Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase that regulates a plethora of downstream signaling pathways essential for cell migration, proliferation and death, processes that are exploited by cancer cells during malignant progression. These well-established tumorigenic activities, together with its high expression and activity in different cancer types, highlight FAK as an attractive target for cancer therapy. We have assessed and characterized the therapeutic potential and the biological effects of BI 853520, a novel small chemical inhibitor of FAK, in several preclinical mouse models of breast cancer. Treatment with BI 853520 elicits a significant reduction in primary tumor growth caused by an anti-proliferative activity by BI 853520. In contrast, BI 853520 exerts effects with varying degrees of robustness on the different stages of the metastatic cascade. Together, the data demonstrate that the repression of FAK activity by the specific FAK inhibitor BI 853520 offers a promising anti-proliferative approach for cancer therapy.

Background/ObjectivesGut hormones such as cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) play a role as satiation factors. Strategies to enhance satiation peptide secretion could provide a therapeutic approach for obesity. Carbohydrates and lipids have been extensively investigated in relation to peptide release. In contrast, the role of proteins or amino acids is less clear. Our aim was to compare the effects of the amino acids L-tryptophan (L-trp) and L-leucine (L-leu) separately on gastric emptying and gut peptide secretion.Participants/MethodsThe study was conducted as a randomized (balanced), double-blind, parallel-group trial. A total of 10 lean and 10 non-diabetic obese participants were included. Participants received intragastric loads of L-trp (0.52 g and 1.56 g) and L-leu (1.56 g), dissolved in 300 mL tap water; 75 g glucose and 300 mL tap water served as control treatments.ResultsResults of the study are: i) L-trp at the higher dose stimulates CCK release (p = 0.0018), and induces a significant retardation in gastric emptying (p = 0.0033); ii) L-trp at the higher dose induced a small increase in GLP-1 secretion (p = 0.0257); iii) neither of the amino acids modulated subjective appetite feelings; and iv) the two amino acids did not alter insulin or glucose concentrations.ConclusionsL-trp is a luminal regulator of CCK release with effects on gastric emptying, an effect that could be mediated by CCK. L-trp’s effect on GLP-1 secretion is only minor. At the doses given, the two amino acids did not affect subjective appetite feelings.Trial RegistrationClinicalTrials.gov NCT02563847

Purpose Our aim is to describe the role of immune checkpoint inhibitors (ICI) in clinical practice by providing the patient and tumor characteristics as well as survival and toxicity rates by sex. Methods We used electronic health records to identify patients treated at the Cancer Center of the University Hospital Bern, Switzerland between January 1, 2017 and June 16, 2021. Results We identified 5109 patients, 689 of whom (13.5%) received at least one dose of ICI. The fraction of patients who were prescribed ICI increased from 8.6% in 2017 to 22.9% in 2021. ICI represented 13.2% of the anticancer treatments in 2017 and increased to 28.2% in 2021. The majority of patients were male (68.7%), who were older than the female patients (median age 67 vs. 61 years). Over time, adjuvant and first line treatments increased for both sexes. Lung cancer and melanoma were the most common cancer types in males and females. The incidence of irAEs was higher among females (38.4% vs. 28.1%) and lead more often to treatment discontination in females than in males (21.1% vs. 16.8%). Independent of sex, the occurrence of irAEs was associated with greater median overall survival (OS, not reached vs. 1.1 years). Female patients had a longer median OS than males (1.9 vs. 1.5 years). Conclusions ICI play an increasingly important role in oncology. irAEs are more frequent in female patients and are associated with a longer OS. More research is needed to understand the association between patient sex and toxicity and survival.

Tumor-induced osteomalacia is a very rare paraneoplastic syndrome. It can be caused by phosphaturic mesenchymal tumor (PMT), a generally benign tumor that produces fibroblast growth factor 23 (FGF-23), which can cause a severe renal phosphate wasting syndrome. Upon complete surgical removal of the tumor, FGF-23 normalizes and the osteomalacia is cured. In cases in which surgery is not feasible, radiofrequency ablation (RFA) is the treatment of choice. We describe a case with a PMT situated in the sacrum, in close proximity to the sacral plexus. Both surgery and RFA were considered potentially nerve damaging. Since the tumor showed expression of somatostatin receptors, we opted for a peptide receptor radionuclide therapy (PRRT) with ¹⁷⁷Lu-DOTATOC. However, the therapy did not show the expected success, since the FGF-23 level had even temporarily increased. The patient was then successfully treated with RFA. A partial remission of the tumor was achieved and FGF-23 levels nearly normalized. Despite some severe neurological side effects, the patient showed a remarkable clinical improvement, with no symptoms of osteomalacia within a few weeks.