Researchers at Weill Cornell Medical College and Memorial Sloan Kettering Cancer Center have discovered a previously undetected form of hormone-treated prostate cancer and a group of hormones that drive its growth. molecular. This discovery opens the door to the development of therapeutics to treat this specific disease.
Researchers at Weill Cornell Medical College and Memorial Sloan Kettering Cancer Center have discovered a previously undiscovered of hormone-treated prostate cancer, and a set of molecules that drive its growth. This discovery opens the door to the development of therapeutics to treat this specific disease.
In the study, published May 27 in the journal Science, researchers examined a method known as “castration” Molecular changes in advanced malignancies that resist “prostate cancer”, which occurs when tumors evade treatments that deprive them of the hormones they need to grow. Using samples from patients, they conducted a comprehensive investigation of the cancer.
“Our data show that there are four castration-resistant diseases, two of which have not been previously defined,” said co-author Dr. Ekta Khurana said he is an associate professor of physiology and biophysics at Weill Cornell Medical College.
She and her collaborators estimate that one type of tumor, which they call stem cell-like (SCL), accounts for about 50% of castration-resistant prostate cancer. quarter. In SCL tumor cells, they identified a group of proteins that together promote this intractable disease. Studies have shown that this same molecular pathway drives other solid tumors, including colorectal cancer and malignancies of the breast and lung, so scientists are already investigating ways to interfere with their activity.
Dr. Khurana said: “For patients who belong to the SCL group, we have identified very promising drug targets that future research will focus on. Validation.” Dr. Khurana is also co-leader of the Genetics and Epigenetics Program at the Sandra and Edward Meyer Cancer Center and a member of Weill Cornell Medicine’s Institute for Precision Medicine, England. Dr. Khurana conducted the study in collaboration with senior co-author Dr. Chen Yu at Memorial Sloan Kettering Cancer Center.
An estimated 268,000 men will develop prostate cancer this year. Researchers have known that this type of cancer includes more than one disease. Some tumors may manage to resist treatment but still need testosterone and other hormones collectively called androgens to grow. Meanwhile, others shed their androgen dependence and assumed an aggressive form called neuroendocrine. The new study identifies two other types of the disease: SCL and WNT, named signaling pathways that are overactive in these types of tumors.
Scientists seeking to study castration-resistant prostate cancer often lack enough cells from patients to capture its full diversity. For this study, however, the team obtained 40 tumor samples. Much of this came from the collection of organoids, tiny organoid structures grown from tumor cells collected from patients at Weill Cornell Medical College and Memorial Sloan Kettering Cancer Center.
The researchers analyzed the cells’ DNA, RNA, and how tightly their DNA was packaged, a feature known as chromatin reproducibility. and sex. Changes in this packaging lead to cancer by altering the availability of gene expression. The chromatin data allowed them to identify four groups, including SCL and WNT.
To determine the proportion of cases they each likely constituted, the researchers used RNA-sequencing data from Weill Cornell Medicine. of 100 patients and 266 patients from the “Stand Up To Cancer” organization were classified. Depending on the patient type, 22% to 30% of patients were classified as SCL, while WNT accounted for 5% or 7%.
Focusing on SCL, they use sophisticated computational tools to integrate molecular data and identify faulty pathways at the heart of cancer. These proteins, FOSL1, TEAD, YAP and TAZ, become overactive and alter chromatin accessibility, thereby driving tumor growth. In experiments, the researchers found that two molecules known to interfere with these proteins slowed the growth of SCL cells, but not androgen-dependent cells — a result that underscores the potential for targeted therapy.
“Once you can identify the patient’s tumor type, that’s very powerful information,” Dr. Khurana said.
References
Chromatin profiles classify castration-resistant prostate cancers suggesting therapeutic targets