1stOncology™: Cancer Intelligence Service – Page 17179 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Cytoreductive Surgery and Peritonectomy Procedures.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has become widely accepted as an effective method of treating peritoneal metastases (PM) from various cancers. CRS performed with the goal of removing all the macroscopic disease and comprises of peritonectomy procedures and visceral resections. CRS is a technically challenging surgery that requires a considerable amount of skill and appropriate patient selection. This article is a review of the techniques and current recommendations for performing CRS.

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Peritoneal Metastases: Prevention and Treatment.

Colorectal cancer is a surgicaly curable disease. It requires multimodality of treatment in Localy advanced and metastatic disease. Molecular markers like RAS mutation has brought in change in the mangement of metastatic disease. Nearly 15 to 20 % presents with peritonieal surface metastasis. The debate continues with systomic vs Cyutoreductive surgery with are without HIPEC. This article highlights management of peritoneal metastasis with special reference to prevention and treatment.

Randomized phase III trial of amrubicin/cisplatin versus etoposide/cisplatin as first-line treatment for extensive small-cell lung cancer.

Extensive-disease small-cell lung cancer (ED-SCLC) is characterized by rapid progression and relapse, despite high initial response rates to chemotherapy. The primary objective of this trial was to demonstrate the non-inferiority of amrubicin and cisplatin (AP) combination therapy compared with the standard first-line regimen of etoposide and cisplatin (EP) for previously untreated ED-SCLC in a Chinese population. When non-inferiority was verified, the objective was switched from non-inferiority to superiority.
From June 2008 to July 2010, 300 patients were enrolled and randomly assigned at a 1:1 ratio to AP and EP groups. AP-treated patients received cisplatin (60 mg/m(2), day 1) and amrubicin (40 mg/m(2), days 1-3) once every 21 days. EP-treated patients received cisplatin (80 mg/m(2), day 1) and etoposide (100 mg/m(2), days 1-3) once every 21 days. Treatment was continued for four to six cycles, except in cases of progressive disease or toxicity, and patient refusal.
Median overall survival (OS) for AP vs. EP treatment was 11.8 vs. 10.3 months (p = 0.08), respectively, demonstrating non-inferiority of AP to EP (AP group: 95 % confidence interval for hazard ratio 0.63-1.03 months). Median progression-free survival and overall response rates for AP vs. EP groups were 6.8 vs. 5.7 months (p = 0.35) and 69.8 % vs. 57.3 %, respectively. Drug-related adverse events in both groups were similar, with neutropenia being the most frequent (AP 54.4 %; EP 44.0 %). Leukopenia, pyrexia, and fatigue were more prevalent in the AP group, but all were clinically reversible and manageable.
AP therapy demonstrated non-inferiority to EP therapy, prolonging OS for 1.5 months, but this difference was not statistically significant; thus we propose AP as a promising treatment option for ED-SCLC in China.
This trial was registered on 10 April 2008 (ClinicalTrials.gov NCT00660504 ).

Shift of microRNA profile upon orthotopic xenografting of glioblastoma spheroid cultures.

Glioblastomas always recur despite surgery, radiotherapy and chemotherapy. A key player in the therapeutic resistance may be immature tumor cells with stem-like properties (TSCs) escaping conventional treatment. A group of promising molecular targets are microRNAs (miRs). miRs are small non-coding RNAs exerting post-transcriptional regulation of gene expression. In this study we aimed to identify over-expressed TSC-related miRs potentially amenable for therapeutic targeting. We used non-differentiated glioblastoma spheroid cultures (GSCs) containing TSCs and compared these to xenografts using a NanoString nCounter platform. This revealed 19 over-expressed miRs in the non-differentiated GSCs. Additionally, non-differentiated GSCs were compared to neural stem cells (NSCs) using a microarray platform. This revealed four significantly over-expressed miRs in the non-differentiated GSCs in comparison to the NSCs. The three most over-expressed miRs in the non-differentiated GSCs compared to xenografts were miR-126, -137 and -128. KEGG pathway analysis suggested the main biological function of these over-expressed miRs to be cell-cycle arrest and diminished proliferation. To functionally validate the profiling results suggesting association of these miRs with stem-like properties, experimental over-expression of miR-128 was performed. A consecutive limiting dilution assay confirmed a significantly elevated spheroid formation in the miR-128 over-expressing cells. This may provide potential therapeutic targets for anti-miRs to identify novel treatment options for GBM patients.

Rigel Announces Presentations at Upcoming American Association of Cancer Research (AACR) Conference

On April 12, 2016 Rigel Pharmaceuticals, Inc. (Nasdaq:RIGL) reported that it will present three scientific posters at the American Association of Cancer Research meeting in New Orleans, Louisiana from April 16 – 20, 2016 (Press release, Rigel, APR 12, 2016, View Source;p=RssLanding&cat=news&id=2156237 [SID:1234510707]). The posters will provide data from the company’s preclinical research projects focused on the important oncology and immuno-oncology targets, IRAK, AMPK and MerTK. Rigel plans to partner select preclinical research programs in the future.

An overview of each project and the corresponding AACR (Free AACR Whitepaper) presentation information follows:

IRAK
Rigel has an active IRAK preclinical research program aimed at understanding the role that certain inflammatory signals play in creating malignant changes in cells. IRAKs are key components in the signal transduction pathways associated with inflammation in humans. The company’s researchers have identified a family of IRAK4 inhibitors that are potent regulators of the inflammatory signal and are being evaluated for their potential utility in treating hematological cancers.

Abstract #: 346
Presentation Title: Potential role for R191, potent and selective IRAK4 kinase inhibitor, in treatment of hematological malignancies
Presentation Date: Sunday, April 17, 1:00pm – 5:00pm
Location: Section 17
Poster Board #: 2

AMPK
AMPK is a master regulator of cellular energy homeostasis and is an attractive research subject for its role in the metabolism of certain cancers, and other human diseases. Rigel has identified several potent direct AMPK activators, and is evaluating their potential to selectively activate AMPK within certain cancer cells to make them susceptible to the destructive properties of chemotherapeutic agents.

Abstract #: 3021
Presentation Title: Development of small molecule direct AMPK activators for the treatment of cancer
Presentation Time: Tuesday, April 19, 8:00am – 12:00pm
Location: Section 17
Poster Board #: 11

MerTK
Mer is a member of the TAM kinase family (Tyro3, AXL, Mer) known to provide tumor survival signals and support immunosuppressive tumor microenvironments. Rigel’s research on this family of receptor tyrosine kinases, also produced the AXL kinase inhibitor (R428/BGB324) currently in Phase 1 oncology studies with partner BerGenBio. The subject of the AACR (Free AACR Whitepaper) presentation is the company’s work with proprietary, orally delivered small molecules that block MerTK activity in vivo.

Abstract #: 4869
Presentation Title: Small molecule inhibitors of the anti-inflammatory TAM receptor MerTK
Presentation Time: Wednesday, April 20, 8:00am – 12:00pm
Location: Section 22
Poster Board #: 10