Metformin, one of most widely prescribed oral hypoglycemic agents, has recently received increased attention because of its potential antitumorigenic effects that are thought to be independent of its hypoglycemic effects. Several potential mechanisms have been suggested for the ability of metformin to suppress cancer growth in vitro and vivo: (1) activation of LKB1/AMPK pathway, (2) induction of cell cycle arrest and/or apoptosis, (3) inhibition of protein synthesis, (4) reduction in circulating insulin levels, (5) inhibition of the unfolded protein response (UPR), (6) activation of the immune system, and (7) eradication of cancer stem cells. There is also a growing number of evidence, mostly in the form of retrospective clinical studies that suggest that metformin may be associated with a decreased risk of developing cancer and with a better response to chemotherapy. There are currently several ongoing randomized clinical trials that incorporate metformin as an adjuvant to classic chemotherapy and aim to evaluate its potential benefits in this setting. This review highlights basic aspects of the molecular biology of metformin and summarizes new advances in basic science as well as intriguing results from recent clinical studies.

Key Points Significant improvement in outcome is a reality for newly diagnosed AL amyloidosis in the past decade. Six-month mortality among transplant ineligible patients has declined since 2005.

In 2014, the International Myeloma Working Group reclassified patients with smoldering multiple myeloma (SMM) and bone marrow-plasma cell percentage (BMPC%) ≥ 60%, or serum free light chain ratio (FLCr) ≥ 100 or >1 focal lesion on magnetic resonance imaging as multiple myeloma (MM). Predictors of progression in patients currently classified as SMM are not known. We identified 421 patients with SMM, diagnosed between 2003 and 2015. The median time to progression (TTP) was 57 months (CI, 45–72). BMPC% > 20% [hazard ratio (HR): 2.28 (CI, 1.63–3.20); p < 0.0001]; M-protein > 2g/dL [HR: 1.56 (CI, 1.11–2.20); p = 0.01], and FLCr > 20 [HR: 2.13 (CI, 1.55–2.93); p < 0.0001] independently predicted shorter TTP in multivariate analysis. Age and immunoparesis were not significant. We stratified patients into three groups: low risk (none of the three risk factors; n = 143); intermediate risk (one of the three risk factors; n = 121); and high risk (≥2 of the three risk factors; n = 153). The median TTP for low-, intermediate-, and high-risk groups were 110, 68, and 29 months, respectively (p < 0.0001). BMPC% > 20%, M-protein > 2 g/dL, and FLCr > 20 at diagnosis can be used to risk stratify patients with SMM. Patients with high-risk SMM need close follow-up and are candidates for clinical trials aiming to prevent progression.

Objectives Lung cancer is strongly associated with venous thromboembolism (VTE), but primary prevention against VTE is not a validated management strategy. Risk assessment models will be necessary for efficient implementation of preventative strategies. Materials and methods Utilizing a prospectively collected lung cancer database, we aimed to validate the Khorana Risk Score (KRS) in the prediction of VTE among patients with lung cancer. VTE events were retrospectively identified by reviewers unaware of the clinical prediction score calculation. The association between KRS and the risk of VTE was examined using cumulative incidence function with competing risks models. Mortality prediction was evaluated as secondary outcome. Results We included 719 patients in our review. The patients were predominantly older males with NSCLC and 40% had metastatic disease at inception. The median follow up was 15.2 months. There were 83 VTEs (11.5%) and 568 (78.8%) patients died. A high KRS (Cumulative Incidence 12.4%, 95% Confidence Interval 6.4-20.5%) was not associated with VTE compared to an intermediate score (Cumulative Incidence 12.1%, 95% Confidence Interval 9.5-15.0%)) in both univariate and multivariable analyses. However, a high KRS was a predictor of mortality (HR 1.7 95% CI 1.4 - 2.2). Conclusions Among patients with lung cancer the KRS did not stratify the patients at the highest risk of VTE. Improved risk stratification methods are needed for this group of patients prior to implementing a primary prevention strategy.