OncoSNIPE® Study Protocol, a study of molecular profiles associated with development of resistance in solid cancer patients.

Background: Nowadays, evaluation of the efficacy and the duration of treatment, in context of monitoring patients with solid tumors, is based on the RECIST methodology. With these criteria, resistance and/or insensitivity are defined as tumor non-response which does not allow a good understanding of the diversity of the underlying mechanisms. The main objective of the OncoSNIPE® collaborative clinical research program is to identify early and late markers of resistance to treatment.

In-vivo metabolic characterization of healthy prostate and orthotopic prostate cancer in rats using proton magnetic resonance spectroscopy at 4.7 T.

Background: To assist the development of new anti-cancer drugs, it is important to identify biomarkers of treatment efficacy in the preclinical phases of drug development. In order to improve the predictivity of preclinical experiments, more realistic animal models are needed, for example, tumors xenografted directly on the prostate gland of rodents.

Purpose: To characterize the in-vivo metabolism of healthy rat prostate and of an orthotopic human prostate cancer model using proton magnetic resonance spectroscopy (MRS).

Assessment of multiparametric MRI in a human glioma model to monitor cytotoxic and anti-angiogenic drug effects.

Early imaging or blood biomarkers of tumor response is needed to customize anti-tumor therapy on an individual basis. This study evaluates the sensitivity and relevance of five potential MRI biomarkers. Sixty nude rats were implanted with human glioma cells (U-87 MG) and randomized into three groups: one group received an anti-angiogenic treatment (Sorafenib), a second a cytotoxic drug [1,3-bis(2-chloroethyl)-1-nitrosourea, BCNU (Carmustine)] and a third no treatment.

VEGF kinoid vaccine, a therapeutic approach against tumor angiogenesis and metastases.

Tumor growth depends on blood supply, requiring the development of new vessels, and vascular endothelial growth factor (VEGF) plays a central role in neoangiogenic processes. For this reason, VEGF represents a target for the development of new therapeutic antiangiogenic molecules. Clinical trials using anti-VEGF mAbs such as bevacizumab have validated the efficacy of this therapeutic approach but have also revealed adverse effects.

A virus-directed enzyme prodrug therapy (VDEPT) strategy for lung cancer using a CYP2B6/NADPH-cytochrome P450 reductase fusion protein.

Virus-directed enzyme prodrug therapy (VDEPT) is an emerging strategy against cancer. Our approach is a P450-based VDEPT that consists of using cyclophosphamide (CPA) as a prodrug and a Cytochrome P450 2B6/NADPH cytochrome P450 reductase fusion protein (CYP2B6/RED) as a prodrug-activating enzyme. Due to the heterogenous expression of proteins in tumor cells, basal reductase activity may not be sufficient to supply CYP2B6 with electrons, the fusion protein should enable the expression of both proteins at high levels in tumor cells.

Rationale supporting the use of vasoconstrictors for intraperitoneal chemotherapy with platinum derivatives.

By decreasing drug drainage through the peritoneal and tumoral vascular networks, epinephrine increases the penetration of cisplatin and oxaliplatin into the metastatic peritoneal tumor nodules. This improved drug penetration increases their antitumor efficacy, allowing the cure of millimetric-sized peritoneal tumor nodules that could not be obtained with cisplatin or oxaliplatin used alone. However, limited drug diffusion into supramillimetric nodules did not result in curing advanced peritoneal carcinomatosis, unless complete resection of macroscopic localized tumor nodules is performed before intraperitoneal chemotherapy.

Antitumor activity of troxacitabine (Troxatyl) against anthracycline-resistant human xenografts.

Purpose: We have recently identified a deoxycytidine nucleoside analogue, troxacitabine (beta- L-dioxolane cytidine, Troxatyl; Shire BioChem), which has potent antitumor activity against both leukemia and solid tumors. In contrast to the cytidine nucleoside analogues currently in clinical use (cytarabine and gemcitabine), troxacitabine is a poor substrate of nucleoside transporters and enters cells primarily by passive diffusion. This unusual property led us to evaluate the efficacy of troxacitabine in multidrug resistant (MDR) and multidrug resistance-associated protein (MRP) tumors.