Protein Discovery May Explain Why Patients Develop Resistance to New Anti-cancer Drugs
A team of researchers at the University of Cambridge has identified a protein complex that might explain why some cancer patients treated with the revolutionary new anti-cancer drugs, known as PARP inhibitors, develop resistance to their medication.
In a study published in Nature Cell Biology, the team from the Wellcome/Cancer Research UK Gurdon Institute show that Shieldin, termed because it shields the ends of broken DNA, regulates DNA repair and could be a useful marker for identifying what patients are likely to respond poorly to PARP inhibitors.
The DNA in our cells is susceptible to damage caused by external factors such as sunlight or smoking, or internal factors including our genetics. One form of damage is when both strands of the DNA double helix break. This can lead to cell death, so cells have various repair mechanisms to fix the damage.
The simplest mechanism for repairing DNA breaks is known as non-homologous end-joining (NHEJ). This mechanism essentially sticks together the broken DNA strands, but it is imperfect and can result in deletions of segments of DNA.
A more accurate repair mechanism is homologous recombination (HR). This mechanism uses a copy of our DNA as a reference text to fill in any missing gaps.
However, NHEJ and HR work in competition against each other: if the balance is tipped in favor of HR, then cells will use this mechanism to repair the DNA damage.