The Role of CDKs in Breast Cancer Among Women in Pakistan

Researchers examined the mRNA expression levels of six CDKs in Pakistani women with pre- and postmenopausal breast cancer with lung metastasis.

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Breast cancer (BC) affects Pakistani women at a higher rate compared to women in other Asian countries. What is more concerning is that the incidence of BC in younger women (pre-menopausal), BC metastasis and BC mortality are also disproportionately high in Pakistan. Causes of this inordinate plight for Pakistani women are not fully understood, however, researchers postulate that a lack of facilities, a delay in seeking medical attention, a conservative society, or religious beliefs against discussion of such topics may have causal roles in this discrepancy. 

“According to a survey conducted in Karachi [Pakistan], the average incidence of BC presentation was 27.4% between the age[s] of 25-37 years, which was highest compared to other cancer presentation age groups [8]. As to why the rates of pre-menopausal breast cancer in Pakistan are so high is not yet known.”

Human epidermal growth factor receptor 2 positive (HER2+) breast cancer is a common and aggressive subtype of BC that is prone to metastasis. At advanced stages, patients can become unresponsive to currently available treatment regimens—sadly leading to mortality. This problem indicates an important need to identify new therapeutic strategies that halt the progression of this disease. Researchers are interested in potentially accomplishing this task by targeting transcriptional elements in the cell cycle called cyclin-dependent kinases (CDKs).

“Defects in cell cycle and transcription regulation phases which are governed by cyclin-dependent kinases (CDKs) are the hallmark of many cancers that underpin the progression of the disease.”

The Study

Recently, researchers Muhammad Fazal Hussain Qureshi, Muzna Shah, Mahira Lakhani, Zain Jawed Abubaker, Danish Mohammad, Hira Farhan, Iman Zia, Rida Tafveez, Samahir Tariq Khan, Rubina Ghani, Shamim Mushtaq, and Ghulam Haider from Ziauddin University, Sohail University and Jinnah Postgraduate Medical Center examined the mRNA expression of six cyclin-dependent kinases (CDK11, CDK12, CDK17, CDK18, CDK19, and CDK20) in early stage (II) and advanced stage (III and IV) pre- and postmenopausal BC patients with lung metastasis. The majority of these patients were HER2+. On February 10, 2021, their researcher paper was published in Genes & Cancer’s Volume 12, and entitled, “Gene signatures of cyclin-dependent kinases: a comparative study in naïve early and advanced stages of lung metastasis breast cancer among pre- and post-menopausal women.”

The researchers obtained blood samples from lung metastasis breast cancer patients at Ziauddin Hospital and Jinnah Postgraduate Medical Center in Karachi, Pakistan. Out of 250 BC patients, 150 were pre-menopausal (mean age 30 ± 3.8) and 100 were postmenopausal (mean age 45 ± 2.8). A total of 200 pre- and postmenopausal lung metastasis BC and healthy control blood samples were taken for RNA isolation. The team used quantitative PCR to measure CDKs mRNA expressions. 

Results & Conclusion

The researchers found that CDK11, CDK12, CDK17, CDK18, and CDK19 were all overexpressed in both pre- and postmenopausal groups. Their results showed that CDK20 was progressively downregulated from early to advanced stages in both groups of patients. Interestingly, CDK20 was highly expressed only among the advanced stage (IV) pre-menopausal BC patients compared to the postmenopausal BC patients. Overall, this study found more evidence to suggest that CDKs overexpression may predict BC progression. Their research results provide an additional rationale for investigating the use of CDKs in new anticancer strategies to treat HER2+ BC cancers.

“Taken together, clinical studies on CDKs inhibitors, are needed to investigate the role of these CDKs in advanced stages HER2+ BC patients. Furthermore, clinical trials will also clarify whether these CDKs will become targets for the treatment of metastatic HER2+BC patients.”

Click here to read the full research paper, published by Genes & Cancer.

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