Cancers

Methyladenosine modifications are the most abundant RNA modifications, including N6-methyladenosine (m6A), N1-methyladenosine (m1A), and 2’-O-methyladenosine (m6Am). As reversible epigenetic modifications, methyladenosine modifications in eukaryotic RNAs are not invariable. Drastic alterations of m6A are found in a variety of diseases, including cancers. Dynamic changes of m6A modification induced by abnormal methyltransferase, demethylases, and readers can regulate cancer progression via interfering with the splicing, localization, translation, and stability of mRNAs. Meanwhile, m6A, m1A, and m6Am modifications also exert regulatory effects on noncoding RNAs in cancer progression. In this paper, we reviewed recent findings concerning the underlying biomechanism of methyladenosine modifications in oncogenesis and metastasis and discussed the therapeutic potential of methyladenosine modifications in cancer treatments.

Predicting responses to immune checkpoint blockade (ICB) lacks official standards despite the discovery of several markers. Expensive drugs and different reactivities for each patient are the main disadvantages of immunotherapy. Gastric cancer is refractory and stem-like in nature and does not respond to immunotherapy. In this study, we aimed to identify a characteristic gene that predicts ICB response in gastric cancer and discover a drug target for non-responders. We built and evaluated a model using four machine learning algorithms for two cohorts of bulk and single-cell RNA seq to predict ICB response in gastric cancer patients. Through the LASSO feature selection, we discovered a marker gene signature that distinguishes responders from non-responders. VCAN, a candidate characteristic gene selected by all four machine learning algorithms, had a significantly high prevalence in non-responders (p = 0.0019) and showed a poor prognosis (p = 0.0014) at high expression values. This is the first study to discover a signature gene for predicting ICB response in gastric cancer by molecular subtype and provides broad insights into the treatment of stem-like immuno-oncology through precision medicine.

Considering the rapid improvement of cancer drugs’ efficacy and the discovery of new molecular targets, the formulation of therapeutical indications based on the multidisciplinary approach of MTB is becoming increasingly important for attributing the correct salience to the targets identified in a single patient. Nevertheless, one of the biggest stumbling blocks faced by MTBs is not the bare indication, but its implementation in the clinical practice. Indeed, administering the drug suggested by MTB deals with some relevant difficulties: the economical affordability and geographical accessibility represent some of the major limits in the patient’s view, while bureaucracy and regulatory procedures are often a disincentive for the physicians. In this review, we explore the current literature reporting MTB experiences and precision medicine clinical trials, focusing on the challenges that authors face in applying their therapeutical indications. Furthermore, we analyze and discuss some of the solutions devised to overcome these difficulties to support the MTBs in finding the most suitable solution for their specific situation. In conclusion, we strongly encourage regulatory agencies and pharmaceutical companies to develop effective strategies with medical centers implementing MTBs to facilitate access to innovative drugs and thereby allow broader therapeutical opportunities to patients.

Preoperative grade prediction is important in diagnostics of glioma. Even more important can be follow-up after chemotherapy and radiotherapy of high grade gliomas. In this review we provide an overview of MR-spectroscopy (MRS), technical aspects, and different clinical scenarios in the diagnostics and follow-up of gliomas in pediatric and adult populations. Furthermore, we provide a recap of the current research utility and possible future strategies regarding proton- and phosphorous-MRS in glioma research.

The combination of atezolizumab and bevacizumab (A + B) is the new standard of care for the systemic first-line treatment of hepatocellular carcinoma (HCC). However, up to now there are only few data on the safety and efficacy of A + B in real life. We included patients with advanced HCC treated with A + B as first-line therapy at four cancer centers in Germany and Austria between December 2018 and August 2021. Demographics, overall survival (OS), and adverse events were assessed until 15 September 2021. We included 66 patients. Most patients had compensated cirrhosis (n = 34; 52%), while Child–Pugh class B cirrhosis was observed in 23 patients (35%), and class C cirrhosis in 5 patients (8%). The best responses included a complete response (CR) in 7 patients (11%), a partial response (PR) in 12 patients (18%), stable disease (SD) in 22 patients (33%), and progressive disease in 11 patients (17%). The median progression-free (PFS) survival was 6.5 months, while the median overall survival (OS) was not reached in this cohort (6-month OS: 69%, 12-month OS: 60%, 18-month OS: 58%). Patients with viral hepatitis seemed to have a better prognosis than patients with HCC of non-viral etiology. The real-world PFS and OS were comparable to those of the pivotal IMBRAVE trial, despite including patients with worse liver function in this study. We conclude that A + B is also highly effective in a real-life setting, with manageable toxicity, especially in patients with compensated liver disease. In patients with compromised liver function (Child B and C), the treatment showed low efficacy and, therefore, it should be well considered before administration to these patients.

From a public health perspective, cancer is a major issue, and it contributes to a high economic and societal burden. Lifestyle-associated risk factors play a crucial role in cancer prevention. The present narrative review aims to summarize the existing evidence on the relationship of physical activity and sedentary behavior to cancer survival, including the evidence on mortality and other health-related outcomes. There is strong evidence that physical activity before, during, and after cancer diagnosis improves outcomes for breast and colorectal cancers. In addition, there is emerging evidence that reduced levels of sedentary behavior in cancer survivors are associated with improved outcomes. Future studies are needed to strengthen the evidence and to provide details on additional cancer sites. In the meantime, existing recommendations for physical activity and sedentary behavior in cancer survivors should be followed to improve the health status of cancer survivors.

Hematopoietic stem cells (HSCs) are rare, self-renewing cells that perch on top of the hematopoietic tree. The HSCs ensure the constant supply of mature blood cells in a tightly regulated process producing peripheral blood cells. Intense efforts are ongoing to optimize HSC engraftment as therapeutic strategy to treat patients suffering from hematopoietic diseases. Preclinical research paves the way by developing methods to maintain, manipulate and expand HSCs ex vivo to understand their regulation and molecular make-up. The generation of a sufficient number of transplantable HSCs is the Holy Grail for clinical therapy. Leukemia stem cells (LSCs) are characterized by their acquired stem cell characteristics and are responsible for disease initiation, progression, and relapse. We summarize efforts, that have been undertaken to increase the number of long-term (LT)-HSCs and to prevent differentiation towards committed progenitors in ex vivo culture. We provide an overview and compare methods currently available to isolate, maintain and enrich HSC subsets, progenitors and LSCs and discuss their individual advantages and drawbacks.

Laryngeal squamous cell cancer (LSCC) accounts for almost 25–30% of all head and neck squamous cell cancers and is clustered according to the affected districts, as this determines distinct tendency to recur and metastasize. A major role for numerous genetic alterations in driving the onset and progression of this neoplasm is emerging. However, major efforts are still required for the identification of molecular markers useful for both early diagnosis and prognostic definition of LSCC that is still characterized by significant morbidity and mortality. Non-coding RNAs appear the most promising as they circulate in all the biological fluids allowing liquid biopsy determination, as well as due to their quick and characteristic modulation useful for non-invasive detection and monitoring of cancer. Other critical aspects are related to recent progress in circulating tumor cells and DNA detection, in metastatic status and chemo-refractoriness prediction, and in the functional interaction of LSCC with chronic inflammation and innate immunity. We review all these aspects taking into account the progress of the technologies in the field of next generation sequencing.

The aim of this study was to assess the associations of dietary fat intake with BC occurrence and dietary patterns. This case-control study involved 420 women aged 40–79 years from northeastern Poland, including 190 newly diagnosed BC cases. Dietary data were collected using a food frequency questionnaire (62-item FFQ-6®). The Quick Food Scan of the National Cancer Institute and the Percentage Energy from Fat Screener scoring procedures were used to estimate the percentage energy from dietary fat (Pfat). The odds of BC occurrence was three times higher in the Pfat > 32%. The Pfat > 32% was positively associated with the ‘Non-Healthy’ DP and inversely associated with the Polish-aMED® score, ‘Prudent’ DP, and ‘Margarine and Sweetened Dairy’ DP. This case-control study suggests that a higher dietary fat intake (>32%) may contribute to an increased occurrence of peri- and postmenopausal breast cancer in women. Given the obtained results, an unhealthy dietary pattern characterized by the consumption of highly processed, high in sugar foods and animal fat foods should be avoided to reduce fat intake. Instead, the frequent consumption of low-processed plant foods, fish, and moderate consumption of low-fat dairy should be recommended since this pro-healthy diet is inversely associated with dietary fat intake.

Metastasectomy and/or local ablative therapy in metastatic colorectal cancer (mCRC) patients often provide long-term survival. Health-related quality of life (HRQoL) data in curatively treated mCRC are limited. In the RAXO-study that evaluated repeated resectability, a multi-cross-sectional HRQoL substudy with 15D, EQ-5D-3L, QLQ-C30, and QLQ-CR29 questionnaires was conducted. Mean values of patients in different treatment groups were compared with age- and gender-standardized general Finnish populations. The questionnaire completion rate was 444/477 patients (93%, 1751 questionnaires). Mean HRQoL was 0.89–0.91 with the 15D, 0.85–0.87 with the EQ-5D, 68–80 with the EQ-5D-VAS, and 68–79 for global health status during curative treatment phases, with improvements in the remission phase (disease-free >18 months). In the remission phase, mean EQ-5D and 15D scores were similar to the general population. HRQoL remained stable during first- to later-line treatments, when the aim was no longer cure, and declined notably when tumour-controlling therapy was no longer meaningful. The symptom burden affecting mCRC survivors’ well-being included insomnia, impotence, urinary frequency, and fatigue. Symptom burden was lower after treatment and slightly higher, though stable, through all phases of systemic therapy. HRQoL was high in curative treatment phases, further emphasizing the strategy of metastasectomy in mCRC when clinically meaningful.