<i>KRAS</i>
          G12C Mutation Is Associated with Increased Risk of Recurrence in Surgically Resected Lung Adenocarcinoma

Jones, Gregory D.; Caso, Raul; Tan, Kay See; Mastrogiacomo, Brooke; Sánchez-Vega, Francisco; Liu, Yuan; Connolly, James G.; Murciano‐Goroff, Yonina R.; Bott, Matthew; Adusumilli, Prasad S.; Molena, Daniela; Rocco, Gaetano; Rusch, Valerie W.; Sihag, Smita; Misale, Sandra; Yaeger, Rona; Drilon, Alexander; Arbour, Kathryn C.; Riely, Gregory J.; Rosen, Neal; Lito, Piro; Zhang, Haiying; Lyden, David; Rudin, Charles M.; Li, Bob T.; Isbell, James M.

doi:10.1158/1078-0432.ccr-20-4772

Cited by 22 publications

(37 citation statements)

References 41 publications

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“…It has been shown that co-alterations of STK11/LKB1 and KEAP1 were significantly associated with lung tumors [49,63,64]. One explanation is the proximity of the corresponding genomic loci on the short arm of chromosome 19 (at 19p13.2 for KEAP1 and 19p13.3 for STK11/LKB1).…”

Section: Stk11/lkb1 Alterations Promote Lung Cancer Cell Survival And...mentioning

confidence: 99%

STK11/LKB1 Modulation of the Immune Response in Lung Cancer: From Biology to Therapeutic Impact

Pons‐Tostivint

Lugat

Fontenau

et al. 2021

Cells

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The STK11/LKB1 gene codes for liver kinase B1 (STK11/LKB1), a highly conserved serine/threonine kinase involved in many energy-related cellular processes. The canonical tumor-suppressive role for STK11/LKB1 involves the activation of AMPK-related kinases, a master regulator of cell survival during stress conditions. In pre-clinical models, inactivation of STK11/LKB1 leads to the progression of lung cancer with the acquisition of metastatic properties. Moreover, preclinical and clinical data have shown that inactivation of STK11/LKB1 is associated with an inert tumor immune microenvironment, with a reduced density of infiltrating cytotoxic CD8+ T lymphocytes, a lower expression of PD-(L)1, and a neutrophil-enriched tumor microenvironment. In this review, we first describe the biological function of STK11/LKB1 and the role of its inactivation in cancer cells. We report descriptive epidemiology, co-occurring genomic alterations, and prognostic impact for lung cancer patients. Finally, we discuss recent data based on pre-clinical models and lung cancer cohorts analyzing the results of STK11/LKB1 alterations on the immune system and response or resistance to immune checkpoint inhibitors.

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Section: Stk11/lkb1 Alterations Promote Lung Cancer Cell Survival And...mentioning

confidence: 99%

STK11/LKB1 Modulation of the Immune Response in Lung Cancer: From Biology to Therapeutic Impact

Pons‐Tostivint

Lugat

Fontenau

et al. 2021

Cells

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“…The genes included in the molecular typing of LUAD often include EGFR, ALK, ROS1, BRAF, NTRK1/2/3, MET, and RET, and the mutation rate of functional driver genes is about 60%, among which KRAS, EGFR mutations and EML4-ALK fusion is the most common driver gene, accounting for about 35% to 40% (23)(24)(25). The study by Jones et al showed that KRAS G12C mutation was associated with worse disease-free survival after complete resection of stage I-III LUAD (26).…”

Section: Discussionmentioning

confidence: 99%

P2RY14 downregulation in lung adenocarcinoma: a potential therapeutic target associated with immune infiltration

Xu¹,

Xu²,

Yao³

et al. 2022

J Thorac Dis

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Background: The current study aimed to investigate the interrelation between P2RY14 and the prognosis of patients suffering from lung adenocarcinoma (LUAD) following surgery. Methods:The differentially expressed gene (DEG) P2RY14 was screened by the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and Immunology Database and Analysis Portal (ImmPort) databases. The relationship between P2RY14 and clinical data of LUAD was analyzed in TCGA and Kaplan-Meier (KM)-plotter databases. The association of P2RY14 with immune cells and immune-related expressed genes was analyzed in the Tumor Immune Estimation Resource (TIMER) database. A retrospective analysis of the 100 patients clinical data undergoing pulmonary adenocarcinoma surgery admitted to Nanjing Chest Hospital.Immunohistochemistry (IHC) analysis was carried out to evaluate the P2RY14 expression in lung cancer tissues, and quantitative reverse transcription PCR (RT-qPCR) was used to confirm the mRNA expression of this gene in LUAD tissues. And their survival was evaluated. KM method and the log-rank test were used for univariate survival analysis, and the Cox regression method was employed for multivariate survival analysis.Results: P2Y14 was the DEG identified by the database. P2Y14 expression was upregulated in para-cancer tissues in comparison to cancer tissues. Patients suffering from LUAD who have high P2RY14 expression had a better prognosis than those with low expression. P2RY14 expression was shown to be substantially linked with immune invasion in the TIMER database. Finally, the trial included 100 patients, of which 80 died and 20 survived with a mean overall survival (OS) of 48 months. Between the high and low expression groups of P2RY14, there were statistically significant variations in the clinical stage and differentiation degree (P<0.05).Cox regression analysis revealed that differentiation degree, smoking history, and P2RY14 expression were independent risk factors for the prognosis of LUAD patients (all P<0.05).Conclusions: P2RY14 can substantially prolong the OS of patients suffering from LUAD and can be utilized as a new LUAD predictive biomarker. P2RY14 may be related to LUAD immune invasion and have an essential role in inhibiting tumor cell immune escape within the LUAD microenvironment.

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“… 40 , 41 Additionally, patients with specific gene mutation show worse prognosis than patients with wild‐type genotype. 42 EGFR mutation‐positive NSCLC, targeted therapy as adjuvant treatment, has improved the survival of NSCLC patients. For instance, the 24‐month DFS is 89% in osimertinib group versus 52% in the placebo group, with reduced local relapse and metastasis.…”

Section: Clinical Management Of Nsclcmentioning

confidence: 99%

Therapeutic advances in non‐small cell lung cancer: Focus on clinical development of targeted therapy and immunotherapy

Yuan

Zhang

2021

MedComm

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Lung cancer still contributes to nearly one‐quarter cancer‐related deaths in the past decades, despite the rapid development of targeted therapy and immunotherapy in non‐small cell lung cancer (NSCLC). The development and availability of comprehensive genomic profiling make the classification of NSCLC more precise and personalized. Most treatment decisions of advanced‐stage NSCLC have been made based on the genetic features and PD‐L1 expression of patients. For the past 2 years, more than 10 therapeutic strategies have been approved as first‐line treatment for certain subgroups of NSCLC. However, some major challenges remain, including drug resistance and low rate of overall survival. Therefore, we discuss and review the therapeutic strategies of NSCLC, and focus on the development of targeted therapy and immunotherapy in advanced‐stage NSCLC. Based on the latest guidelines, we provide an updated summary on the standard treatment for NSCLC. At last, we discussed several potential therapies for NSCLC. The development of new drugs and combination therapies both provide promising therapeutic effects on NSCLC.

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KRAS G12C Mutation Is Associated with Increased Risk of Recurrence in Surgically Resected Lung Adenocarcinoma

Cited by 22 publications

References 41 publications

STK11/LKB1 Modulation of the Immune Response in Lung Cancer: From Biology to Therapeutic Impact

STK11/LKB1 Modulation of the Immune Response in Lung Cancer: From Biology to Therapeutic Impact

P2RY14 downregulation in lung adenocarcinoma: a potential therapeutic target associated with immune infiltration

Therapeutic advances in non‐small cell lung cancer: Focus on clinical development of targeted therapy and immunotherapy

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