The scientific community has made significant strides in recent years in identifying important genetic contributors to malignancy and developing therapeutic agents that target altered genes and proteins.
A recent approach to treat cancer called synthetic lethality takes advantage of genetic alterations in cancer cells that make them more susceptible to certain drugs. Alan F. List, MD, president and CEO of Moffitt Cancer Center, co-authored an article on synthetic lethality featured in the October 30 issue of the New England Journal of Medicine.
“Genetic alterations in cancer in humans may involve gene inactivation, amplification or inactivation,” said List. These changes are not present in nonmalignant cells. Common chemotherapeutic agents aggressively kill tumor cells irrespective of genetic alterations. They also have a negative impact on normal cells and can cause significant side effects. Synthetic lethality harnesses the genetic differences between tumor cells and normal cells to minimize the effects on normal cells, and maximize a drug’s effects on cancer cells.
Synthetic lethality can target a variety of cellular defects, including alterations in DNA repair, cell-cycle control and metabolism. This approach can also be used to target interactions between tumor cells and surrounding normal cells that promote tumor survival and oncogenes that drive tumorigenesis that are difficult to target directly. Many of the synthetic lethal drugs and targets have been identified in large-scale drug screens of the entire human genome.
An example of synthetic lethality is the recent approach being investigated to treat breast cancer patients with BRCA1 and BRCA2 mutations. BRCA1 plays an important role is repairing damaged DNA. Women who have mutations in BRCA1 or BRCA2 have an increased risk of developing breast and ovarian cancer because their cells cannot properly repair DNA. This suggests that BRCA mutated breast cancer cells may be more susceptible to drugs that target DNA. Laboratory studies have confirmed this hypothesis by showing that agents that target another DNA repair protein called PARP significantly kill BRCA mutated cells. Several PARP inhibitors are now being investigated in clinical trials in breast cancer patients, and early results are promising.
“The goal of current anticancer approaches is to offer individualized and highly selective therapy. The treatment model for many anticancer approaches has been expanded, with movement away from dose-intensive, non-targeted cytotoxic agents to combination chemoimmunotherapy, new therapeutic combinations and targeted agents,” said List. Synthetic lethality approaches may provide an additional avenue for individualized patient treatment.
About Moffitt Cancer Center
Located in Tampa, Moffitt is one of only 41 National Cancer Institute-designated Comprehensive Cancer Centers, a distinction that recognizes Moffitt’s excellence in research, its contributions to clinical trials, prevention and cancer control. Moffitt is the top-ranked cancer hospital in the Southeast and has been listed in U.S. News & World Report’s “Best Hospitals” for cancer since 1999. With more than 4,500 employees, Moffitt has an economic impact on Florida of nearly $1.6 billion. For more information, visit MOFFITT.org, and follow the Moffitt momentum on Facebook, Twitter and YouTube.
Kim Polacek | EurekAlert!
One step closer to reality
20.04.2018 | Max-Planck-Institut für Entwicklungsbiologie
The dark side of cichlid fish: from cannibal to caregiver
20.04.2018 | Veterinärmedizinische Universität Wien
University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.
Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.
Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...
In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
20.04.2018 | Physics and Astronomy
20.04.2018 | Interdisciplinary Research
20.04.2018 | Physics and Astronomy