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The discovery of the efficacy of tyrosine kinase inhibitors (TKIs) in epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) patients has revolutionized lung cancer therapy. Although almost all responders acquire drug resistance within a few years, many studies have revealed several acquired-resistant mechanisms and developed therapeutic strategies countervailing them, most notably against the EGFR T790M gatekeeper mutation. However, little progress has been made in terms of elucidating the mechanisms of primary resistance. Primary resistance may be defined into two types of resistance, clinically representing patients that do not respond (non-responders) to EGFR-TKIs. The first group consists of approximately 10% of patients that are insensitive to EGFR-TKIs from the outset (intrinsic primary resistance), and 20–30% of the second group consists of patients that seem to clinically benefit at first, but experience early relapse within six months (late primary resistance). In this review, we first provide an overview of drug-induced lung cancer dynamics. We then delve into the mechanisms of primary resistance, with a primary focus on two specific subtypes of resistance. We suggest that “intrinsic primary resistance” is characterized by pre-existing somatic and genomic changes and cell of origins, while “late primary resistance” is correlated with the drug-tolerant persister state. Developing therapeutic strategies to overcome primary resistance is crucial to prolonging the duration of EGFR-TKI therapy. Ultimately, this will allow for an enhanced understanding of lung cancer’s evolutional process, leading to the reversal of acquired resistance and the complete eradication of lung cancer.

Aim: Understanding the prevalence of antibiotic resistance can provide reliable information for selecting treatment options. The goal of this meta-analysis was to observe the primary antibiotic resistance of Helicobacter pylori (H. pylori) in different regions and time periods of China. Method: We searched PubMed, EMBASE, Chinese Biomedical databases and the China National Knowledge Infrastructure from inception to 20 February 2022. Data on the prevalence of H. pylori primary resistance at various time points were included. A random-effect model was established to calculate the pooled antibiotic resistance. Results: In total, 2150 articles were searched, with 70 meeting the inclusion criteria. The resistance to clarithromycin, metronidazole, levofloxacin amoxicillin, tetracycline and furazolidone in 2016–2020 were 34% (95% CI: 30–39%), 78% (95% CI: 73–84%), 35% (95% CI: 30–40%), 3% (95% CI: 1–5%), 2% (95%CI: 1–4%) and 1% (95% CI: 0–4%), respectively. Clarithromycin showed regional difference, as the resistance was higher in northern (37%, 95% CI: 32–41%) and western China (35%, 95% CI: 17–54%) than that in southern (24%, 95% CI: 17–32%) and eastern China (24%, 95% CI: 20–28%). Conclusion: The resistance of H. pylori to clarithromycin and metronidazole was high and increased over time, whereas resistance to levofloxacin, amoxicillin, tetracycline and furazolidone remained stable.

Immune checkpoint inhibitors (ICPis) have revolutionized cancer therapy with broad activities against a wide range of malignancies. However, in many malignancies their efficacy remains limited due to the primary resistance. Furthermore, a high percentage of patients develop progression due to the secondary resistance even after obtaining a response or achieving a stable disease. In this review, we will discuss the mechanisms that underlie the primary and secondary resistance to ICPis in cancer immunotherapy and provide an overview to impart a broad understanding of the critical issues that are encountered in clinical oncology practice.

Treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) improves the overall survival of patients with EGFR-mutated non-small-cell lung cancer (NSCLC). First-generation EGFR-TKIs (e.g., gefitinib and erlotinib) or second-generation EGFR-TKIs (e.g., afatinib and dacomitinib) are effective for the treatment of EGFR-mutated NSCLC, especially in patients with EGFR exon 19 deletions or an exon 21 L858R mutation. However, almost all cases experience disease recurrence after 1 to 2 years due to acquired resistance. The EGFR T790M mutation in exon 20 is the most frequent alteration associated with the development of acquired resistance. Osimertinib—a third-generation EGFR-TKI—targets the T790M mutation and has demonstrated high efficacy against EGFR-mutated lung cancer. However, the development of acquired resistance to third-generation EGFR-TKI, involving the cysteine residue at codon 797 mutation, has been observed. Other mechanisms of acquired resistance include the activation of alternative pathways or downstream targets and histological transformation (i.e., epithelial⁻mesenchymal transition or conversion to small-cell lung cancer). Furthermore, the development of primary resistance through overexpression of the hepatocyte growth factor and suppression of Bcl-2-like protein 11 expression may lead to problems. In this report, we review these mechanisms and discuss therapeutic strategies to overcome resistance to EGFR-TKIs.

Aim: Understanding the prevalence of antibiotic resistance can provide reliable information for selecting treatment options. The goal of this meta-analysis was to observe the primary antibiotic resistance of Helicobacter pylori ( H. pylori ) in different regions and time periods of China., Method: We searched PubMed, EMBASE, Chinese Biomedical databases and the China National Knowledge Infrastructure from inception to 20 February 2022. Data on the prevalence of H. pylori primary resistance at various time points were included. A random-effect model was established to calculate the pooled antibiotic resistance., Results: In total, 2150 articles were searched, with 70 meeting the inclusion criteria. The resistance to clarithromycin, metronidazole, levofloxacin amoxicillin, tetracycline and furazolidone in 2016-2020 were 34% (95% CI: 30-39%), 78% (95% CI: 73-84%), 35% (95% CI: 30-40%), 3% (95% CI: 1-5%), 2% (95%CI: 1-4%) and 1% (95% CI: 0-4%), respectively. Clarithromycin showed regional difference, as the resistance was higher in northern (37%, 95% CI: 32-41%) and western China (35%, 95% CI: 17-54%) than that in southern (24%, 95% CI: 17-32%) and eastern China (24%, 95% CI: 20-28%)., Conclusion: The resistance of H. pylori to clarithromycin and metronidazole was high and increased over time, whereas resistance to levofloxacin, amoxicillin, tetracycline and furazolidone remained stable.

Immune checkpoint inhibitors (ICPis) have revolutionized cancer therapy with broad activities against a wide range of malignancies. However, in many malignancies their efficacy remains limited due to the primary resistance. Furthermore, a high percentage of patients develop progression due to the secondary resistance even after obtaining a response or achieving a stable disease. In this review, we will discuss the mechanisms that underlie the primary and secondary resistance to ICPis in cancer immunotherapy and provide an overview to impart a broad understanding of the critical issues that are encountered in clinical oncology practice.