Author: RR

Oncofetal Gene SALL4 in Aggressive Hepatocellular Carcinoma

RR

SUMMARY:Hepatocellular Carcinoma (HCC) originates from hepatocytes and is the sixth most common cancer and third leading cause of cancer related death worldwide. Chronic liver injury and cirrhosis have been implicated as important risk factors. This may result from infections with Hepatitis B and C, heavy alcohol consumption, exposure to Aflatoxin, a potent carcinogen produced by Aspergillus species and non alcoholic fatty liver disease (NAFLD) seen in patients with obesity and diabetes. The underlying liver disease contributing to tumorigenesis adds to the molecular complexity of HCC. The standard intervention for advanced stage HCC has been multi receptor Tyrosine Kinase Inhibitor, NEXAVAR® (Sorafenib). Alpha Feto Protein (AFP) is normally produced by the liver and yolk sac of a fetus during pregnancy and decreases soon after birth. AFP has been used as a serological test for HCC surveillance. In this study, the authors evaluated the role of SALL4, an oncofetal gene, which is expressed in the fetal liver but silenced in the adult liver. In HCC, SALL4 is re-expressed in the tumor tissue and may play an important role in hepatocarcinogenesis and may also portend poor outcomes. SALL4 may therefore serve as an important biomarker and molecular target. Targeting SALL4 could increase the expression of tumor suppressor gene PTEN and block the PI3K survival signaling pathway, by dephosphorylating AKT. The authors concluded that testing hepatic tumor tissue for SALL4 at the time of diagnosis may have prognostic value and may identify patient groups who are likely to benefit from SALL4 targeted therapy. Yong KJ, Gao C, Lim J, et al. N Engl J Med 2013; 368:2266-2276

 

 

REVLIMID® (Lenalidomide)

RR

The FDA on June 5, 2013 approved REVLIMID® capsules for the treatment of patients with mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one of which included VELCADE® (Bortezomib). REVLIMID® is a product of Celgene Corporation.

XGEVA® (Denosumab)

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XGEVA® (Denosumab): The FDA on June 13, 2013 approved the use of XGEVA® subcutaneous injection, for the treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity. XGEVA® is a product of Amgen Inc.

Advanced Melanoma – Bringing Bench Research to the Patient’s Bedside

RR

Lambrolizumab (MK-3475) is a humanized anti–PD-1 monoclonal antibody that has demonstrated significant benefit for those patients with advanced Malignant Melanoma regardless of their prior therapy with anti-CTLA 4 antibody, YERVOY® (Ipilimumab). The programmed death 1 (PD-1) receptor is an inhibitory receptor expressed on activated T-cells in the tumor micro environment. The anti–PD-1 antibody by blocking the PD-1 receptor essentially unleashes the immune system to fight off cancer cells. This information published in the NEJM in June 2013 and presented at the 2013 ASCO annual meeting gives an additional option for patients with advanced Malignant Melanoma.

MEKINIST® (Trametinib)

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MEKINIST® (Trametinib): The FDA on May 29, 2013 approved the use of MEKINIST® tablet for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutation, as detected by an FDA-approved test. The FDA also approved the THxID BRAF assay (bioMerieux, Inc.) for detection of BRAF V600E and V600K mutations. MEKINIST® is not indicated for treatment of patients who had received prior BRAF inhibitor therapy. MEKINIST® is a product of GlaxoSmithKline, LLC.

TAFINLAR® (Dabrafenib)

RR

TAFINLAR® (Dabrafenib): The FDA on May 29, 2013 approved the use of TAFINLAR® capsule for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test. TAFINLAR® is not indicated for the treatment of patients with wild-type BRAF melanoma because of the potential risk of tumor proliferation. The FDA also approved the THxID BRAF assay (bioMerieux, Inc.) for detection of BRAF V600E mutations. TAFINLAR® is a product of GlaxoSmithKline, LLC.

XOFIGO® (Radium Ra 223 dichloride)

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XOFIGO® (Radium Ra 223 dichloride): The FDA on May 15, 2013 approved XOFIGO® Injection for the treatment of castration-resistant prostate cancer patients with symptomatic bone metastases and no known visceral metastatic disease. XOFIGO® is an alpha-particle emitting radiotherapeutic drug. It mimics calcium and forms complexes with hydroxyapatite at sites of increased bone turnover, as seen at metastatic lesions in the bone. XOFIGO® is a product of Bayer HealthCare Pharmaceuticals Inc.

TARCEVA® (Erlotinib)

RR

TARCEVA® (Erlotinib): The FDA on May 14, 2013 approved TARCEVA® for the first-line treatment of metastatic non-small cell lung cancer (NSCLC) patients whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations. The FDA concurrently approved the cobas EGFR Mutation Test, a companion diagnostic test for detection of these molecular abnormalities. TARCEVA has had prior FDA approval for the treatment of patients with locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen and for maintenance treatment of patients with locally advanced or metastatic NSCLC, whose disease has not progressed after four cycles of platinum-based first-line chemotherapy. TARCEVA® is a product of Astellas Pharma Inc.

MYELOMA – mSMART is the way to go

RR

Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) developed by the Mayo Clinic, unlike the present staging systems takes cytogenetic features into consideration and stratifies patients into High risk, Intermediate risk and Low risk groups. The clinician, based on the risk, then decides on the most appropriate therapy. This Risk-Adapted Therapy should result in better outcomes without compromising care. The 2013 mSMART Consensus Guidelines were published in the April issue of the Mayo Clinic Proceedings.