The Resistance Mechanisms of Lung Cancer Immunotherapy

Wang, Fen; Wang, Shubin; Zhou, Qing

doi:10.3389/fonc.2020.568059

Cited by 57 publications

(114 citation statements)

References 336 publications

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“…Moderate immune responses to a tumor or their complete absence are explained by the absence of expression of foreign genes in tumor cells. In addition, if the tumor mutation burden, the level of DNA mismatch repair, and genomic microsatellite instability are low, the production of tumor antigens will be reduced, which may lead to drug resistance [69]. This can also cause anatomical isolation of tumor antigens from the immune system (in particular, due to the additional barriers for brain tumors-BBB and BBTB) or generalized immunosuppression in a cancer patient.…”

Section: Immune Evasionmentioning

confidence: 99%

Molecular Mechanisms of Drug Resistance in Glioblastoma

Дымова

Kuligina

Richter

2021

IJMS

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Glioblastoma multiforme (GBM) is the most common and fatal primary brain tumor, is highly resistant to conventional radiation and chemotherapy, and is not amenable to effective surgical resection. The present review summarizes recent advances in our understanding of the molecular mechanisms of therapeutic resistance of GBM to already known drugs, the molecular characteristics of glioblastoma cells, and the barriers in the brain that underlie drug resistance. We also discuss the progress that has been made in the development of new targeted drugs for glioblastoma, as well as advances in drug delivery across the blood–brain barrier (BBB) and blood–brain tumor barrier (BBTB).

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Section: Immune Evasionmentioning

confidence: 99%

Molecular Mechanisms of Drug Resistance in Glioblastoma

Дымова

Kuligina

Richter

2021

IJMS

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“…Epigenetic modifications are associated with anticancer immunity, including T cell function, migration, exhaustion, and neoantigen expression ( Wang et al, 2020 ). Epigenetic modifications silence tumor suppressor and apoptosis genes, thereby activating tumor proliferation ( Table 1 ) ( Baxter et al, 2014 ).…”

Section: Mechanisms Of Acquired Resistance To Anti–pd-1/pd-l1mentioning

confidence: 99%

Clinical Perspectives to Overcome Acquired Resistance to Anti–Programmed Death-1 and Anti–Programmed Death Ligand-1 Therapy in Non-Small Cell Lung Cancer

Lee

et al. 2021

Molecules and Cells

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Immune checkpoint inhibitors have changed the paradigm of treatment options for non-small cell lung cancer (NSCLC).Monoclonal antibodies targeting programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) have gained wide attention for their application, which has been shown to result in prolonged survival. Nevertheless, only a limited subset of patients show partial or complete response to PD-1 therapy, and patients who show a response eventually develop resistance to immunotherapy. This article aims to provide an overview of the mechanisms of acquired resistance to anti-PD-1/PD-L1 therapy from the perspective of tumor cells and the surrounding microenvironment. In addition, we address the potential therapeutic targets and ongoing clinical trials, focusing mainly on NSCLC.

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“…Additionally, another study showed a higher prolonged progression-free survival in anti-PD-1-treated patients harboring TP53 -mut/ STK11 - EGFR -wt tumors than in patients with TP53 -wt/ STK11 -mut [ 111 ]. A few initial studies demonstrated that mutated STK11 tumors, notably with TP53 , KRAS and KEAP1 mutations, showed primary resistance to ICIs [ 15 , 53 , 57 ]. Using whole-exome sequencing to examine NSCLC patients treated with PD-1 plus CTLA-4 blockade, a study demonstrated that a couple of patients with a STK11 mutation had primary resistance to this therapeutic combination [ 6 ].…”

Section: Stk11 As a Predictive Biomarker For Thmentioning

confidence: 99%

“…In line with the tremendous clinical progress, the understanding of the efficacy of immunotherapy in NSCLC and its pathophysiology has unraveled new cellular mechanisms associated with its response to treatment and to intrinsic resistance [ 12 , 13 , 14 , 15 ]. Moreover, bioinformatic analyses are becoming increasingly sophisticated allowing the analysis and integration of complex clinical and biological data to further understand the biology of cancer, notably of lung carcinoma [ 16 , 17 , 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

The Importance of STK11/LKB1 Assessment in Non-Small Cell Lung Carcinomas

2021

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Despite the recent implementation of immunotherapy as a single treatment or in combination with chemotherapy for first-line treatment of advanced non-small cell lung cancer (NSCLC), many patients do not benefit from this regimen due to primary treatment resistance or toxicity. Consequently, there is an urgent need to develop efficient biomarkers that can select patients who will benefit from immunotherapy thereby providing the appropriate treatment and avoiding toxicity. One of the biomarkers recently described for the stratification of NSCLC patients undergoing immunotherapy are mutations in STK11/LKB1, which are often associated with a lack of response to immunotherapy in some patients. Therefore, the purpose of this review is to describe the different cellular mechanisms associated with STK11/LKB1 mutations, which may explain the lack of response to immunotherapy. Moreover the review addresses the co-occurrence of additional mutations that may influence the response to immunotherapy and the current clinical studies that have further explored STK11/LKB1 as a predictive biomarker. Additionally this work includes the opportunities and limitations to look for the STK11/LKB1 status in the therapeutic strategy for NSCLC patients.

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The Resistance Mechanisms of Lung Cancer Immunotherapy

Cited by 57 publications

References 336 publications

Molecular Mechanisms of Drug Resistance in Glioblastoma

Molecular Mechanisms of Drug Resistance in Glioblastoma

Clinical Perspectives to Overcome Acquired Resistance to Anti–Programmed Death-1 and Anti–Programmed Death Ligand-1 Therapy in Non-Small Cell Lung Cancer

The Importance of STK11/LKB1 Assessment in Non-Small Cell Lung Carcinomas

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