Therapeutic resistance in cancer is responsible for numerous cancer deaths in clinical practice. While target mutations are well recognized as the basis of genetic resistance to targeted therapy, nontarget mutation resistance (or nongenetic resistance) remains poorly characterized. Despite its complex and unintegrated mechanisms in the literature, nongenetic resistance is considered from our perspective to be a collective response of innate or acquired resistant subpopulations in heterogeneous tumors to therapy. These subpopulations, e.g., cancer stem-like cells, cancer cells with epithelial-to-mesenchymal transition, and drug-tolerant persisters, are protected by their resistance traits at cellular and molecular levels. This review summarizes recent advances in the research on resistant populations and their resistance traits. NOTCH signaling, as a central regulator of nongenetic resistance, is discussed with a special focus on its canonical maintenance of resistant cancer cells and noncanonical regulation of their resistance traits. This novel view of canonical and noncanonical NOTCH signaling pathways is translated into our proposal of reshaping therapeutic strategies targeting NOTCH signaling in resistant cancer cells. We hope that this review will lead researchers to study the canonical and noncanonical arms of NOTCH signaling as an integrated resistant mechanism, thus promoting the development of innovative therapeutic strategies.
Neoplasms/metabolism* ; Receptors, Notch/metabolism* ; Disease Resistance/physiology* ; Signal Transduction/physiology* ; Humans ; Drug Resistance, Neoplasm/physiology* ; Molecular Targeted Therapy/methods*

More than 80％ of lung cancer is non-small cell lung cancer (NSCLC),and the epidermal growth factor receptor (EGFR)-mediated signaling pathway is closely related to the occurrence and development of NSCLC.Small molecule EGFR-tyrosine kinase inhibitors (EGFR-TKI) targeting EGFR have been used in the clinical treatment of NSCLC,and positron emission tomography/computed tomgraphy (PET/CT) imaging can noninvasively monitor the expression and mutation status of EGFR in patients with NSCLC.18F-FDG PET/CT imaging has predictive value for the activation of EGFR mutation and EGFR-TKI treatment efficacy,and in vivo can be directly observed drugs and systemic tumor targeting EGFR combined with the specific circumstances,by PET/CT imaging before and after treatment,to achieve dynamic monitoring,guide the therapy before treatment and treatment of sensitive population screening process,to achieve NSCLC EGFR-TKI precise treatment is essential.

Objective:To explore the effects of body mass index (BMI) and gender on primary lung cancer 18F-FDG uptake param-eters, standardized uptake value (SUV), and standard uptake value of lean body mass (SUL). Methods:Data of 50 patients with prima-ry lung cancer confirmed by 18F-FDG positron emission tomography (PET)/computed tomography (CT) were retrospectively analyzed. AW4.6 workstation was employed to measure the SUVmean and SUVmax. Meanwhile, PETVCAR (PET Volume Computed Assisted Reading, GE Healthcare) software was used to automatically measure the SULmean, SULmax, and SULpeak. The SUVmean, SUV-max, SULmean, and SULmax of the liver (central region of the right lobe) were also measured automatically by PETVCAR. Afterward, T/N ratios (lesion SUVmax/liver SUVmean, lesion SULmax/liver SULmean, and lesion SULpeak/liver SULmean) of the lung cancer lesions were calculated. Correlations of the 18F-FDG metabolic parameters with BMI and gender of the patients were analyzed. Results:Liver SUVmean and SUVmax demonstrated significant positive correlations with BMI in all the patients (γ=0.38 and 0.36, P<0.05), and the SUVmean and SUVmax were positively correlated with BMI in male and female groups (γ=0.47 and 0.44, P<0.05), respective-ly. By contrast, no correlation existed between the liver SULmean and SULmax and BMI (P>0.05). No significant correlation was not-ed between the SUVmean, SUVmax, SULmean, SULmax, and SULpeak of the lung cancer lesions and BMI (P>0.05). The correlation trend is the same as that in different gender groups. Only the SUVmax T/N ratio of the lung cancer lesions showed a significant nega-tive correlation with BMI (γ=?0.29, P<0.05). The T/N ratios did not correlate with BMI in the different gender groups (P>0.05). Con-clusion:Patient BMI and gender mainly affect SUV values, particularly SUVmax, by contrast, patient BMI and gender did not signifi-cantly influence SUL and T/N ratio (SUL). Hence, SUL can be more suitable to quantitatively analyze and assess treatment response ob-jectively. This result will be helpful to the clinical application and promotion of PERCIST, which evaluates treatment response mainly by SUL.

Objective To evaluate the role of 18F fluorodeoxyglucose positron emission tomography computed tomography (PET-CT) in nasopharyngeal carcinoma (NPC) after radiotherapy. Methods A total of 27 NPC patients received 18FDG PET-CT 8-32 weeks after radiotherapy. All the patients were followed up for about 12 months after the examination. Metastasis and residual were evaluated by PET-CT. The correlation between SUV and prognosis was analyzed. Results Of these 27 patients, metastasis was found in 2 patients by PET-CT. Local persistence was diagnosed as for SUV≥2. 5 by PET-CT in 20 patients, among whom 18 were confirmed by biopsy and then received brachytherapy or conformal radiotherapy. One year local control and survival rates were 70% and 81%. Based on SUV, the patients were divided into group one for SUV between 2. 5 and 5(9 patients) or group two for SUV≥5 (11 patients). In group one and group two, the one year local control rate, survival rate and metastasis rate were 67% , 55% (P=0.670) , 64% ,89%(P=0.319), and 22% , 82% (P =0. 022) , respectively. Conclusions PET-CT is valuable for the identification of residual nasopharyngeal carcinoma. SUV of residual tumor is related to metastasis.