Two drugs used for breast and lung cancer can be combined to overcome tumor resistance in different types of the disease, new research suggests.
A study found that palbociclib medication for breast cancer was given a boost when combined with the treatment of crizotinib with lung cancer.
When tested on both laboratory cancer cells and mice with a range of malignant tumors, the duo was significantly more effective than the individual drugs.
The combined treatment blocked both cell division and induced senescence, which occurs when a cell loses its "power" to divide and grow.
Although palbociclib has been described in the past two decades as one of the largest treatment advances for advanced breast cancer, some tumors develop resistance to it.
This is often driven by a protein that targets crizotinib, where the two drugs together help to overcome resistance to cancer cells.
Two drugs used for breast and lung cancer could be combined to overcome tumor resistance in many forms of the disease, research suggests (stock)
The research was conducted by the Institute of Cancer Research (ICR) in London and the University Institute of London (UCL) Cancer Institute.
It was co-led by professor Paul Workman, chief executive of the ICR and Dr. Sibylle Mittnacht, professor of molecular cancer biology at the UCL.
Professor Mittnacht said: & # 39; Our evidence shows that existing drugs could be used to resist treatment in a frequent form of breast cancer in women.
& # 39; In addition, using a current breast cancer drug with these other drugs may be a new, promising route to treat lung cancer and various other forms of cancer. & # 39;
Professor Workman added: & # 39; The ability of cancer to adapt, evolve and become resistant to drugs is the biggest challenge we face in creating more effective treatments for the disease.
& # 39; We have demonstrated the potential to merge two breast and lung cancer precision drugs to create a two-pronged attack that relieves cancer cells of their resistance. & # 39;
Breast cancer affects one in eight women at some point in their lives in the UK and the US, statistics show.
When it comes to lung cancer, 47,735 cases were diagnosed in the UK between 2014 and 2016, according to Cancer Research UK statistics.
And in the US, about 234,000 people were told they had lung cancer last year, according to the American Lung Association.
Palbociclib is used to treat hormone receptor-positive breast cancer. These tumors are established as a direct result of the many hormone receptors on the surface of breast cells.
In the case of estrogen receptor-positive breast cancer, the cancer cells receive growth signals from the hormone.
WHAT ARE THE SYMPTOMS OF BREAST CANCER?
Approximately 55,200 people are diagnosed with breast cancer every year in the UK. One in eight women develops the disease during their lifetime.
The disease can cause a number of symptoms, but the first visible symptom is usually a lump or an area with thickened breast tissue.
Most breast nodules are not cancer, but it is always best to have them checked by your doctor.
According to NHS Choices, you should also see your doctor if you notice one of the following:
- A change in the size or shape of one or both breasts
- Release one of your nipples, possibly with blood streaks
- A lump or swelling in one of your armpits
- Nipping on the skin of your breasts
- A rash on or around your nipple
- A change in the appearance of your nipple, such as sunken in your breast
Breast pain is usually not a symptom of breast cancer.
Palbociclib blocks two proteins, called CDK4 and CDK6, that promote tumor cell division and cancer progression.
Tumors can become resistant to palbociclib by activating a molecule called CDK2, which stimulates cell division even when CDK4 and 6 are inactive.
CDK2 is supposed to do this via a signaling route that includes the molecules MET and FAK.
Crizotinib has been shown to block MET.
The researchers therefore speculated whether combining the two drugs could overcome the tumor-fueling mechanism of CDK2.
The treatment combination was tested in both cancer cells cultured in the laboratory and human tumors transplanted into mice.
These cancers include everything from breast and lungs to intestine.
Results – published in the journal Oncogene – revealed that duo therapy worked together to prevent the cancer cells from splitting and inducing senescence.
The effectiveness of the combined treatment for different types of cancer suggests that palbociclib has potential that goes beyond the pectoral forms of the disease.
In a second part of the experiment the researchers tried to discover how resistance to palbociclib arises.
Robotics and advanced imaging were used to identify how CDK2 is activated, so that rapidly dividing cells can avoid CDK4 and 6 inhibitors.
The researchers discovered that MET and FAK are critical molecules in the signaling pathway that tumors use to survive and to develop palbociclib resistance.
Before the combined treatment can be applied to patients, the safety and effectiveness of combining CDK4 and 6 inhibitors such as palbociclib with MET inhibitors such as crizotinib must be investigated, the researchers said.
If these studies are successful, it may be possible to develop laboratory tests that identify which patients would benefit from using crizotinib in this way.
And if we look further into the future, CDK4 and 6 inhibitors can be combined with drugs that block FAK.
FAK was found to be critical in the activation of unwanted CDK2. Inhibitors against this molecule are already being tested in clinical studies.
& # 39; We need to do even more to understand the full potential of a combination treatment to increase the effectiveness of these drugs & # 39 ;, says Professor Workman.
& # 39; But the approach looks promising and has the potential to be effective against different types of cancer. & # 39;
Combining different drugs with different mechanisms of action is a central strategy of the ICR research program to combat cancer's ability to adapt, develop and become resistant to cancer.
The ICR raises the last £ 15 million ($ 18.6 million) from an investment of £ 75 million ($ 93.2 million) for a new Center for Cancer Drug Discovery for a world first of & # 39; anti-evolution & # 39 therapies.
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