Cancer uses devious means to evade treatment and survive. One prime example is the way tumors express anti-cell death (anti-apoptotic) proteins to resist chemotherapy and radiation. However, the Pellecchia laboratory at Sanford-Burnham Medical Research Institute (Sanford-Burnham) has made two recent discoveries that may help curb these anti-apoptotic proteins and make current treatments more effective.
In a paper published online in the journal Cell Death and Disease on May 6, Maurizio Pellecchia, Ph.D., and colleagues outline how the six anti-apoptotic proteins in the Bcl-2 family are expressed differently in different cancers. As a result, any therapy designed to defeat these proteins, and thus enhance the cell death caused by most cancer treatments, must target the exact anti-apoptotic protein the cancer is expressing to be effective. However, even targeting the right protein might not be enough, as cancers often express more than one and can select for an "escape" protein and continue to thrive.
"You need to inhibit all six of the anti-apoptotic proteins members of the Bcl-2 family to have a compound with therapeutic potential," says Dr. Pellecchia.
Related research may have solved that problem. The Pellecchia laboratory, in collaboration with Coronado Biosciences and Virginia Commonwealth University, has been working on just such a pan-Bcl-2 inhibitor, and may have found it in a compound called BI-97C1. A paper published online on May 5 in the Journal of Medicinal Chemistry describes how BI-97C1, an optically pure derivative of a cottonseed extract called gossypol, inhibits all six anti-apoptotic Bcl -2 family proteins. This broad spectrum approach could make current cancer treatments more effective by controlling all six of these proteins and allowing malignant cells to die.
"When we tested BI-97C1 against human prostate cancer in mice, the cancer was completely wiped out, even with one tenth the dose we had used with previous compounds," says Dr. Pellecchia.
BI-97C1 is currently licensed to Coronado Biosciences, a private, clinical stage biotech company focused on new cancer treatments. Coronado's pan Bcl-2 inhibitor program is expected to enter clinical trials soon. "We have a very productive collaboration with Dr. Pellecchia," says R.J. Tesi, M.D., president and CEO of Coronado Biosciences. "His work demonstrates the importance of inhibiting all six Bcl-2 pro-survival proteins and demonstrates how rational drug design can optimize the development of targeted therapies to treat cancer. We are anxious to move BI-97C1 from pre-clinical development into patients."
About Sanford-Burnham Medical Research Institute
Sanford-Burnham Medical Research Institute (formerly Burnham Institute for Medical Research) is dedicated to discovering the fundamental molecular causes of disease and devising the innovative therapies of tomorrow. Sanford-Burnham, with operations in California and Florida, is one of the fastest-growing research institutes in the country. The Institute ranks among the top independent research institutions nationally for NIH grant funding and among the top organizations worldwide for its research impact. From 1999 – 2009, Sanford-Burnham ranked #1 worldwide among all types of organizations in the fields of biology and biochemistry for the impact of its research publications, defined by citations per publication, according to the Institute for Scientific Information. According to government statistics, Sanford-Burnham ranks #2 nationally among all organizations in capital efficiency of generating patents, defined by the number of patents issued per grant dollars awarded.
Sanford-Burnham utilizes a unique, collaborative approach to medical research and has established major research programs in cancer, neurodegeneration, diabetes, and infectious, inflammatory, and childhood diseases. The Institute is especially known for its world-class capabilities in stem cell research and drug discovery technologies. Sanford-Burnham is a nonprofit public benefit corporation. For more information, please visit www.sanfordburnham.org.
Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute
Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy