# Role of polo like kinase 4 in melanomagenesis and melanoma progression

> **NIH VA I01** · WM S. MIDDLETON MEMORIAL VETERANS HOSP · 2020 · —

## Abstract

SUMMARY:
 Melanoma is one of the most aggressive human cancers with approximately 87,110 new melanoma cases
and 9,730 melanoma-related deaths predicted in the U.S. in 2017. Further, melanoma is a significant problem
in Veterans. The US military currently is and has been engaged, in missions all over the world, including
recently, in the Middle East (Iraq and Afghanistan). Many US military personnel, who are deployed to high
ultraviolet (UV) index climates in tropical and subtropical zones are potentially at a higher risk for melanoma.
Further, these personnel are not adequately protected because they possibly have survival priorities other than
avoiding UV exposure. Based on the Veterans Affairs Central Cancer Registry (VACCR), melanoma is among
the five most frequently diagnosed cancers among VA cancer patients.
 Unfortunately, the available therapeutic strategies have either failed to achieve >25% response or the
responses are short-lived with developing resistance to therapy. Indeed, recent advances in the understanding
of melanoma biology has led to the development of targeted therapies such as BRAF inhibitors (vemurafenib
and dabrafenib) achieved improvement over chemotherapy for melanomas with BRAF-mutations. However,
even with these new targeted approaches, most of the patients develop resistance, thereby failing to achieve
lasting tumor regression. Therefore, further research is needed to understand the mechanism of melanoma
development and progression. Polo-like kinase 4 (PLK4), a serine/threonine kinase, is the master regulator of
centriole duplication. PLK4 is a low abundance suicidal kinase that is known to autophosphorylate itself to
promote its own destruction to limit centriole duplication once per cell cycle. Based on recent research, PLK4 is
emerging as a potential target for cancer treatment. PLK4 has been suggested to be involved in certain
cancers. Interestingly, overexpression of PLK4 has been shown to result in supernumerary centrosomes and
loss of primary cilia in transgenic mice and gastric cancer cells. Importantly, primary cilia exist in melanocytes
and frequently lost in melanoma. Although limited information is available regarding the potential role of PLK4
in certain cancers, its involvement in melanoma development and progression has not been evaluated. In our
preliminary data, we have found that PLK4 is overexpressed in melanoma cells and human tissues (in a limited
number of specimens studied) and its inhibition via a small molecule inhibitor centrinone B results in a
significant anti-proliferative response in multiple human melanoma cell lines. Thus, based on available
literature and our preliminary data, we propose to test the hypothesis that PLK4 plays a critical role in
melanoma development and progression and could serve as a novel target for melanoma management. The
following specific aims are proposed; 1) to define the role of PLK4 in melanoma development and progression,
employing a tissue microarray (TMA) ...

## Key facts

- **NIH application ID:** 9815339
- **Project number:** 5I01BX004221-02
- **Recipient organization:** WM S. MIDDLETON MEMORIAL VETERANS HOSP
- **Principal Investigator:** Nihal Ahmad
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-10-01 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9815339

## Citation

> US National Institutes of Health, RePORTER application 9815339, Role of polo like kinase 4 in melanomagenesis and melanoma progression (5I01BX004221-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9815339. Licensed CC0.

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