CDK inhibitors: why women - and men - need to know about this 'new era' of cancer treatment (2023)

From wearing pink to correctly identifying a ribbon, breast cancer has an ingrained cultural presence. Both the color pink and the cancer ribbon are also a reminder of how common the disease is: breast cancer remains the second most common cancer among women in the United States (second only to skin cancer) and the secondleading cause of cancer death among women in the United States(second only to lung cancer).

Despite this global recognition of breast cancer, understanding of treatment options for breast cancer – or any other type of cancer – is not always followed. PBS news schedulefoundthat those actually diagnosed with cancer were often confused by medical terms, unable to understand the severity of their case, or too overwhelmed to discuss various treatment options.

As a result, another way to support cancer patients — beyond wearing a breast cancer rouge or ribbon — is to increase general health knowledge, such as learning about the different types of cancer treatment options. In particular, one option could be to enter "new Agetreatment: cyclin-dependent kinase (CDK) inhibitors.

Today's treatments:

Cyclin-dependent kinases (CDKs) regulate a healthy cell cycle; activation of these enzymes helps with cell division. However, if a cell becomes cancerous, the work of the CDKs can cause the cancer to proliferate, allowing the cancer cells to continue dividing, multiplying andspread throughout the body.

(Video) Role of CDK Inhibitors in the Treatment of Advanced Breast Cancer

CDK inhibitors are a type of cancer treatment - a drug such as that given during chemotherapy - that blocks CDK activity, inhibits cell division and slows the growth and spread of cancer cells. As of 2015, the Food and Drug Administrationapproved three types of CDK inhibitors(abemaciclib, palbociclib and ribociclib) for CDK 4 and 6: two enzymes that represent "driving forcethe formation of cancerous tumors in several different types of cancer. Currently, these drugs are only used to treat a specific type of cancer:hormone receptor positive (HR+) ERBB2 negative(ERBB2-, formerly known as HER2-) metastatic breast cancer that isthe most common subtypebreast cancer in women.


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(Video) CDK 4/6 inhibitors for older women with HR-positive breast cancer
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Despite the relatively limited use of these CDK inhibitors, an articlegradesthat its development is "probably one of the most clinically important discoveries" for patients with HR+ ERBB2- breast cancer. Treating them with a combinationhormone therapy and CDK 4/6 inhibitorcan give them more timeabout 12 months) from the spread of cancer and higher overall survival rates than those treated with hormone therapy alone.

Resistance Encounter:

However, CDK inhibitors face a potential obstacle: the cell's ability to create resistance to the inhibitors.

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Cancer cells that have not been killed by previous lines of treatment can develop resistance to the same treatments, limiting their effectiveness in the future. This resistance is not unique to CDKs and CDK inhibitors: for example, a new influenza vaccine is available every year because the influenza virus may have developed resistance to the previous year's vaccine, reducing its usefulness.

For context, the World Health Organization estimates that290,000 to 650,000 peopledie each year from flu-related causes around the world. For cancer, that number is approx.10 million- and, as a 2019 article inNature summed up"Drug resistance remains a major limiting factor in curing cancer patients." Particularly with CDK, if CDK4 is inhibited - for example by cancer treatment - CDK2 will take over and multiply the cancer cells. These cells will not only continue to grow, but will also be resistant to prior treatment with CDK inhibitors.

A hypothetical way to mitigate the effect of CDK2 is to target it individually: with a CDK inhibitor dedicated to it. The reality is that CDK2 has a receptor "pocket" identical to CDK1, which is an essential protein. A drug that accidentally fills the CDK1 compartment instead of CDK2 can prevent intestinal cells from replicating and lead to gastrointestinal (GI) problems. It can also prevent blood cell replication and reduce the body's ability to fight disease. Because of this risk, there have only been limited (and unsuccessful) attempts to target CDK2 - and even those few tests have resulted inmultimillion lossesdue to the costs of carrying out an oncological clinical trial, even in its first phase (earlier and cheaper).

"Better Days and More Days"

Another solution is CDK2 target not alone butzCDK4 to prevent the former from taking over the role of the latter in cancer cell proliferation,

A company that uses this approach isConcarlo Therapywhich is developing a new type of p27-based CDK inhibitor that helps regulate CDKs 2, 4, and 6.Dra. Stacy Blain, co-founder and scientific director of Concarlo Therapeutics, was one of the first to work on the study of the p27 protein and today is one of the world's leading experts in this area. He likens page 27 to a door; when it opens, CDKs are activated and allow cells, including cancer cells, to divide and multiply. When p27 closes, CDKs are inhibited, helping to minimize cell spreading. A healthy body performs this regulation naturally.

(Video) Hormone Receptor-Positive Advanced Breast Cancer: Challenges and New Treatment Options

Concarlo Therapeutics aims to develop a cancer treatment that builds on the natural, healthy function of p27: using it to inhibitBothCDK2 and 4 and slow the spread of cancer, starting with breast cancer and potentially progressing to endometrial, ovarian, pancreatic and non-small cell lung cancer. The company's peptide product is encapsulated in a lipid shell that protects the peptide from degradation as it travels to the tumor site. As p27 naturally inhibits CDK4 and CDK2 more than CDK1 or any other essential protein, the approach using this protein is more specific and less toxic than other CDK2-centric drugs.

As noted by Dr. Blain, the ultimate goal of cancer treatments, including Concarlo, is to create "drugs that give you better, longer days." In other words, drugs with less toxicity than previous - or current - options may give patients more and better quality time than they otherwise might have. Particularly for patients with endometrial and ovarian cancer, this extra time has another advantage: the ability to make an informed decision - rather than a rushed impulsive decision - about treatment options that may affect your reproductive health andlater mental health.

Raise health awareness:

One was published in 2013testwas entitled 'Making decisions about breast cancer care: are we asking too much of patients'? It turns out that "health literacy'Issues' - the individual's ability to find, understand and use information to guide health care decisions and adherence to treatment recommendations - were more common among cancer patients who felt they had too much or too little responsibility for their decisions of treatment.

10 years later like a cancerromancesEUcostscontinue to grow, innovative companies like Concarlo Therapeuticstheir ushelp increase potential treatment options and positive outcomes for patients. The next step, however, is to understand these options and potential outcomes for yourself: whether they are scientists working for the National Institutes of Health (NIH) to leverage and use funding for cutting-edge researchbiomedical researchor simply people who may have cancer in some form. After all,40%adults in the United States will be diagnosed with cancer at some point in their lives. Knowing the pros, cons and science behind treatments like CDK inhibitors can help these people improve their healthEUhealth awareness, overcome any confusion or misunderstanding they may encounter, and make informed health decisions for the future - as easily as they would wear pink today or identify a breast cancer awareness ribbon.


Why are CDK inhibitors important? ›

The main function of these inhibitors is to block cell cycle and inhibit cell proliferation by inhibiting the CDK enzyme activity. However, the first-generation of pan-CDK inhibitors have poor selectivity and high toxicity, leading to inevitable harmful effects on normal cells.

Are CDK inhibitors good for cancer treatment? ›

CDK4/6 inhibitors are a class of medicines used to treat certain types of hormone receptor-positive, HER2-negative breast cancer. These medicines interrupt the process through which breast cancer cells divide and multiply.

What are the side effects of cdk1 inhibitors? ›

Neutropenia is temporary and dose-dependent with the white blood count usually return to normal with dose-interruption or dose-reduction of the drug. Other side effects include diarrhea, fatigue, nausea, and alopecia (hair loss), which are usually mild and reversible by reducing the dose and taking regular breaks.

What are the side effects of CDK4 inhibitors? ›

The CDK4/6 inhibitors as a class are generally well tolerated. The most common class-wide adverse effects include nausea, diarrhea, fatigue, neutropenia, leukopenia, anemia, and thrombocytopenia.

What is a CDK inhibitor? ›

A substance being studied in the treatment of some types of cancer. CDK inhibitor AT7519M blocks enzymes needed for cells to divide. It is a type of cyclin-dependent kinase inhibitor. Also called AT7519M.

What are CDK inhibitors? ›

A CDK (cyclin-dependent kinase) inhibitor is any chemical that inhibits the function of CDKs. They are used to treat cancers by preventing overproliferation of cancer cells.

How does CDK affect cancer? ›

The expression of CDKs is controlled by a complex regulatory network comprised of genetic and epigenetic mechanisms, which are dysregulated during the progression of cancer. The abnormal activation of CDKs results in uncontrolled cancer cell proliferation and the induction of cancer stem cell characteristics.

What role do CDKs play in cancer? ›

Cyclin-dependent kinases (cdks) are critical regulators of cell cycle progression and RNA transcription. A variety of genetic and epigenetic events cause universal overactivity of the cell cycle cdks in human cancer, and their inhibition can lead to both cell cycle arrest and apoptosis.

Are CDK inhibitors chemotherapy? ›

Antineoplastic CDK inhibitors are used to treat conditions such as: Breast cancer. Chemotherapy-induced myelosuppression (most common dose-limiting and potentially fatal complication of cancer treatment)

What are the side effects of CDK? ›

Common side effects include fatigue and gastrointestinal disturbances, such as nausea, diarrhea, and vomiting. Bone marrow suppression resulting in neutropenia and leukopenia may also occur, although anemia and thrombocytopenia are less common.

What would happen if you treated blood stem cells with a CDK inhibitor? ›

Therefore, in vivo treatment with a CDK1 inhibitor decreases the formation of stem cell-derived tumors.

What is the mechanism of action of CDK inhibitors? ›

The canonical mechanism underlying CDK4/6 inhibitor activity is the suppression of phosphorylation of the retinoblastoma tumor suppressor protein, which serves to prevent cancer cell proliferation.

Is Verzenio better than Ibrance? ›

It is not known if Verzenio is better than Ibrance. They are similar treatments which have not been compared in head-to-head trials, although one trial is currently underway comparing the effects of Ibrance and Verzenio with an aromatase inhibitor and other medications in the treatment of breast cancer.

Which CDK4 6 inhibitor is better? ›

Abemaciclib has a different chemical structure and exhibits the highest inhibitory effect on CDK4/6 with a CDK4:CDK6 inhibition ratio of 5, and additional activity on multiple kinases5.

What is the overall survival of CDK4 6? ›

In the Kaplan–Meier analysis, OS rate at 3 years after first-line treatment initiation was 73.0% for ET+CDK4/6 inhibitor versus 49.1% for ET alone (log-rank p < . 0001).

Is CDK a tumor suppressor? ›

The cyclin-dependent kinase (CDK) inhibitor p27kip1 (CDKN1B) is known to be a tumor suppressor, however, it may also function as an oncogene within the cytoplasm by affecting cell motility and metastasis.

Which CDK inhibitors are FDA approved? ›

CDK 4/6 inhibitors in combination with hormonal therapy (aromatase inhibitor or fulvestrant) are FDA-approved for the first- or second-line treatment of patients with hormone receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative advanced or metastatic breast cancer.

What are the 4 types of CDK? ›

Classical cell cycle CDKs - Cdk4, Cdk6, Cdk2 and Cdk1 - regulate the transitions through the different phases of the cell-division cycle.

Why is CDK used? ›

CDKs are a family of multifunctional enzymes that can modify various protein substrates involved in cell cycle progression. Specifically, CDKs phosphorylate their substrates by transferring phosphate groups from ATP to specific stretches of amino acids in the substrates.

What does CDK stand for? ›

Cyclin-dependent kinases (CDKs) are involved in many crucial processes, such as cell cycle and transcription, as well as communication, metabolism, and apoptosis.

Does CDK inhibit the cell cycle? ›

First, it stops the cell cycle at the G 1​start subscript, 1, end subscript checkpoint by triggering production of Cdk inhibitor (CKI) proteins. The CKI proteins bind to Cdk-cyclin complexes and block their activity (see diagram below), buying time for DNA repair.

What role do inhibitors play in cancer formation? ›

Angiogenesis inhibitors are unique cancer-fighting agents because they block the growth of blood vessels that support tumor growth rather than blocking the growth of tumor cells themselves.

How are cell cycle inhibitors related to cancer? ›

Cell cycle checkpoints are essential to halt cell cycle progression in response to DNA damage, thereby allowing time for DNA repair. Inhibition of CHK1 or WEE1 in cancer cells prevents cell cycle arrest during S or G2 phase and enables cell proliferation despite accumulation of DNA damage.

What are inhibitors for cancer treatment? ›

Checkpoint inhibitors are a type of immunotherapy. They are a treatment for cancers such as melanoma skin cancer and lung cancer. These drugs block different checkpoint proteins. You might also hear them named after these checkpoint proteins – for example, CTLA-4 inhibitors, PD-1 inhibitors and PD-L1 inhibitors.

What is the role of CDKs quizlet? ›

What role do they play in the cell cycle? Cdk = cyclin dependent protein kinase. This is a serine/threonine kinase enzyme that will create a wide range of phosphorylation events in the cell that correlate with the cell cycle. The activity of cyclin dependent protein kinase is regulated by cyclin molecules.

What is the function of CDKs How are they activated? ›

CDKs are a family of related proteins that bind to specific cyclin proteins to form active complexes that can phosphorylate specific target molecules. CDKs play a critical role in cell replication, and different CDKs are sequentially activated and inactivated during G1, S, and M phases of the cell cycle.

What do CDKs partner with? ›

CDKs and cyclins in the cell cycle

In mammalian cells, CDK1, with its partners cyclin A2 and B1, alone can drive the cell cycle.

Where do CDK inhibitors bind? ›

Most CDK inhibitors have been developed to target the ATP binding pocket.

What drugs are CDK4 inhibitors? ›

The CDK4/6 inhibitors used to treat metastatic breast cancer are:
  • Abemaciclib (Verzenio)
  • Palbociclib (Ibrance)
  • Ribociclib (Kisqali)

What does HER2 positive stand for? ›

A positive test for HER2 means breast cancer may grow quickly and possibly come back (recur). This risk is significantly lowered with appropriate treatment. At the Abramson Cancer Center, we treat HER2-positive breast cancer with medications that work to slow or stop tumor growth.

What are inhibitors and why are they important? ›

Inhibitors are chemical or biological molecules that regulate chemical reactions by slowing down or blocking them from occurring. Inhibitors often work to slow or stop enzymes — proteins that catalyze reactions.

What are the main functions of the CDK complex? ›

CDK/cyclin complexes are best known to promote cell cycle progression in the mitotic cell cycle but are also crucial for important cellular processes not strictly associated with cellular division.

What is the significance of inhibitor constant? ›

The inhibitor constant, Ki, is an indication of how potent an inhibitor is; it is the concentration required to produce half maximum inhibition. Plotting 1/v against concentration of inhibitor at each concentration of substrate (the Dixon plot) gives a family of intersecting lines.

What is the importance of an inhibitor in order to produce a reaction? ›

They bind to the active site of enzymes and decrease their compatibility with substrates which causes the inhibition of the Enzyme-Substrate complexes formation. Consequently preventing the production of products by decreasing the catalysation of the reaction.

What are the benefits of inhibitor? ›

Corrosion inhibitor extend the lifespan of the equipment up to 250% Reduces the cost of repair due to corrosive damage. If the equipment is protected, service interruptions and operation malfunction can be avoided. For companies having corrosion inhibitor equipments, can avoid legal and environmental liabilities.

What are inhibitors used to prevent? ›

About Inhibitors

These treatment products improve blood clotting, and they are used to stop or prevent a bleeding episode.

What are the effects of inhibitors? ›

Inhibitors. Enzyme inhibitors are compounds which modify the catalytic properties of the enzyme and, therefore, slow down the reaction rate, or in some cases, even stop the catalysis. Such inhibitors work by blocking or distorting the active site.

What is the benefit of CDK? ›

AWS CDK enables you to define your infrastructure with code and provision it through AWS CloudFormation. You get all the benefits of CloudFormation, including repeatable deployment, easy rollback, and drift detection.

What is the most important regulator of CDK activity? ›

CDKs are positively regulated by CDK-activating kinases (CAKs) and are negatively regulated by CDK-inhibitors (CKIs). Among the CAKs, CDK20, also previously known as cell cycle-related kinase (CCRK) [6], has been reported to have CAK activity for CDK2 to promote the transition from G1 to S phase.

Why the inhibitor has decreased the maximum rate of reaction? ›

Allosteric inhibitors, however, decrease the maximum velocity because the enzymatic activity will decrease with the addition of the allosteric inhibitor no matter how high the concentration of the substrate is.

How do you determine the inhibition constant? ›

The inhibition constant Ki in the common case of competitive inhibition can be obtained by simple comparison of progress curves in the presence and in the absence of inhibitor. The difference between the times taken for the concentration of substrate to fall to the same value is used to obtain Ki.

What happens when inhibitor concentration increases? ›

At low concentrations of substrate, the inhibitor competes for the enzyme effectively, but at high concentrations of substrate, the inhibitor will have a much reduced effect, since the substrate outcompetes it, due to its higher concentration (remember that the inhibitor is at fixed concentration).

How is the effect of inhibitor overcome? ›

Competitive inhibition can be reversed by increasing the substrate concentration. If the substrate predominates in the mixture, it will tend to displace the inhibitor bound to the enzyme.

Do inhibitors slow down the reaction or prevent them from occuring? ›

Answer and Explanation: Inhibitors slow down chemical reactions by forcing those reactions to use a mechanism which has a higher activation energy. A high activation energy slows down a reaction because fewer molecules have sufficient energy to react and this results in a smaller number of collisions being successful.

How do inhibitors work to prevent an enzyme from functioning? ›

Enzyme inhibitors act by blocking or slowing enzymatic function, significantly reducing the capacity to convert substrates into products . Some inhibitors prevent enzymes from recognizing or binding to substrates, either by masking the substrate or by blocking the active-site on the enzyme. (Competitive inhibition).


(iRise Above Foundation)
2. Part 2 - Session 1 - CDK 4/6 Inhibitors in breast cancer: will they have a Large role in future?
3. Novel Breast Cancer Therapies: CDK4/6 Inhibitors
(i3 Health)
4. Expert Perspectives: CDK 4/6 Inhibitor Therapy for ER+ Metastatic Breast Cancer
(HMP Education)
5. The Changing Face of Advanced Prostate Cancer Webcast (2023)
6. ATLAS and CDK4/6 inhibitor trials presented by Dr. John Smith II, Compass Oncology
(Compass Oncology)


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