Fibroblast growth factor (FGF) signaling is essential for normal and cancer biology. Mammalian FGF family members participate in multiple signaling pathways by binding to heparan sulfate and FGF receptors (FGFR) with varying affinities. FGF2 is the prototype member of the FGF family and interacts with its receptor to mediate receptor dimerization, phosphorylation, and activation of signaling pathways, such as Ras-MAPK and PI3K pathways. Excessive mitogenic signaling through the FGF/FGFR axis may induce carcinogenic effects by promoting cancer progression and increasing the angiogenic potential, which can lead to metastatic tumor phenotypes. Dysregulated FGF/FGFR signaling is associated with aggressive cancer phenotypes, enhanced chemotherapy resistance and poor clinical outcomes. In vitro experimental settings have indicated that extracellular FGF2 affects proliferation, drug sensitivity, and apoptosis of cancer cells. Therapeutically targeting FGF2 and FGFR has been extensively assessed in multiple preclinical studies and numerous drugs and treatment options have been tested in clinical trials. Diagnostic assays are used to quantify FGF2, FGFRs, and downstream signaling molecules to better select a target patient population for higher efficacy of cancer therapies. This review focuses on the prognostic significance of FGF2 in cancer with emphasis on therapeutic intervention strategies for solid and hematological malignancies.

Syndecan-1 (SDC1, CD138) is a key cell surface adhesion molecule essential for maintaining cell morphology and interaction with the surrounding microenvironment. Deregulation of SDC1 contributes to cancer progression by promoting cell proliferation, metastasis, invasion and angiogenesis, and is associated with relapse through chemoresistance. SDC1 expression level is also associated with responses to chemotherapy and with prognosis in multiple solid and hematological cancers, including multiple myeloma and Hodgkin lymphoma. At the tissue level, the expression levels of SDC1 and the released extracellular domain of SDC1 correlate with tumor malignancy, phenotype, and metastatic potential for both solid and hematological tumors in a tissue-specific manner. The SDC1 expression profile varies among cancer types, but the differential expression signatures between normal and cancer cells in epithelial and stromal compartments are directly associated with aggressiveness of tumors and patient's clinical outcome and survival. Therefore, relevant biomarkers of SDC signaling may be useful for selecting patients that would most likely respond to a particular therapy at the time of diagnosis or perhaps for predicting relapse. In addition, the reciprocal expression signature of SDC between tumor epithelial and stromal compartments may have synergistic value for patient selection and the prediction of clinical outcome.

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BackgroundIbrutinib is a tyrosine kinase inhibitor most commonly associated with atrial fibrillation. However, additional cardiotoxicities have been identified, including accelerated hypertension. The incidence and risk factors of new or worsening hypertension following ibrutinib treatment are not as well known.MethodsWe conducted a retrospective study of 144 patients diagnosed with B cell malignancies treated with ibrutinib (n=93) versus conventional chemoimmunotherapy (n=51) and evaluated their effects on blood pressure at 1, 2, 3 and 6 months after treatment initiation. Descriptive statistics were used to compare baseline characteristics for each treatment group. Fisher’s exact test was used to identify covariates significantly associated with the development of hypertension. Repeated measures analyses were conducted to analyse longitudinal blood pressure changes.ResultsBoth treatments had similar prevalence of baseline hypertension at 63.4% and 66.7%, respectively. There were no differences between treatments by age, sex and baseline cardiac comorbidities. Both systolic and diastolic blood pressure significantly increased over time with ibrutinib compared with baseline, whereas conventional chemoimmunotherapy was not associated with significant changes in blood pressure. Baseline hypertensive status did not affect the degree of blood pressure change over time. A significant increase in systolic blood pressure (defined as more than 10 mm Hg) was noted for ibrutinib (36.6%) compared with conventional chemoimmunotherapy (7.9%) at 1 month after treatment initiation. Despite being hypertensive at follow-up, 61.2% of patients who were treated with ibrutinib did not receive adequate blood pressure management (increase or addition of blood pressure medications). Within the ibrutinib group, of patients who developed more than 20 mm Hg increase in systolic blood pressure, only 52.9% had hypertension management changes.ConclusionsIbrutinib is associated with the development of hypertension and worsening of blood pressure. Cardiologists and oncologists must be aware of this cardiotoxicity to allow timely management of blood pressure elevations.