Palbociclib Combined With Paclitaxel Shows Effective For The Treatment Of ER Positive Breast Cancer

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Palbociclib Combined With Paclitaxel Shows Effective For The Treatment Of ER Positive Breast Cancer Breast cancer is a malignant tumor that occurs in the epithelial tissue of the breast glands. Global breast cancer incidence has been rising since the late 1970s. One in eight women in the United States will develop breast cancer in their lifetime. China is not a country with a high incidence of breast cancer, but it should not be optimistic. In recent years, the growth rate of the incidence of breast cancer in China has been 1 to 2 percentage points higher than that of high-risk countries. Breast cancer has become a common tumor that threatens women's physical and mental health.

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According to the study from the Perelman School of Medicine at the University of Pennsylvania, combining the new breast cancer drug palbociclib with paclitaxel (Taxol) can shrink the tumors in nearly half of patients with estrogen receptor (ER) positive breast cancer. This discovery provides new clues to how breast cancer develops resistance to palbociclib, which is a common phenomenon among many patients taking the drug. Compared with paclitaxel alone, this combination may be beneficial to patients. Based on this result, it is necessary to conduct a larger clinical trial to determine the benefit. "

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Electron micrograph of a single breast cancer cell.

A Complementary Therapy Palbociclib targets the rapid division of tumor cells by inhibiting the activity of CDK4 and CDK6 enzymes, which help drive cell division and are upregulated in most cancers. Researchers suspect that palbociclib's unique mechanism of action may make it a good companion to other breast cancer drugs (such as paclitaxel), which kills dividing cells at some point during cell division (also known as the "cell cycle"). Palbociclib can effectively halt the cell cycle before that point, so in principle it can synchronize cancer cells, making them more vulnerable to a closely following dose of paclitaxel.

To begin to validate the concept clinically, DeMichele and his colleagues treated 27 breast cancer patients with alternating doses of Palbociclib - administered daily for several days at a time - and paclitaxel administered once per week. .

The researchers finally determined the optimal dose of palbociclib at 75 mg per day, combined with a standard dose of paclitaxel.

The main purpose of the study was to determine whether this alternate dosing of the two drugs is safe enough for large-scale trials. The results show that this appeared to be the case. DeMichele said, although most participants developed the low-white-blood-cell count disease called neutropenia, which is a common side effect of palbociclib and other chemo drugs, it is generally not dangerous.

Due to this situation, some participants' palbociclib dose was reduced.

The team now hopes to set up such a trial. They also plan a similar trial using a newly developed CDK4/6 inhibitor, Novartis's ribociclib.

Although the trial was not designed to test whether the combination is more effective than paclitaxel for breast cancer, the patient's response is promising.

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Nearly half showed detectable tumors shrinking or disappearing for a long time.

DeMichele said: "This seems to be better than our expectation of paclitaxel alone, but the only way to determine the difference between the two is a randomized clinical trial of combination versus the single drug."

The team now hopes to conduct such an experiment. They also plan to conduct a similar test using the newly developed CDK4 / 6 inhibitor, Novartis' ribociclib.

Clues to Resistance In related research, DeMichele and her colleagues collaborated with the team of palbociclib manufacturer Pfizer to find molecular clues about how breast cancer develops resistance to the drug. By examining samples obtained from patients undergoing palbociclib treatment, the team found that as the tumor becomes resistant, these cells more than doubled their expression of several cell-cycle-driving genes, including PLK1, TOP2A, CDK1, and BUB1. Lab dish studies of tumor cells that develop resistance to palbociclib revealed similar changes.

Notably, the resistant cancer cells did not seem to lost the activity of the tumor suppressor RB1--a potential mechanism of drug resistance, because the CDK4 and CDK6 enzymes partly drive cell division by inhibiting RB1. The analysis also ruled out several other suspected mechanisms including changes in the CDK4/6 genes and estrogen receptor genes.

"Although the drug blocks two important cell cycle drivers, CDK4 and CDK6, other cell cycle genes can compensate for the increased expression levels, which allows tumor cells to start dividing again." DeMichele said. "It shows that we might be able to adding a drug that blocks other cell cycle drivers to prevent this resistance. " Huateng Pharma is committed to providing cost-effective pharmaceutical products and services to customers worldwide with the belief of “Strive for the Human Health". We can provide anti-cancer intermediate products, such as Palbociclib and Ribociclib which used for the treatment of certain kinds of breast cancer. We can make scale-up production with capacities varying from gram to kilograms and multi tons.

Palbociclib Intermediates: CAS NO. 571189-16-7, CAS No. 571188-59-5 Ribociclib Intermediates: CAS No.: 733039-20-8, CAS No. 571188-59-5, CAS No. 52092-47-4

Source: University of Pennsylvania School of Medicine