Journal ArticleDOI
Metabolic networks in mutant KRAS-driven tumours: tissue specificities and the microenvironment.
TLDR
In this paper, convergent and disparate metabolic networks regulated by oncogenic mutant KRAS in colon, lung and pancreas tumours, with an emphasis on cooccurring mutations and the role of the tumour microenvironment.Abstract:
Oncogenic mutations in KRAS drive common metabolic programmes that facilitate tumour survival, growth and immune evasion in colorectal carcinoma, non-small-cell lung cancer and pancreatic ductal adenocarcinoma. However, the impacts of mutant KRAS signalling on malignant cell programmes and tumour properties are also dictated by tumour suppressor losses and physiological features specific to the cell and tissue of origin. Here we review convergent and disparate metabolic networks regulated by oncogenic mutant KRAS in colon, lung and pancreas tumours, with an emphasis on co-occurring mutations and the role of the tumour microenvironment. Furthermore, we explore how these networks can be exploited for therapeutic gain.read more
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KRAS mutation: from undruggable to druggable in cancer
TL;DR: In this article, a review summarises the most recent understanding of fundamental aspects of KRAS, the relationship between the KRAS mutations and tumour immune evasion, and new progress in targeting KRAS (G12C) particularly KRAS.
Journal ArticleDOI
Lineage tracing reveals the phylodynamics, plasticity, and paths of tumor evolution
Dian Yang,Matthew G. Jones,Santiago Naranjo,William M. Rideout,Kyung Hoi Min,Raymond Ho,Wei Wu,Joseph M. Replogle,Jennifer L. Page,Jeffrey J. Quinn,Felix Horns,Xiaojie Qiu,Michael Z. Chen,William A. Freed-Pastor,Christopher S. McGinnis,David M. Patterson,Zev J. Gartner,Eric D. Chow,Trever G. Bivona,Michelle Chan,Nir Yosef,Tyler Jacks,Jonathan S. Weissman +22 more
TL;DR: In this article , an evolving lineage-tracing system with a single-cell RNA-seq readout was introduced into a mouse model of Kras;Trp53(KP)-driven lung adenocarcinoma and tracked tumor evolution from single-transformed cells to metastatic tumors at unprecedented resolution.
Journal ArticleDOI
Targeting oncogene and non-oncogene addiction to inflame the tumour microenvironment
TL;DR: Both oncogene and non-oncogene addiction stand out as promising targets to robustly inflame the TME and potentially enable superior responses to ICIs.
Journal ArticleDOI
Non-Small-Cell Lung Cancer in 2022: A Review for General Practitioners in Oncology
TL;DR: A contemporary review of treatment of non-small cell lung cancer in Canada based on current best practices is presented, with a special focus on the incorporation of immunotherapy into practice and its associated toxicities.
Journal ArticleDOI
Glutaminase inhibition impairs CD8 T cell activation in STK11-/Lkb1-deficient lung cancer.
Sarah A. Best,Patrick Gubser,Shalini Sethumadhavan,Ariena Kersbergen,Yashira L Negrón Abril,Joshua E. Goldford,Katherine Sellers,Waruni Abeysekera,Alexandra L. Garnham,Jackson A McDonald,Clare E. Weeden,Dovile Anderson,David Pirman,Thomas P. Roddy,Darren J. Creek,Axel Kallies,Gillian Kingsbury,Kate D. Sutherland +17 more
TL;DR: In this article , the metabolic and immune microenvironment of KRAS-mutant lung adenocarcinoma was investigated in the context of anti-PD1 immunotherapy.
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TL;DR: New-generation combinatorial therapies may overcome resistance mechanisms to immune checkpoint therapy, and evidence points to alterations that converge on the antigen presentation and interferon-γ signaling pathways.
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