Lung cancer patients may live three months longer after scientists discovered a new combination of drugs that targets the condition’s “Death Star” protein.
The Death Star protein can be found in mutated forms of the KRAS gene, one of the most commonly mutated genes in cancer. It gets its nickname for its impenetrable, drug-resistant surface.
Previous drug trials attempted to target multiple KRAS mutations, but were unsuccessful due to severe side effects.
However, new research presented at the annual meeting of the American Society of Clinical Oncology has identified a compound that targets the protein, controls tumor growth, and limits toxicity for patients.
Thousands of patients could benefit
The research, led by a team from the Cancer Research Institute, London, and the Royal Marsden NHS Foundation Trust, could lead to a “new therapy paradigm” to target the Death Starexperts said.
Maybe thousands of patients could benefit of the treatment, as approximately 40 percent of lung cancers, 45 percent of bowel cancers, and 90 percent of pancreatic cancers are driven by KRAS mutations.
Phase one of the institute’s trial tested the drugs VS-6766 and everolimus in 30 patients with a range of KRAS mutations, including those with advanced lung, ovarian, and thyroid cancer.
In a previous trial VS-6766, in combination with another drug, defactinib, shrunk tumors in half of patients with ovarian cancer.
The latest research has targeted patients who have already tried several therapies, including chemotherapy and immunotherapy, but found that their cancers have developed against drug resistance.
Eleven patients in the trial had highly advanced, non-small cell lung cancer. Following the combination of drugs, half did not see their cancer progress in six months – twice the time expected after chemotherapy alone.
Two of the 11 patients with lung cancer saw their tumors shrink by more than 30 percent after the combination.
It has also produced responses in patients with advanced ovarian and thyroid cancers, which the researchers said they plan to study further.
To reduce side effects for patients, the trial used an innovative dosing schedule, where participants received the two drugs twice a week for three weeks, followed by a week off.
An “innovative” combination of drugs
The drug combination does not target the KRAS gene itself, but makes it less effective by blocking the two pathways it uses to drive tumor growth. Targeting it in two ways was aimed at delaying the development of drug resistance and preventing the progression of cancer, the experts said.
The first effective drug to treat one KRAS mutation, G12C, was launched in the NHS last year. But this new discovery could mean that the combination of drugs can be used to target cancers that are driven by multiple KRAS mutations.
Professor Udai Banerji, Deputy Director of Drug Development at the Cancer Research Institute, London, and the Royal Marsden NHS Foundation Trust, said: “Our early phase study shows that an innovative drug combination can effectively target several mutated versions of KRAS which is one of the most dangerous mutations in cancer, and one of the most difficult treatments to create against cancer.
“This could represent a new therapy paradigm to target KRAS mutations across multiple tumor types, including lung and low-grade serous ovarian cancer.”
The researchers now hope to confirm the findings in a larger patient cohort.
“Treatment changed lives”
Sally Wells, 53, from Dartford, was diagnosed with stage four ovarian cancer in 2016 and joined the test in 2019 at the Royal Marsden.
Three years later, the treatment proved effective and she was able to continue her normal life.
“I had six courses of chemotherapy, I lost my hair and, with that, I felt like I had lost myself too,” she said.
“Just before Christmas 2018, after running out of medical options, I was told that nothing else could be done for me and I returned home knowing that I was coming to the end of my life.
“Then I received the wonderful news that I was able to join this process at the Royal Marsden. It was my only hope, and I would do anything to prolong my life. It’s been three years and I’m fine.
“This treatment changed my life and allowed me to continue living a busy life with my children and grandchildren.”