Palbociclib Combined With Paclitaxel Shows Effective For The Treatment Of ER Positive Breast Cancer .pdf
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Palbociclib Combined With
Paclitaxel Shows Effective For
The Treatment Of ER Positive
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.
Image from MedicalXpress
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. "
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.
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
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
Source: University of Pennsylvania School of Medicine