Targeted therapy in advanced non-small cell lung cancer: current advances and future trends

Majeed, Umair; Manochakian, Rami; Zhao, Yujie; Lou, Yanyan

doi:10.1186/s13045-021-01121-2

Cited by 169 publications

(127 citation statements)

References 119 publications

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“…Lung cancer remains the leading cause of cancer-associated mortality [ 1 , 2 ], while small-cell lung cancer (SCLC) comprises approximately 15% of these cases [ 3 ]. SCLC is characterized by poor prognosis with a 5-year survival rate of less than 7% [ 4 ].…”

Section: To the Editormentioning

confidence: 99%

m6A regulators as predictive biomarkers for chemotherapy benefit and potential therapeutic targets for overcoming chemotherapy resistance in small-cell lung cancer

Zhang

Yang

et al. 2021

J Hematol Oncol

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Small-cell lung cancer (SCLC) is a devastating subtype of lung cancer with few therapeutic options. Despite the advent of immunotherapy, platinum-based chemotherapy is still the irreplaceable first-line therapy for SCLCs. However, drug resistance will invariably occur in most patients and the outcomes are heterogeneous. Therefore, clinically feasible classification strategies and potential therapeutic targets for overcoming chemotherapy resistance are urgently needed. N6-methyladenosine (m6A) is a novel epigenetic decisive factor that is involved in tumor progression and drug resistance. However, almost nothing is known about m6A modification in SCLC. Here, we assessed 200 SCLC samples from patients who underwent chemotherapy from three different cohorts, including a validation cohort containing 71 cases with qPCR data and an independent cohort containing 79 cases with immunohistochemistry data (quantified as H-score). We systematically characterized the predictive landscape of m6A regulators in SCLC patients following with chemotherapy. Using the LASSO Cox model, we built a seven-regulator-based (ZCCHC4, IGF2BP3, ALKBH5, YTHDF3, METTL5, G3BP1, and RBMX) chemotherapy benefit predictive classifier (m6A score) and subsequently validated the classifier in two other cohorts. Time-dependent ROC and C-index analyses showed that the m6A score to possessed superior predictive power for chemotherapy benefit in comparison with other clinicopathological parameters. A multicohort multivariate analysis revealed that the m6A score is an independent factor that affects survival benefit across multiple cohorts. Our in vitro experimental results revealed that three regulators—ZCCHC4, G3BP1, and RBMX—may serve as promising novel therapeutic targets for overcoming chemoresistance in SCLCs. Our results, for the first time, demonstrate the predictive significance of m6A regulators for chemotherapy benefit, as well as their potential as therapeutic targets for overcoming chemotherapy resistance in SCLC patients. The m6A score was found to be a reliable prognostic tool that may help guide chemotherapy decisions for patients with SCLC.

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Section: To the Editormentioning

confidence: 99%

m6A regulators as predictive biomarkers for chemotherapy benefit and potential therapeutic targets for overcoming chemotherapy resistance in small-cell lung cancer

Zhang

Yang

et al. 2021

J Hematol Oncol

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“…After the approval of modern biological therapy, the number of deaths was substantially reduced. However, there are special problems because the disease continues to progress in most cases, due to the development of drug resistance [177][178][179].…”

Section: Lung Cancermentioning

confidence: 99%

Latest Innovations and Nanotechnologies with Curcumin as a Nature-Inspired Photosensitizer Applied in the Photodynamic Therapy of Cancer

Ailioaie

Litscher

2021

Pharmaceutics

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In the context of the high incidence of cancer worldwide, state-of-the-art photodynamic therapy (PDT) has entered as a usual protocol of attempting to eradicate cancer as a minimally invasive procedure, along with pharmacological resources and radiation therapy. The photosensitizer (PS) excited at certain wavelengths of the applied light source, in the presence of oxygen releases several free radicals and various oxidation products with high cytotoxic potential, which will lead to cell death in irradiated cancerous tissues. Current research focuses on the potential of natural products as a superior generation of photosensitizers, which through the latest nanotechnologies target tumors better, are less toxic to neighboring tissues, but at the same time, have improved light absorption for the more aggressive and widespread forms of cancer. Curcumin incorporated into nanotechnologies has a higher intracellular absorption, a higher targeting rate, increased toxicity to tumor cells, accelerates the activity of caspases and DNA cleavage, decreases the mitochondrial activity of cancer cells, decreases their viability and proliferation, decreases angiogenesis, and finally induces apoptosis. It reduces the size of the primary tumor, reverses multidrug resistance in chemotherapy and decreases resistance to radiation therapy in neoplasms. Current research has shown that the use of PDT and nanoformulations of curcumin has a modulating effect on ROS generation, so light or laser irradiation will lead to excessive ROS growth, while nanocurcumin will reduce the activation of ROS-producing enzymes or will determine the quick removal of ROS, seemingly opposite but synergistic phenomena by inducing neoplasm apoptosis, but at the same time, accelerating the repair of nearby tissue. The latest curcumin nanoformulations have a huge potential to optimize PDT, to overcome major side effects, resistance to chemotherapy, relapses and metastases. All the studies reviewed and presented revealed great potential for the applicability of nanoformulations of curcumin and PDT in cancer therapy.

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“…Targeting epidermal growth factor receptor (EGFR) is one of the important treatments for OSCC, lung cancer and other tumors, and has shown good clinical effects ( 11 ). Cetuximab combined with radiotherapy and chemotherapy is one of the recommended therapies in the NCCN tumor treatment guidelines for the treatment of advanced tumors, including OSCC ( 12 , 13 ).…”

Section: Introductionmentioning

confidence: 99%

Metformin Downregulates the Expression of Epidermal Growth Factor Receptor Independent of Lowering Blood Glucose in Oral Squamous Cell Carcinoma

et al. 2022

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PurposeType 2 diabetes mellitus (T2DM) is among the risk factors for the occurrence and development of cancer. Metformin is a potential anticancer drug. Epidermal growth factor receptor (EGFR) plays an important role in the progression of oral squamous cell carcinoma(OSCC), but the relationship between metformin and EGFR expression in OSCC remains unclear.MethodsThis study involved the immunohistochemical detection of EGFR expression in cancer tissues of patients with T2DM and OSCC. The patients were divided into groups according to whether they were taking metformin for the treatment of T2DM, and the expression of EGFR in different groups was compared. Correlation analysis between the expression of EGFR and the fluctuation value of fasting blood glucose (FBG) was carried out. Immunohistochemistry was used to detect the expression of EGFR in cancer tissues of patients with recurrent OSCC. These patients had normal blood glucose and took metformin for a long time after the first operation.ResultsEGFR expression in T2DM patients with OSCC taking metformin was significantly lower than that in the non-metformin group. FBG fluctuations were positively correlated with the expression of EGFR in the OSCC tissues of the non-metformin group of T2DM patients. In patients with recurrent OSCC with normal blood glucose, metformin remarkably reduced the expression of EGFR in recurrent OSCC tissues.ConclusionMetformin may regulate the expression of EGFR in a way that does not rely on lowering blood glucose. These results may provide further evidence for metformin in the treatment of OSCC.

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Targeted therapy in advanced non-small cell lung cancer: current advances and future trends

Cited by 169 publications

References 119 publications

m6A regulators as predictive biomarkers for chemotherapy benefit and potential therapeutic targets for overcoming chemotherapy resistance in small-cell lung cancer

m6A regulators as predictive biomarkers for chemotherapy benefit and potential therapeutic targets for overcoming chemotherapy resistance in small-cell lung cancer

Latest Innovations and Nanotechnologies with Curcumin as a Nature-Inspired Photosensitizer Applied in the Photodynamic Therapy of Cancer

Metformin Downregulates the Expression of Epidermal Growth Factor Receptor Independent of Lowering Blood Glucose in Oral Squamous Cell Carcinoma

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