Tabaka, Charles P. Fulco, William Colgan, Brandon M. Cuevas, Sara A. Hurvitz, Dennis J. Slamon, Amy Deik, Kerry A. Pierce, Clary Clish, Aaron N. Hata, Elma Zaganjor, Galit Lahav, Katerina Politi, Joan S. Brugge & Aviv Regev

Pre-Clinical, group3Kirk SmithAugust 11, 2021Watermelon library, lineage diversity and fate, models

ALK summit 2021: Keynote speaker, Tasneeem Ahmed talks about where the ALK space is today and the HOPE we have for the future with Q&A from the ALK Community.

Welcome to day 2 of ALK Summit 2021: STRONGER TOGETHER and keynote speaker, Tasneeem Ahmed talks about where the ALK space is today and the HOPE we have for the future with Q&A from the ALK Community. WATCH VIDEO

ALK Positive Inc.

Authors: Amanda Nerstad, Bill Westlake and Tasneem Ahmed

Video, group3Kirk SmithAugust 10, 2021ALK summit 2021

Research Funded by ALK Positive, updated on August 9, 2021

ALK Summit 2021: STRONGER TOGETHER: Research Funded by ALK Positive- Hear From the Researchers Mark Awad, Trever Bivona, Roberto Chiarle, Ibiayi Dagogo- Jack, Juston Gainor, John Iafrate, Christine Lovly, Raphael Nemenoff. Moderators: Colin Barton and Emily Venanzi WATCH VIDEO

ALK Positive Inc.

Authors: Mark Awad, Trever Bivona, Roberto Chiarle, Ibiayi Dagogo- Jack, Juston Gainor, John Iafrate, Christine Lovly and Raphael Nemenoff

Video, group3Kirk SmithAugust 9, 2021ALK summit 2021

ALK summit 2021: What is Next After Lorlatinib?

ALK Summit 2021: STRONGER TOGETHER. What is Next After Lorlatinib? 4th Generation TKI’s and Beyond Speakers: dr. Ross Camidge, MD, PHD University of Colorado Cancer Center, Dr. Christine Lovly, MD PhD, BA Vanderbilt- Ingram Cancer Center. Moderator(s): Colin Barton, Emily Vennzi. Dr. Ross Camidge and Dr. Christine Lovly speak about the many treatment options that are available NOW if a patient experiences progression on Lorlatinib. Even more exciting, they speak about what's already visible on the horizon for new treatments that could transform our future. WATCH VIDEO

ALK Positive Inc.

Authors: Dr. Ross Camidge and Dr. Christine Lovly

Video, group3Kirk SmithAugust 9, 2021ALK summit 2021

ALK summit 2021: Benefits of a Multi Disciplinary Team

ALK summit 2021: Benefits of a Multi-Disciplinary Team: Stronger Together Dr. Ross Camidge, MD, PhD University of Colorado Cancer Center, Dr. Vicent Lam, MDAssistant Professor of Oncology, Johns Hopkins University, Dr. Drew Maghanaki, MD, MPH, UCLA Department of Radiation Oncology, Dr. Brendon Stiles, MD, Professor and Chief of Thoracic Surgery Oncology Montefiore Health System, Dr. Laura Petrilo, MD, Palliative Care at Massachusetts General Hospital Moderator: Amanda Nerstad, ALK Summit Chair. WATCH VIDEO

ALK Positive Inc.

Authors: Dr. Ross Camidge, Dr. Vicent Lam, Dr. Drew Maghanaki, Dr. Brendon Stiles, Dr. Laura Petrilo and Amanda Nerstad

Video, group3Kirk SmithAugust 9, 2021ALK summit 2021

ALK Gene Rearrangements in Lung Adenocarcinomas: Concordance of Immunohistochemistry, Fluorescence In Situ Hybridization, RNA In Situ Hybridization, and RNA Next-Generation Sequencing Testing

The 2018 updated molecular testing guidelines for patients with advanced lung cancer incorporated ALK immunohistochemistry (IHC) analysis as an equivalent to fluorescence in situ hybridization (FISH) method recommended in 2013. Nevertheless, no specific recommendation for alternative methods was proposed owing to insufficient data. The aim of this study was to compare the results of ALK IHC, FISH, RNA next-generation sequencing (NGS), and RNA in situ hybridization (ISH) with available clinical data. Our results reveal high concordance among IHC, RNA NGS, and RNA ISH. In cases of discordance with available RNA NGS, FISH result was positive whereas IHC and ISH results were negative. On the basis of our data, multimodality testing is recommended to identify discrepant results and patients (un)likely to respond to tyrosine kinase inhibitors. READ ARTICLE

JTO Clinical and Research Reports DOI:0.1016/j.jtocrr.2021.100223

Authors: Carleigh R. Canterbury, Helen Fernandes, John P. Crapanzano, Vundavalli V. Murty, Mahesh M.Mansukhani, Catherine A. Shu, Matthias Szabolcs, Anjali Saqi

Comparison of solid tissue sequencing and liquid biopsy accuracy in identification of clinically relevant gene mutations and rearrangements in lung adenocarcinomas

Screening for therapeutic targets is standard of care in the management of advanced non-small cell lung cancer. However, most molecular assays utilize tumor tissue, which may not always be available. “Liquid biopsies” are plasma-based next generation sequencing (NGS) assays that use circulating tumor DNA to identify relevant targets. To compare the sensitivity, specificity, and accuracy of a plasma-based NGS assay to solid-tumor-based NGS we retrospectively analyzed sequencing results of 100 sequential patients with lung adenocarcinoma at our institution who had received concurrent testing with both a solid-tissue-based NGS assay and a commercially available plasma-based NGS assay. Patients represented both new diagnoses (79%) and disease progression on treatment (21%); the majority (83%) had stage IV disease. Tissue-NGS identified 74 clinically relevant mutations, including 52 therapeutic targets, a sensitivity of 94.8%, while plasma-NGS identified 41 clinically relevant mutations, a ..... READ ARTICLE

Modern Pathology DOI:10.1038/s41379-021-00880-0

Authors: Lawrence Hsu Lin, Douglas H. R. Allison, Yang Feng, George Jour, Kyung Park, Fang Zhou, Andre L. Moreira, Guomiao Shen, Xiaojun Feng, Joshua Sabari, Vamsidhar Velcheti, Matija Snuderl, Paolo Cotzia

Efficacy of lorlatinib in lung carcinomas carrying distinct ALK translocation variants: The results of a single-center study

Background: Lorlatinib is a novel potent ALK inhibitor, with only a few studies reporting the results of its clinical use. Methods: This study describes the outcomes of lorlatinib treatment for 35 non-small cell lung cancer patients with ALK rearrangements, who had 2 ( n = 5), 1 ( n = 26) or none ( n = 4) prior tyrosine kinase inhibitors and received lorlatinib mainly within the compassionate use program. Results: Objective tumor response (OR) and disease control (DC) were registered in 15/35 (43%) and 33/35 (94%) patients, respectively; brain metastases were particularly responsive to the treatment (OR: 22/27 (81%); DC: 27/27 (100%)). Median progression free survival (PFS) was estimated to be 21.8 months, and median overall survival (OS) approached to 70.1 months. Only 4 out of 35 patients experienced no adverse effects; two of them were the only subjects who had no clinical benefit from lorlatinib. PFS and OS in the no-adverse-events lorlatinib users were strikingly lower as compared..... READ ARTICLE

Translational Oncology DOI:10.1016/j.tranon.2021.101121

Authors: Sergey V. Orlov, Aglaya G. Iyevleva, Elena A. Filippova, Alexandra M. Lozhkina, Svetlana V. Odintsova, Tatiana N. Sokolova, Natalia V. Mitiushkina, Vladislav I. Tiurin, Elena V. Preobrazhenskaya, Alexandr A. Romanko, Alexandr S. Martianov, Alexandr O. Ivantsov, Svetlana N. Aleksakhina, Alexandr V. Togo, Evgeny N. Imyanitov.

Guidelines for clinical practice of ALK fusion detection in non-small-cell lung cancer: a proposal from the Chinese RATICAL study group

The presence of anaplastic lymphoma kinase (ALK) rearrangement defines a molecular subtype of non-small-cell lung cancer (NSCLC). ALK inhibitors (ALKIs) confer significant clinical benefits in patients with ALK-positive advanced NSCLC; therefore, it is of great clinical significance to select accurate, rapid, and appropriate ALK testing methods to screen for patients who are suitable for anti-ALK treatment. In recent years, great progress has been made in the development and clinical application of ALKIs, as well as in our understanding of acquired drug resistance mechanisms. Meanwhile, new ALK companion diagnostic platforms have been developed and applied in clinical practice. Although many studies have shown that there is a high rate of concordance among these platforms, new problems continue to appear during testing. To maximize the benefit for patients, accurate testing results can be obtained by first selecting the appropriate testing method and then formulating, optimizing, and c..... READ ARTICLE

Journal of the National Cancer Center DOI:10.1016/j.jncc.2021.07.005

Authors: Wenbin Li, Jing Zhang, Zhijie Wang, Lin Li, Jie Ma, Xiaoyang Zhou, Jie Wang, Zhiyong Liang, Jianming Ying,

Review Paper, group3Kirk SmithJuly 30, 2021ALK, Non-small-cell lung cancer, Detection method