Cancer can be stopped in its tracks by a mutant gene, without any outside help from toxic chemotherapy drug say American researchers.
While studying the mechanisms of gene integrity, researchers from Case Western Reserve University unexpectedly discovered an active mutant form of human Checkpoint Kinase 1 (Chk1) – which is also a non-natural form of the gene.
The mutation changed the protein conformation of Chk1 from the inactive to the active form which, when expressed in cancer cells, permanently stopped cell proliferation and caused apoptosis without the addition of any chemotherapeutic drugs.
“We have identified a new direction for cancer therapy and the new direction is leading us to a reduction in toxicity in cancer therapy, compared with chemotherapy or radiation therapy,” said Dr Youwei Zhang. “With this discovery, scientists could stop the proliferation of cancer cells, allowing physicians time to fix cells and genetic errors.”
Cells react to DNA damage by activating networks of signalling pathways known as cell cycle checkpoints – central to which is Chk1. The protein kinase aids cell survival – including cancer cells – under stress by placing a temporary stop on cell cycle progression and coordinating repair programs to fix DNA errors.
Chk1 inhibitors, used in combination with chemotherapy or radiotherapy, have been suggested to enhance the therapies’ anti-cancer effects, but as yet no inhibitor has passed the clinical trial stage III. This new strategy has the potential to achieve the same cancer killing effect as a Chk1 inhibitor/chemotherapy combination, but without the toxic drug.
Zhang and his colleagues will now consider two possible approaches to artificially activating Chk1 in cancer cells. One uses gene therapy to deliver the active mutant form into cancer cells, while the other involves searching for small molecules capable of inducing the same conformational change of Chk1, which can travel to cancer cells to activate Chk1 molecules.