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A number of organizations are producing resource stratified guidelines (RSGs) for cancer. Despite using similar definitions of resource levels, systemic treatment recommendations often differ between organizations. We systematically searched for RSGs focusing on solid tumors. We qualitatively compared the methods used to generate guidelines using the AGREE‐II appraisal tool. We extracted systemic treatment recommendations and assessed interguideline concordance using the Gwet AC1 coefficient, stratified by resource level, treatment setting and cancer type. We identified 69 RSGs cancer covering 15 solid tumors produced by four organizations. Despite using common resource‐level definitions (Basic, Core/Limited, Enhanced and Maximal), recommendations differed between organizations. Concordance for chemotherapy recommendations was poor in Basic (58.3%, Gwet 0.20), fair in Core (58.3%, Gwet 0.32) and excellent in Enhanced (92.4%, Gwet 0.92) and Maximal settings (95.4%, Gwet 0.95). Concordance rates for endocrine therapy were good in Basic (80% Gwet 0.61), and excellent in Core (90%, Gwet 0.87), Enhanced (90%, Gwet 0.89) and Maximal settings (90%, Gwet 0.89). There was moderate to excellent concordance in targeted therapy recommendations across all resource levels. Differences in recommendations appeared driven by different opinions among the chosen panel of experts regarding what is resource appropriate. Overall, we found that countries looking to base treatment and health‐policy on RSGs will find conflicting information depending on which guidelines are used, particularly for chemotherapy in Basic and Core settings. Improved transparency regarding the methods used to determine the value of a therapy for a given resource level is needed. What's new? While resource‐stratified guidelines to inform the prioritization of cancer treatment are increasing globally, systemic treatment recommendations often differ from one organization to the next. Here, the authors compared resource‐stratified guidelines for systemic therapy of solid tumors produced by four different organizations. Guideline comparisons show that despite having similar goals and using a common resource framework, treatment recommendations vary across organizations. This is the case particularly for chemotherapy recommendations in limited‐resource settings. The findings suggest that more robust models incorporating greater information on resource constraints are needed to improve consistency in resource‐stratified guidelines between organizations and countries. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. A variety of factors can contribute to the onset of this disease, including viral infection, obesity, alcohol abuse and non-alcoholic fatty liver disease (NAFLD). These stressors predominantly introduce chronic inflammation leading to liver cirrhosis and finally the onset of HCC; however, approximately 20% of HCC cases arise in the absence of cirrhosis via a poorly defined mechanism. The atypical cyclin-like protein Spy1 is capable of overriding cell cycle checkpoints, promoting proliferation and has been implicated in HCC. We hypothesize that Spy1 promotes sustained proliferation making the liver more susceptible to accumulation of deleterious mutations, leading to the development of non-cirrhotic HCC. We report for the first time that elevation of Spy1 within the liver of a transgenic mouse model leads to enhanced spontaneous liver tumourigenesis. We show that the abundance of Spy1 enhanced fat deposition within the liver and decreased the inflammatory response. Interestingly, Spy1 transgenic mice have a significant reduction in fibrosis and sustained rates of hepatocyte proliferation, and endogenous levels of Spy1 are downregulated during the normal fibrotic response. Our results provide support that abnormal regulation of Spy1 protein drives liver tumorigenesis in the absence of elevated fibrosis and, hence, may represent a potential mechanism behind non-cirrhotic HCC. This work may implicate Spy1 as a prognostic indicator and/or potential target in the treatment of diseases of the liver, such as HCC. The cyclin-like protein Spy1 enhances lipid deposition and reduces fibrosis in the liver. Spy1 also promotes increased hepatocyte proliferation and onset of non-cirrhotic hepatocellular carcinoma (HCC). Thus, Spy1 may be used as a potential target in the treatment of HCC. [ABSTRACT FROM AUTHOR]

SUMMARY. Freud's'Dora'case is an example of hysteria in which the symptoms themselves are fundamentally id-phenomena modified and disguised. In other hysteria cases the symptoms may originate in the harsh superego and represent childhood punishments, reinvoked in a desperate effort to hold forbidden impulses in repression. Analytic interpretation of such symptoms can help to loosen the repressive barrier. At the same time the fact of reinvocation of childhood punishments can alert the analyst to the presence of forbidden impulses clamouring for expression. [ABSTRACT FROM AUTHOR]

The article discusses Estrogen receptor (ER)–positive, human epidermal growth factor receptor 2 (HER2)–negative (ER+/HER2−), the most common subtype of breast cancer, accounting for up to 70% of all cases diagnosed. Mentions estrogen drives cell proliferation by inducing the expression of cyclin D1 and activating the cyclin-dependent kinase 4/6 (CDK4/6) pathway, in ER+ breast cancer. Informs relapses of ER+/ HER2- breast cancer remain a major problem, comprising 60% of metastatic breast cancer.

Targeting complementary pathways in diseases such as cancer can be achieved with co-delivery of small interfering ribonucleic acid (siRNA) and small molecule drugs; however, current formulation strategies are typically limited to one, but not both. Here, ionizable small molecule drugs and siRNA are co-formulated in drug-rich nanoparticles. Ionizable analogs of the selective estrogen receptor degrader fulvestrant self-assemble into colloidal drug aggregates and cause endosomal disruption, allowing co-delivery of siRNA against a non-druggable target. siRNA is encapsulated in lipid-stabilized, drug-rich colloidal nanoparticles where the ionizable lipid used in conventional lipid nanoparticles is replaced with an ionizable fulvestrant analog. The selection of an appropriate phospholipid and formulation buffer enables endocytosis and potent reporter gene knockdown in cancer cells. Importantly, siRNA targeting cyclin E1 is effectively delivered to drug-resistant breast cancer cells, demonstrating the utility of this approach. This strategy opens the possibility of using ionizable drugs to co-deliver RNA and ultimately improve therapeutic outcomes., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Addressing the challenges of survivorship necessitates a comprehensive, patient-centered approach, focusing on mitigating risk through lifestyle modification, identifying distant recurrence, and optimization of breast imaging. This article will discuss the current and emerging clinical strategies for the survivorship period, advocating a multidisciplinary and comprehensive approach. In this manner, early-stage breast cancer survivors are empowered to navigate their journey with enhanced knowledge, facilitating a transition to life beyond cancer.

Immunotherapy continues to redefine the solid tumor treatment landscape, with inhibitors of the PD-L1/PD-1 immune checkpoint having the most widespread impact. As the most common cancer diagnosed worldwide, there is significant interest in the development of immunotherapy for the treatment of breast cancer in both the early and metastatic settings. Recently reported results of several clinical trials have identified potential roles for immunotherapy agents alone or in combination with standard treatment for early and metastatic disease. While trials to date have been promising, immunotherapy has only been shown to benefit a select group of patients with breast cancer, defined by tumor subtype, PD-L1 expression, and line of therapy. With over 250 trials ongoing, emerging data will enable the further refinement of breast cancer immunotherapy strategies. The integration of multiple putative biomarkers and consideration of dynamic markers of early response or resistance may inform optimal patient selection for immunotherapy investigation and integration into clinical practice. This review will summarize the current evidence for immune-checkpoint blockade (ICB) in the treatment of early and metastatic breast cancer, highlighting current and potential future biomarkers of therapeutic response., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)