The UCSF team's findings imply that new first-line combination therapies are necessary to treat the full array of mutations that can worsen a patient’s cancer and thwart drug resistance.
Trever Bivona, M.D., Ph.D., a UCSF Medical Center oncologist, said, "Currently we treat patients as if different oncogene mutations are mutually exclusive. If you have an EGFR mutation we treat you with one class of drugs, and if you have a KRAS mutation we pick a different class of drugs. Now we see such mutations regularly coexist, and so we need to adapt our approach to treatment."
Lung cancer is currently the leading cause of cancer-related deaths around the globe. Due to efforts to identify genetic mutations that drive the disease, targeted treatments were developed to help improve the life expectancy of many patients. However, these drugs are often only good for temporary remission because more often than not, cancers unavoidably develop drug resistance and return, deadlier than ever. (Related: How Cancer is Mainly Caused by The Intake of Acidic Food.)
The latest UCSF-led study, that studied tumor DNA from over 2,000 patients in collaboration with Guardant Health, was the pioneer when it came to broadly profiling the genetic landscape of advanced-stage non-small cell (NSC) lung cancer, which is the most common form of the disease.
Bivona added that because the field was too intent on addressing the "driver" mutation controlling a tumor’s growth, many believed that drug-resistance evolved from new mutations in that same oncogene. The study has proven that "there are many different genetic routes a tumor can take" as it develops resistance to treatment. Bivona, also posited that this could be one reason "why many tumors are already drug-resistant when treatment is first applied.”
Bivona’s team worked with Guardant Health to determine the genetic landscape of stage 4 lung cancer using the “liquid biopsy” data from 1,122 patients in Guardant Health’s database. These patients were noted to have tumors with a mutated EGFR gene, which is believed to be the dominant genetic driver of at least 15 percent of cases of NSC lung cancer, along with 944 patients whose tumors lacked this mutation.
The researchers identified the mutations that showed up specifically in patients who developed resistance to EGFR-targeted drugs, which implies that these mutations, and not alterations in EGFR itself, are the reason for the onset of resistance. Studying a smaller subset of patients whose tumor DNA was collected at multiple stages of treatment, and whose clinical treatment history was recorded, confirmed these findings. Tumors "become more genetically complex and accrue more additional mutations" after exposure to multiple rounds of targeted drugs.
Bivona explained that the analysis could mean that a drug targeted at the EGFR mutation can help wipe out the cells carrying that mutation alone. But they often leave behind, and possibly even enhance, cells with additional mutations. Bivona considers that all they've done is to simply "reshape the landscape of the tumor," which leads to temporary remission that only makes the problem harder to solve once cancer returns.
While these findings imply that drugs are the go-to cure for lung cancer, consider trying some tips to prevent it instead.
You can boost your immune system by:
Learn more natural ways to prevent cancer at Healing.news.