What Do You Know About CDK4/6 Inhibitors For Breast Cancer?

Many people are afraid of talking about “cancer”. Cancer is a disease in which healthy cells in the body change and become uncontrolled cells that only know how to differentiate and grow without performing their own functions, and may even spread to other parts of the body.

According to the latest global cancer burden data for 2020 released by the International Agency for Research on Cancer (IARC) of the World Health Organization, breast cancer has surpassed lung cancer as the number one cancer in the world. And how much do we know about the incidence of breast cancer and the latest treatment options?

Is breast cancer only for women?

Many people think that breast cancer is the patent of women, and it is true that most of the breast cancer patients are women, mainly because of the malignant tumor cells in the breast cells. In fact, men are more likely to develop breast cancer because breast cancer is an estrogen-dependent tumor.

Older men also have an increased chance of developing breast cancer as their body’s production of androgens decreases, especially in those who are obese and have unreasonable diets and lifestyles.

DK4/6 inhibitors: an option for HR+/HER2- advanced breast cancer patients

Breast cancer is one of the more effectively treated cancers today, with a 5-year survival rate that can be as high as 90%. Surgery, chemotherapy, radiation therapy, targeted therapy, and endocrine therapy are usually used. Doctors will choose a combination of treatments that are not generic depending on the patient’s condition. Sixty percent of breast cancer patients are in the hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer category. Among them, CDK4/6 inhibitors are the most successful new class of drugs in the field of first- and second-line treatment for HR+/HER2- advanced breast cancer in recent years.

The first positive CDK4/6 inhibitor for early-stage breast cancer has been approved by FDA in October 2021 and approved by NMPA in early January this year, CDK4/6 inhibitor adjuvant therapy for early-stage breast cancer has officially taken the first step.

1. CDK4/6 inhibitors inhibit cancer mechanism

The proliferation of our normal cells is under strict regulatory mechanism, while tumor cells are the result of deregulation of cell proliferation, which leads to uncontrolled proliferation “evil”. Scientists have found that CDK4/6 is over-expressed in many cancers, including breast cancer, and is a hallmark feature of cancer. The possible mechanism for this is that the first activation of cyclin-dependent kinases (CDKs) in response to mitogenic stimulation is cytokinin-dependent kinase 4 (CDK4) and cytokinin-dependent kinase 6 (CDK6), which bind to cyclin D (cytokinin D) and promote hyperphosphorylation and inactivation of the retinoblastoma protein (Rb), followed by the release of the transcription factor E2F, which drives the cell cycle through the S phase, and subsequently the S phase. This drives the cell cycle through S-phase, resulting in uncontrolled cell division cycle. Therefore, CDK4/6 inhibitors can selectively inhibit CDK4/6 to restore the normal regulation of the cell cycle and can target and block DNA synthesis and proliferation of tumor cells.

2. Research progress of CDK4/6 inhibitors for breast cancer

The results of PALOMA-2 study showed that the median progression-free survival time of piperacillin combined with endocrine therapy in first-line treatment was 27.6 months, which was significantly better than that of endocrine monotherapy at 14.5 months. Also, piperacillin combined with endocrine therapy significantly prolonged the progression-free survival time for both patients with bone metastases and those with visceral metastases. Real-world studies such as P-REALITY and IRIS in the US, showed the overall survival benefit of piperacillin in the treatment of HR+/HER2- advanced breast cancer. Therefore, CDK4/6 inhibitors such as piperacillin have become the first-line option of choice for HR+/HER2-advanced breast cancer in important guidelines in China and abroad.

Conclusion

CDK4/6 inhibitors have broken through the bottleneck of traditional treatment for HR+/HER2-advanced breast cancer and are leading the breakthrough and innovation in the clinical treatment paradigm of breast cancer, but more clinical studies are needed to further validate the efficacy and safety of CDK4/6 inhibitors in combination with endocrine adjuvant therapy.