Most breast tumors contain estrogen receptors on the cell surface - a cancer called ER-positive.
Studies show that approximately 70% of all breast cancers are ER-positive.
The chemical signals transmitted by the hormone estrogen contribute to tumor growth. To stop ER-positive cancer, doctors prescribe special drugs - anti-estrogens.
Such drugs as tamoxifen and fulvestrant prevent the spread of the tumor by suppressing the estrogen receptors or hormone production in the body. This is called endocrine therapy.
But in about a third of cases, the cancer becomes resistant to treatment - resistance develops, which badly affects the chances of patients.
Why is this happening?.
The mechanisms underlying the resistance of tumors to therapy are not entirely understood, and presently present a serious scientific problem.
A new discovery in the genetics of cancer.
In recent months, experts from the Dana-Farber Cancer Institute in Boston (USA) have made significant progress in understanding the resistance of cancer to endocrine therapy.
Dr. Myles Brown, director of the Center for Functional Epigenetics of Cancer at the Institute, spoke about specific mutations that make cancer cells more resistant and contribute to metastasis. The discovery of American researchers can lead to the emergence of more effective drugs for patients who are no longer helped by traditional methods of treatment.
The results of the study are published in the journal Cancer Cell.
Neomorphic mutations interfere with cancer treatment.
Earlier, Dr. Rinath Jeselsohn (also involved in the latter project) was able to find out that mutations in the estrogen receptor gene are largely responsible for the resistance of tumor cells to treatment.
After this discovery, Dr. Jezelson and her colleagues analyzed new mutations using laboratory models of ER-positive breast cancer, noting that they maintain tumor resistance to tamoxifen and fulvestrant.
Now, additional mechanisms have been discovered that will help doctors to fight cancer more effectively. Not only does mutant genes adapt cells to low concentrations of estrogens, they also stimulate the appearance of metastases.
Similar mutations that allow genes to acquire amazing new functions are called neomorphic mutations.
"We found that the effect of genetic mutations is twofold, allowing the tumor to act simultaneously along two" front lines ". Endocrine therapy produces a natural selection of cells that can grow in conditions of a lack of estrogen, but also increases the metastatic potential, "notes Dr. Brown.
Combined therapy of resistant breast cancer.
Noting the impact of mutations on the survivability of cancer, scientists turned to modern tools for editing the genome - CRISPR-Cas9. Genetic analysis has shown that CDK7 (a gene of cyclin-dependent kinase 7 type) can serve as a more reliable target for the treatment of cancer.
Moreover, a suitable medicine already exists:
a few years ago a certain scientist Nathaniel Gray (Nathanael Gray) proposed an experimental inhibitor of CDK7-THZ1.
The combination of fulvestrant and THZ1 proved effective both in cell cultures of ER-positive breast cancer and in animal models. Two drugs significantly slowed the growth of the tumor, and resistance was practically not observed.
Dr. Brown and his colleagues believe that such combination therapy of breast cancer will completely solve the issue of resistance. The first clinical trials can begin as early as next year.
medbe. en.