Here are just a few editorial highlights from the DDNews Cancer Research News site and other online vehicles of DDNews magazine to get you acquainted with the website and show you the range of our coverage.
Guest Commentary: Targeted payload therapies using radioimmunotherapy hit the right marks
By Dr. Dragan Cicic, Actinium Pharmaceuticals Inc.
Patients with blood cancers often face poor long-term survival outcomes, but a new treatment approach could offer more effective targeting of cancer cells as well as lower toxicity.
By Kelsey Kaustinen, DDNews Senior Editor
If all milestones are met, the agreement could be worth up to $817 million
By Jeffrey Bouley, DDNews Chief Editor
Multiple Myeloma Research Foundation announces six new clinical trials in 2014, and Cellectar Biosciences announces IND for relapsed or refractory multiple myeloma drug
By Lloyd Dunlap, DDNews Managing EditorService center will allow the expansion of new immunotherapy experimental platforms to advance translational medical research and the treatment of cancers
DDNews Cancer Research Exclusive: Turning an eye to TERT
By Kelsey Kaustinen, DDNews Senior Editor
As part of the TCGA initiative, researchers have discovered multiple cases of missing chromosomes in chromophobe renal cell carcinoma, as well as rearrangements in the promoter region of the TERT gene
Abbott and Merck go FISH
ABBOTT PARK, Ill.—Abbott will collaborate with Merck to evaluate the use of a fluorescence in-situ hybridization (FISH)-based companion diagnostic test to aid in the development of a Merck investigational cancer therapy.
FISH-based companion diagnostic tests are designed to identify specific DNA sequences to help guide physicians in determining which patients are more or less likely to benefit from a particular therapy. FISH technology has a variety of uses, an Abbott spokesperson points out. It can identify whether too many, or too few, copies of a particular gene are present or whether certain genes have rearrangements that play an active role in disease progression.
"The use of FISH to determine genomic status and the link to therapeutic outcome in oncology is one of the fastest-growing applications. In this instance, a FISH assay will be developed to examine copy number of the TP53 gene," she adds.
The Abbott FISH assay will be evaluated in clinical trials to help identify patients more likely to respond favorably to Merck's as-yet unidentified investigational cancer therapy.
Merck evaluated number of potential partners and Abbott was chosen as a partner to develop this companion diagnostic test.
"We have proven capabilities to take a product through the regulatory process, manufacturing, distribution and implementation in a clinical lab setting," the Abbott spokesperson says.
Merck will be responsible for establishing the clinical trial sites with regard to all aspects of patient recruitment and therapy administration. Abbott Molecular will work with Merck to select the FISH testing labs, and then Abbott will provide assay training and monitor the laboratory sites.
"Our goal through this collaboration, and others like it, is to ensure that the right medicine gets to the right patient," says Stafford O'Kelly, head of Abbott's molecular diagnostics business. "As one of the early pioneers in companion diagnostics, we believe that linking genetic testing with drug development at the earliest stages can increase the effectiveness and predictability of medicines and help physicians make more informed treatment decisions."
Abbott's portfolio of companion diagnostic tests includes the PathVysion HER-2 DNA Probe Kit, which represents one of the first examples of innovations in the field of personalized medicine. The test is approved for use in selecting breast cancer patients for whom Herceptin (trastuzumab) therapy is being considered. In addition, Abbott's Vysis ALK Break Apart FISH Probe kit was approved in 2011 for use in identifying non-small cell lung cancer patients for Pfizer's XALKORI (crizotinib) treatment in the United States, Canada, South Korea, Japan and a number of other markets. Global commercialization continues to progress as Xalkori and Vysis ALK receive additional individual country approvals, Abbott notes.
"Our collaboration with GSK was expanded in November 2011. The existing agreements focused on the development of PCR tests to screen non-small cell lung cancer and melanoma tumors for expression of the MAGE-A3 antigen. Under the expanded agreement, Abbott will develop a PCR test for use on the Abbott m2000rt instrument, to screen non-small cell lung cancer tumors for the expression of the PRAME antigen. PRAME is a preferentially expressed antigen of melanoma that is expressed in 69 percent of non-small cell lung cancer cases, as well as in a wide variety of cancer types, including melanoma, breast, ovarian and bladder cancer, with limited expression in normal cells," the spokesperson tells ddn.
Abbott Molecular is a leader in molecular diagnostics—the analysis of DNA and RNA at the molecular level. Abbott Molecular's tests can also detect subtle but key changes in patients' genes and chromosomes and have the potential for earlier detection or diagnosis, provide information relevant to the selection of appropriate therapies, and may improve monitoring of disease progression.
In an unrelated development, Abbott will collaborate with Genetics Laboratory Inc. (GenLab) on the development of a molecular diagnostic test that will be designed to rapidly detect microorganisms that cause orthopedic infections. Under terms of the agreement, Abbott, in conjunction with GenLab, will develop and commercialize the new assay for use on the PLEX-ID automated microbial identification system. In the United States, PLEX-ID is currently intended only for non-diagnostic use, but assays are now being developed for future clinical diagnostic uses.
PLEX-ID has the ability to rapidly identify a broad variety of microorganisms. The system is capable of generating results within five to six hours in contrast to other methods, which may take several days or longer for positive identification.
"Bacteria, particularly antibiotic-resistant species such as MRSA, are very dangerous in orthopedic patients because the bacterial colonies attach to the artificial surfaces of the implants," says Dr. Gerhard Maale, an orthopedic oncologic surgeon and an expert in orthopedic infections in the Dallas-Ft. Worth area.
Maale will also serve as the medical director for the Abbott-GenLab collaboration.
"A molecular diagnostic test designed to detect microorganisms that cause orthopedic infections, running on the PLEX-ID, could have the ability to determine which pathogens are responsible for an infection while assessing the genetic composition and potentially antibiotic resistance," Maale says. "This could be a major step forward in diagnosing and treating serious infections in artificial joint recipients, with the potential to provide important information to physicians that they could use to save treatment costs and improve the quality of life for these patients."
According to the New England Journal of Medicine, about 800,000 knee and hip replacement procedures are performed annually in the United States, and complications related to infections occur in approximately 2 percent of those procedures. In addition, more than 70,000 joint revisions are performed annually in the United States, with greater than 15 percent of hip and 25 percent of knee revisions caused by infections. Revisions are often more expensive than the original procedure.
FISH: Navigating the waters of personalized medicine
PRETREATMENT: Cells or tissue are placed on a slide and treated (fixed) to stabilize cellular structures. Chemical and enzymatic procedures are employed to remove membranes, and cytoplasmic proteins that prevent access to the cells' DNA.
DENATURATION: Cell DNA is exposed to high temperature in order to open the DNA, making it accessible to fluorescent-labeled probe DNA.
HYBRIDIZATION: Probe is added to the sample and allowed to combine with complementary sequence of the target DNA.
WASHING: Excess probe is removed post-hybridization, and a counterstain is applied to visualize the individual cells and nuclei.
FISH can utilize more than one fluorescent label at one time to be able to detect multiple genes (or gene loci) in a single hybridization. Colors are counted or enumerated to determine the gene status, amplification, deletion and translocation.