Preemptive tumor profiling for biomarker-stratified early clinical drug development in metastatic breast cancer patients.

Biomarker-stratified cancer pharmacotherapy was pioneered in the care of breast cancer patients. The utility of agents modulating hormone receptors, synthesis of steroid hormones, or HER2-targeting agents has been greatly enhanced by the detection of predictive biomarkers in diagnostic tumor samples. Based on deeper understanding of breast cancer biology multiple drug candidates have been developed to modulate additional molecular targets which may associate with specific biomarker profiles.

Bone turnover markers as predictive tools for skeletal complications in men with metastatic prostate cancer treated with zoledronic acid.

Background: Bone turnover markers are helpful to diagnose bone metastases. The aim of this study was to evaluate the usefulness of these markers in prostate cancer patients with bone metastases before and during the treatment with zoledronic acid as predictive and monitoring tools of skeletal-related events (SRE).

Methods: One hundred seventeen prostate cancer patients with bone metastases and treated with zoledronic acid (4 mg every 4 weeks) were examined.

The dual EGF/VEGF receptor tyrosine kinase inhibitor AEE788 inhibits growth of human hepatocellular carcinoma xenografts in nude mice.

We investigated the effect of AEE788, a novel dual receptor tyrosine kinase inhibitor of the EGF and the VEGF receptor, for treatment of human HCC cell lines and in a subcutaneous xenograft model. Cell viability and apoptosis of HepG2 and Hep3B cells incubated with 0.1-100 microM AEE788 were quantified.

Rapid and sustained influence of intravenous zoledronic Acid on course of pain and analgesics consumption in patients with cancer with bone metastases: a multicenter open-label study over 1 year.

Background: Bone metastases might lead to severe bone pain, pathologic fractures, and hypercalcemia. Osteolytic destruction is caused by the activation of osteoclasts by release of tumor-derived stimulating factors. Bisphosphonates are known to inhibit osteoclast function and, therefore, to alleviate the adverse effects of tumor-induced bone resorption.

Serial markers of bone turnover in men with metastatic prostate cancer treated with zoledronic Acid for detection of bone metastases progression.

Objectives: This study assessed the usefulness of serial measurements of bone turnover markers in men with metastatic prostate cancer treated with zoledronic acid to detect disease progression.

Methods: Serum measurements of total alkaline phosphatase (tALP), bone-specific alkaline phosphatase (bALP), cross-linked N-terminal (NTx) and cross-linked C-terminal (CTx) telopeptides of type I collagen, amino-terminal procollagen propeptides of type I collagen (PINP), C-terminal telopeptides of type I collagen (ICTP), and prostate-specific antigen (PSA) were performed in 77 prostate cancer patients suffering from bone metastases and treated with zoledronic acid up to 15 mo. Fifty patients were with and 27 patients without objective evidence of metastatic bone progression during the administration of zoledronic acid.

Effects of a combined treatment with mTOR inhibitor RAD001 and tamoxifen in vitro on growth and apoptosis of human cancer cells.

Objective: Interactions between estrogen receptor signaling and the PI3K/Akt pathway are present in estrogen-dependent cancer cells. Therapeutical inhibition of each of these pathways has been proven to exert antitumoral effects. Inhibition of mammalian target of rapamycin (mTOR), a downstream target of Akt, is able to restore tamoxifen response in tamoxifen-resistant breast cancer cells.

Sustained complete molecular remissions after treatment with imatinib-mesylate in patients with failure after allogeneic stem cell transplantation for chronic myelogenous leukemia: results of a prospective phase II open-label multicenter study.

Purpose: In the era of molecular therapy of chronic myelogenous leukemia (CML) applying BCR-ABL tyrosine kinase inhibitors, the usefulness of molecular end points, in particular, quantitative polymerase chain reaction (PCR) for BCR-ABL in monitoring responses has been broadly accepted. Therefore, we have designed a prospective phase II trial in CML, which, for the first time, evaluated the feasibility and safety of molecular end points as surrogate markers to guide through a stratified treatment algorithm within a multicenter trial.

Patients And Methods: As a clinical model, we adopted minimal residual disease (MRD) found in relapse after allogeneic stem cell transplantation (SCT) in CML.

Pre-therapeutic dosimetry and biodistribution of 86Y-DOTA-Phe1-Tyr3-octreotide versus 111In-pentetreotide in patients with advanced neuroendocrine tumours.

Purpose: For the internal radiotherapy of neuroendocrine tumours, the somatostatin analogue DOTATOC labelled with 90Y is frequently used [90Y-DOTA-Phe1-Tyr3)-octreotide (SMT487-OctreoTher)]. Radiation exposure to the kidneys is critical in this therapy as it may result in renal failure. The aim of this study was to compare cumulative organ and tumour doses based upon dosimetric data acquired with the chemically identical 86Y-DOTA-Phe1-Tyr3-octreotide (considered as the gold standard) and the commercially available 111In-pentetreotide.