Prof. Logan Walsh and Dr. Jonathan Spicer co-lead the 平特五不中 Lung Cancer Research Network. Their research, along with other members of the network, is an important component of the Quebec Cancer Consortium (QCC) and Marathon of Hope Cancer Centres Network (MoHCCN).
Dr. Spicer recently co-led of one of the world鈥檚 most important clinical trials of immunotherapy for lung cancer in the neoadjuvant (pre-surgery) setting. This trial recently reported in the New England Journal of Medicine that the addition of pre-surgery immunotherapy significantly improved tumour responses and controlled patients鈥� cancers for longer than standard chemotherapy alone.
Studies led by Prof. Walsh are now using GCI spatial 鈥�-omics鈥� technology to analyze samples from this and other clinical trials in lung cancer at the single-cell level. This effort includes a ground-breaking computational analysis platform featuring machine learning and computer vision approaches, developed with GCI Associate Member Prof. Kaleem Siddiqui as well as GCI members Prof. Daniela Quail, Prof. Peter Siegel, and colleagues.
Their studies are leading to new biomarkers that can predict which patients will respond to cancer therapies such as immunotherapy and develop better ways to match patients with the best therapeutic strategies.
Publication highlights:
-
Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. Forde PM, Spicer J, et al. N Engl J Med. 2022 May 26;386(21):1973-1985. doi: 10.1056/NEJMoa2202170 PMID: 35403841
-
Machine learning meets classical computer vision for accurate cell identification. Karimi et al., BioRxiv. doi:
听
Prof. Spicer, along with Profs. Daniela Quail, Logan Walsh, and Lorenzo Ferri, have been instrumental in revealing the importance of neutrophils, a cell type of the innate immune system, in lung and other cancers. Their work has helped to establish that neutrophil extracellular traps (NETs), DNA- and protein-based structures released by activated neutrophils, mediate metastatic progression, including lung cancer metastasis.
Publication highlights:
- Neutrophil extracellular traps sequester circulating tumor cells via 尾1-integrin mediated interactions. Najmeh et al. Int J Cancer. 2017 May 15;140(10):2321-2330. doi: 10.1002/ijc.30635. PMID: 28177522
- Primary tumors induce neutrophil extracellular traps with targetable metastasis promoting effects. Rayes et al. JCI Insight. 2019 Jul 25;5(16):e128008. doi: 10.1172/jci.insight.128008. PMID: 31343990
- Neutrophil oxidative stress mediates obesity-associated vascular dysfunction and metastatic transmigration. McDowell et al. Nat Cancer. 2021 May;2(5):545-562. doi: 10.1038/s43018-021-00194-9. PMID: 35122017
听
Prof. Sidong Huang has conducted a series of innovative studies on lung cancer using techniques known as 鈥渇unctional genomics鈥� 鈥� systematically inactivating each individual gene in the genomes of lung cancer cells to identify their vulnerabilities and discover new therapeutic targets. He leads the 平特五不中 Platform for Cellular Perturbation (MPCP), a pioneering technology platform that conducts functional genomics screens using a range of molecular tools, including CRISPR/Cas9 gene editing systems.
Publication highlights:
- SMARCA4 loss is synthetic lethal with CDK4/6 inhibition in non-small cell lung cancer. Xue Y, et al. Nat Commun. 2019 Feb 4;10(1):557. doi: 10.1038/s41467-019-08380-1. PMID: 30718506
- CD44 Promotes PD-L1 Expression and Its Tumor-Intrinsic Function in Breast and Lung Cancers. Kong T, et al. Cancer Res. 2020 Feb 1;80(3):444-457. doi: 10.1158/0008-5472.CAN-19-1108. PMID: 31722999
- SMARCA4/2 loss inhibits chemotherapy-induced apoptosis by restricting IP3R3-mediated Ca2+ flux to mitochondria. Xue Y, et al. Nat Commun. 2021 Sep 13;12(1):5404. doi: 10.1038/s41467-021-25260-9. PMID: 34518526
听
Prof. William Muller discovered that the cancer-causing gene ERBB2, or HER2, is activated in a proportion of lung cancers and other cancer types through a novel class of mutations that affect the way mature messenger RNA (mRNA) is produced from the ERBB2 gene, a process known as 鈥渁lternative splicing鈥�. Lung cancers that are caused by defects in ERBB2 alternative splicing may benefit from treatment with well-established anti-ERBB2 targeted therapies.
Publication highlights:
- An ErbB2 splice variant lacking exon 16 drives lung carcinoma. Smith HW, et al. Proc Natl Acad Sci U S A. 2020 Aug 18;117(33):20139-20148. doi: 10.1073/pnas.2007474117. PMID: 32727899
听