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A new study shows that bad cancer and lung cancer drugs could be used together to overcome treatment resistance in many types of tumors.
Scientists found that when palbociclib, an anticancer drug in the bad, was badociated with crizotinib, a lung cancer drug, the combination of two drugs was significantly more effective against cancer cells in the laboratory than one or the other. other drugs used alone.
Palbociclib has been described as one of the greatest advances in women with advanced bad cancer for 20 years. It is therefore exciting to be able to further improve the effectiveness of the treatment.
The new findings also suggest that the combined approach could expand the clinical use of palbociclib – and other drugs that work in the same way – beyond bad cancer to also include many other types of tumors.
Scientists from the Institute of Cancer Research of London and the UCL Cancer Institute have discovered that palbociclib resistance is often caused by a crizotinib-targeted protein, which justifies the joint use of these two drugs.
Their new study is published today (Friday) in the journal oncogenic and was funded by Wellcome.
Palbociclib is part of a group of drugs currently used to treat patients with hormone receptor-positive bad cancer by blocking the function of two proteins – CDK4 and CDK6 – that promote tumor cell division. and the progression of cancer.
However, cancers can become resistant to palbociclib by activating a cognate molecule called CDK2, capable of driving cell division in the absence of CDK4 / 6.
In this new study, researchers found that CDK2 could compensate for inhibition of CDK4 / 6 in cancer cells by signaling via a cellular control pathway involving key MET and FAK molecules.
Based on this discovery, the researchers discovered that the combination of a CDK4 / 6 inhibitor, such as palbociclib, with a crizotinib – which blocks the activity of the MOS – has created a combined treatment much more effective than a single drug against cancer cells grown in the laboratory or in humans. tumors developing in mice.
The combined agents synergized not only to block the division of cancer cells but also to induce senescence – a condition in which cells would stop growing and dividing, but without cell death.
The researchers have achieved promising results on cancer cells derived from different organs of the body – from bad to lung through the intestine – indicating that there is a potential for extension of the cancer. Clinical use of palbociclib and other CDK4 / 6 inhibitors beyond bad cancer to benefit a larger number of patients. .
To reveal the underlying mechanism of resistance, the researchers conducted a systematic search using robotics and sophisticated imaging to identify the mode of activation of CDK2 in order to allow cells to evade the inhibitors of CDK4 / 6.
They discovered that MET and FAK are essential molecules in the signaling pathway used by cancer cells to survive and develop resistance to palbociclib treatment.
The researchers hope that their findings can be pbaded on to patients – first by badessing the safety and efficacy of the combination of CDK4 / 6 inhibitors such as palbociclib with MET inhibitors, such as crizotinib.
It may be possible to develop laboratory tests to identify patients who might benefit from using crizotinib in this way.
And, a little further in the future, researchers also point to the possibility that their research suggests that the combination of CDK4 / 6 inhibitors with FAK blocking drugs may be even more effective and more generally applicable.
Indeed, their results show that FAK is a critical node in cellular circuits leading to an undesirable activation of CDK2.
FAK inhibitors are already undergoing clinical trials and this idea could therefore be tested soon.
The combination of targeted drugs with different mechanisms of action is one of the central strategies that the Institute for Cancer Research (ICR) is pursuing as part of an innovative research program aimed at combating cancer capacity to adapt, evolve and become resistant to drugs.
ICR – a charity and a research institute – raises last £ 15 million from £ 75 million investment in new cancer research center to house innovative program anti-evolution therapies.
The co-leader of the study, Professor Paul Workman, general manager of the London Cancer Institute, said:
"The ability of cancer to adapt, evolve and become drug-resistant is the main challenge we face in creating more effective treatments for the disease." In this study, we sought to understand exactly how showed resistance to an important family of bad cancer drugs, can stay one step ahead of cancer.
"We have demonstrated the possibility of combining two precision bad cancer and lung cancer drugs to create a two-pronged attack that rids cancer cells of their resistance, and we need to do more to understand the full potential of cancer. combination therapy to increase the effectiveness of these drugs, but the approach seems very promising and could be effective against several types of cancer. "
Professor Sibylle Mittnacht, Professor of Molecular Cancer Biology at the UCL Cancer Institute, co-head of the study, said:
"Our evidence shows that existing drugs could be used to overcome resistance to the treatment of a common form of bad cancer in women.
"In addition, the use of a current bad cancer drug with these other drugs could be a promising new avenue for the treatment of lung cancer and several other cancers."
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Notes to editors
For more information, please contact Tilly Haynes at the ICR Press Department at 020 7153 5136 or at [email protected]. For inquiries outside office hours, please call 07595 963 613.
The Institute of Cancer Research London is one of the world's most influential cancer research organizations.
Scientists and clinicians at the Institute of Cancer (ICR) work every day to make a real impact on the lives of cancer patients. Through its unique partnership with the Royal Marsden NHS Foundation Trust and its "bed-to-bed" approach, the ICR is able to create and deliver results in a way that other institutions can not. not. Together, the two organizations are in the top four cancer research and treatment centers around the world.
The ICR has an outstanding track record of achievements dating back more than 100 years. He provided the first compelling evidence that DNA damage is the root cause of cancer, thus laying the groundwork for the now universally recognized idea that cancer is a genetic disease. He is now a world leader in the identification of cancer-related genes and the discovery of new targeted drugs for the personalized treatment of cancer.
College of the University of London, the ICR is the premier academic institution in the UK for the quality of research. It provides internationally renowned postgraduate education. It has the status of charity and relies on the support of partner organizations, charities and the general public.
The mission of the ICR is to make the discoveries needed to defeat cancer.
For more information, visit http: // www.
About UCL
The UCL was founded in 1826. We were the first English university created after Oxford and Cambridge, the first to open higher education to those who were excluded, and the first to provide systematic instruction in law , architecture and medicine.
We are among the best universities in the world, as evidenced by the performance of many international rankings and charts, and we are committed to improving the world.
Our community of more than 41,500 students from 150 countries and more than 12,500 staff members pursues academic excellence, transcends borders and has a positive impact on real world problems.
http: // www.
About Wellcome
Wellcome exists to improve health by helping good ideas flourish.
We support researchers, we face great health challenges, we campaign for better science, and we help everyone to participate in scientific research and health.
We are an independent foundation politically and financially.
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