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The PI3K/AKT/mTOR (PAM) signaling pathway is a highly conserved signal transduction network in eukaryotic cells that promotes cell survival, cell growth, and cell cycle progression. Growth factor signalling to transcription factors in the PAM axis is highly regulated by multiple cross-interactions with several other signaling pathways, and dysregulation of signal transduction can predispose to cancer development. The PAM axis is the most frequently activated signaling pathway in human cancer and is often implicated in resistance to anticancer therapies. Dysfunction of components of this pathway such as hyperactivity of PI3K, loss of function of PTEN, and gain-of-function of AKT, are notorious drivers of treatment resistance and disease progression in cancer. In this review we highlight the major dysregulations in the PAM signaling pathway in cancer, and discuss the results of PI3K, AKT and mTOR inhibitors as monotherapy and in co-administation with other antineoplastic agents in clinical trials as a strategy for overcoming treatment resistance. Finally, the major mechanisms of resistance to PAM signaling targeted therapies, including PAM signaling in immunology and immunotherapies are also discussed.

Background: Recommendations for surveillance imaging for resected melanoma vary considerably. This study examined the utility of imaging in patients with a high‐risk primary melanoma undergoing a protocolized imaging schedule. Methods: This retrospective study involved data collection regarding imaging, recurrence, and outcome characteristics for patients referred to the Victorian Melanoma Service from January 2016–April 2020 and managed for resected stage IIC or III melanoma. Patients with a T4b tumor who did not undergo a sentinel lymph node biopsy were included (T4bNX). Recurrences were "clinically detected" if they were primarily detected by patient symptoms or physical examination, or 'imaging‐detected' if the patient was asymptomatic. Cox regression models including time‐varying co‐variates were used to assess the impact of imaging‐detected versus clinically‐detected recurrence on overall survival. Results: Over a median follow‐up time of 2.7 years, 199 patients underwent surveillance imaging (T4bNX:22, IIC:33, IIIA:22, IIIB:60, IIIC:61, IIID:1), and 44% (n = 88) experienced disease recurrence. Imaging detected over half (53%) of all recurrences. In adjusted analyses, mortality risk was reduced after an imaging‐detected compared to clinically‐detected recurrence at any given time from the start of surveillance (hazard ratio 0.25, 95% confidence interval 0.10–0.66, p =.005). Conclusion: Our study indicates that routine imaging in the early follow‐up period of resected T4bNX, stage IIC and III melanoma plays an important role in the detection of asymptomatic recurrences. Imaging‐detected recurrence may be associated with a survival benefit and studies with more prolonged follow‐up are required to confirm these findings. [ABSTRACT FROM AUTHOR]

Cucurbitacins constitute a group of cucumber-derived dietary lipids, highly oxidized tetracyclic triterpenoids, with potential medical uses. These compounds are known to interact with a variety of recognized cellular targets to impede the growth of cancer cells. Accumulating evidence has suggested that inhibition of tumor cell growth via induction of apoptosis, cell-cycle arrest, anti-metastasis and anti-angiogenesis are major promising chemo-preventive actions of cucurbitacins. Cucurbitacins may be a potential choice for investigations of synergism with other drugs to reverse cancer cells' treatment resistance. The detailed molecular mechanisms underlying these effects include interactions between cucurbitacins and numerous cellular targets (Bcl-2/Bax, caspases, STAT3, cyclins, NF-κB, COX-2, MMP-9, VEGF/R, etc.) as well as control of a variety of intracellular signal transduction pathways. The current study is focused on the efforts undertaken to find possible molecular targets for cucurbitacins in suppressing diverse malignant processes. The review is distinctive since it presents all potential molecular targets of cucurbitacins in cancer on one common podium. [ABSTRACT FROM AUTHOR]

Youth with a migration background are underserved by sexual healthcare. Insight in their experiences is essential to develop tailored services and counter disparities. We explored how youth with a migration background access sexual health information, experience public sexual healthcare, and navigate sexual health in their particular sociocultural contexts. We carried out nine semi-structured interviews and one group interview with twelve young people (18–24) with a migration background in Amsterdam, the Netherlands. Respondents were heterosexually oriented and of various sociocultural backgrounds. Data were analysed using thematic content analysis. Three themes emerged: 'Access to sexual health information', 'Access to primary sexual health care', and 'Strategies for sexual self-care'. Youth sought out information online or from peers, however, conversations mostly focussed on pleasure while risk was often not discussed. Youth valued anonymity when accessing sexual healthcare, and used several strategies, such as staying silent or adhering to values such as 'self-respect', to navigate sexual health within their everyday gendered environments. While these strategies manifested as sources of empowerment, they also resulted in potential vulnerabilities. To counter sexual health disparities among youth with a migration background, public sexual health services should provide culturally safe care and foster participatory collaborations with local stakeholders. [ABSTRACT FROM AUTHOR]

Summary: 18F‐FDG PET/CT scanning is routinely performed to stage and evaluate the treatment response in many malignancies. Immunotherapy is a rapidly growing treatment option for many cancers, and both clinicians and imaging specialists need to be familiar with 18F‐FDG PET/CT imaging characteristics unique to patients on this type of treatment. In particular, many immune‐related adverse events (irAEs) can be detected on 18F‐FDG PET/CT and early accurate identification is critical to reduce treatment related morbidity and incorrect interpretation of malignant disease status. This pictorial essay reviews frequently encountered irAEs in clinical practice and their appearances on 18F‐FDG PET/CT along with a brief discussion on pseudoprogression and hyperprogression. [ABSTRACT FROM AUTHOR]