UC San Francisco scientists have calculated why some lung cancer has responded to initial drug treatment resistance. In the process, they have designed a new approach to the treatment of these cancers in the laboratory, and they make promising medicine a promising future for the future. The research is published in a research published on the 26th of this month Natural Medicine.
Cancer Outsmarts Precision Therapy
Some lung cancer are mutations in a protein called EGFR. Usually the EGFR complex molecular circuit '' on / off '' This mode works when the cell counts when it grows and splits (and not when it is). In the circuit, in general, when it is extinguished, the mutant forms of EGFR in lung cancer & # 39; on & # 39; They are stuck in position. This leads to abnormal proliferation of cells and makes tissue healthy in tissues.
Even though scientists develop designer mutagenic EGFR mutants and activate tumor self-destructive machines, they are rarely susceptible to medication. However, the three-generation generation of more and more powerful precision instruments that target particular mutant proteins results are always the same: 18 months later and later. And when the tumor is returned, drugs are more durable and more aggressive than ever.
"Accuracy is a medicine command that allows patients to treat patients with special forms of cancer, but for all hypersensitivity, precision medicine often has no potential. Unfortunate clinical reality is resolved," said Dr. Sourav Bandyopadhyay, UCSF's bioengineering and science Author of the new therapist teacher and researcher.
Bandyopadhyay says there is a reason that there is a vacuum that separates the promise of precision therapy and that its real efficacy is the clever tumors. They are capable of redirecting the internal circuits and inventing new strategies for survival, although initially due to the shock of therapy. Researchers have also shown that although drug resistance continues to be resistant to drugs, the recovery of the EGFR activity continues, the tumor will no longer rely on protein mutants. Bandyopadhyay wanted to know why.
Aurora Cancer 's Achilles' Heel & # 39; it is created as
In order to identify drivers with Drug resistance, the researchers took multiple lines of cellular cancer with mutated EGFR and treated with cultural dishes with osimertinib or rociletinib, a mutant protein, with third-generation drugs. Osimertinib is approved for the treatment of EGF cells for non-small cell lung cancer. After the administration of drugs that appeared to have died of cancer cells, six weeks later they recovered both.
After stopping EGFR drugs after cancer cells, the researchers tested 94 more medicines, if they had resistance to them. Aurora Kinase A, a protein called osimertinib or rocetinetin, was killed by cancer cells once and for all.
Patients with joint cancer who transplanted tumor-resistant tumors were seen mice similar to direct results. Although tumors continued to continue, mice only treated with EGFR drugs, at the same time two proteins were predicted, with two tumults reducing their toxicity with the mouse.
"Aurora kinase has never been linked to drug resistance to cancer. It's basically a new path to endurance," said Bandyopadhyay, UCSF Helen Diller Family Comprehensive Health Center.
Aurora helps Cancer Escape Death
Researchers have demonstrated that Aurora tumors have not grown. Therefore, the Aurora-only treatment system is not advanced by cancer. What Aurora gives death is a way of escape from illnesses.
Osimertinib and rociletinib turn off the EGFR mutant. When cancer growth does not slow down, it triggers self-destructive circuits because it breaks and kills tumors. This is to recover the tumors and activate the aurora.
Aurora is a cancer escapist. Regardless of EGFR's independence, Aurora silences the cell suicide circuits, which means that EGFR circuits are circulating, ensuring continued survival of cancer. The Aurora and EGFR mutants were transported to a tandem, sealing the fate of the sealant to seal the fate of the seal to seal their solitary refuge.
Clinically significant finding
Unlike researchers, they found a new way of resisting drug-resistant tumors, as well as identifying biologists, whether the doctors were treating lung cancer, combined therapy such as EGFR and Aurora.
Researchers have found high levels of a protein called TPX2 at an advanced stage, many patients taking drug-resistance in lung cancer. They believe that TPX2 is known to activate the Aurora kinase to identify the patient's tumor that matches the therapies.
The next step, says Bandyopadhyay, is to get its two point vision and the TPX2 biomarker is approved for clinical trials.
"While more and more patients are moving forward with third-generation EGFR inhibitors, our work describes a new mechanism of resistance in most patients and is used by existing Aurora kinase inhibitors. We hope this work confirms interest in Pharma cell cycle inhibitors , such as auroraine kinase inhibitors, believe that the molecule class is an incredible force that is combined with other therapies, that is, they have not historically been tested. We hope our results have been catalyzed by the start of new trials, so that EGFR mutants can combine our combined approach with " .