The crosstalk between autophagy and ferroptosis:what can we learn to target drug resistance in cancer?

Autophagy is a conserved intracellular degradation system that plays a dual role in cell death;thus,therapies targeting autophagy in cancer are somewhat controversial.Ferroptosis is a new form of regulated cell death featured with the iron-dependent accumulation of lethal lipid ROS.This pathway is morphologically,biochemically and genetically distinct from other forms of cell death.Accumulating studies have revealed crosstalk between autophagy and ferroptosis at the molecular level.In this review,we summarize the mechanisms of ferroptosis and autophagy,and more importantly,their roles in the drug resistance of cancer.Numerous connections between ferroptosis and autophagy have been revealed,and a strong causal relationship exists wherein one process controls the other and can be utilized as potential therapeutic targets for cancer.The elucidation of when and how to modulate their crosstalk using therapeutic strategies depends on an understanding of the fine-tuned switch between ferroptosis and autophagy,and approaches designed to manipulate the intensity of autophagy might be the key.

prevalence of colorectal neoplasms in young, average risk individuals: A turning tide between East and West

AIM To determine the prevalence of colorectal neoplasia in average risk persons 40-59 years of age in Israel and to compare the results with other populations. METHODS We reviewed the results of asymptomatic average-risk subjects, aged 40 to 59 years, undergoing their first screening colonoscopy between April 1994 and January 2014. The detection rates of adenoma, advanced adenoma(AA) and colorectal cancer(CRC) were determined in the 40's and 50's age groups by gender. The prevalence of lesions was compared between age groups. After meticulous review of the literature, these results were compared to published studies addressing the prevalence of colorectal neoplasia in similar patient groups, in a variety of geographical locations.RESULTS We included first screening colonoscopy results of 1750 individuals. The prevalence of adenomas, AA and CRC was 8.3%, 1.0% and 0.2% in the 40-49 age group and 13.7%, 2.4% and 0.2% in the 50-59 age group, respectively. Age-dependent differences in adenoma and AA rates were significant only among men(p < 0.005). Literature review disclosed 17 relevant studies. As expected, in both Asian and Western populations, the risks for overall adenoma and advanced adenoma was significantly higher in the 50's age group as compared to the 40's age group in a similar fashion. The result of the current study were similar to previous studies on Western populations. A substantially higher rate of adenoma, was observed in studies conducted among Asian populations in both age groups.CONCLUSION The higher rate of colorectal neoplasia in Asian populations requires further investigation and reconsideration as to the starting age of screening in that population.

Incidence of colorectal neoplasms among male pilots

AIM: To assess the prevalence of colorectal neoplasms (adenomas, advanced adenomas and colorectal cancers) among Israeli military and commercial airline pilots.

Primary Leiomyosarcoma of the Ovary: A Case Report

Leiomyosarcoma of the ovary is a rare disease, with aggressive behavior and poor prognosis, which mainly occurs in postmenopausal women. Surgery is the cornerstone of treatment, while the role of chemotherapy and radiotherapy is still not clear because substantial data is lacking. This paper presents the case of an adult woman who is diagnosed with primary leiomyosarcoma of the left ovary, and who receives a surgical approach and adjuvant treatment with chemotherapy currently achieving 20 months free from disease.

Resistance to immune checkpoint inhibitors in KRAS-mutant non-small cell lung cancer

Non-small cell lung cancer(NSCLC)patients with Kirsten rat sarcoma viral oncogene homolog(KRAS)mutation are associated with significant clinical heterogeneity and a poor prognosis to standard NSCLC therapies such as surgical resection,radiotherapy,chemotherapies,and targeted medicines.However,the application of immune checkpoints inhibitors(ICIs)has dramatically altered the therapeutic pattern of NSCLC management.Clinical studies have indicated that some KRAS-mutant NSCLC patients could benefit from ICIs;however,the responses in some patients are still poor.This review intends to elucidate the mechanisms of resistance to immunotherapy in KRAS-driven NSCLC and highlight the TME functions altered by immunoinhibitors,immunostimulators,and cancer metabolism.These metabolic pathways could potentially be promising approaches to overcome immunotherapy resistance.