Breakthrough Study Shows Plogosertib Potential for BTC Treatment

Plogging New Paths for Biliary Tract Cancer Treatment

- Biliary tract cancer (BTC) or cholangiocarcinoma is an aggressive tumor with poor prognosis -

KUALA LUMPUR, Malaysia — Cyclacel Pharmaceuticals, Inc. (NASDAQ: CYCC; NASDAQ: CYCCP), a dynamic biopharmaceutical company focused on pioneering cancer treatments, has spotlighted a preclinical study conducted by independent researchers. Titled, “Evaluation of antitumor effects of plogosertib, PLK1 inhibitor in biliary tract cancer with BUBR1 as a potential biomarker”, this study showcases findings from the journal, Cancer Research, initially presented at a significant cancer research gathering this year.

The study uncovered that several BTC cell lines demonstrated sensitivity to the compound plogosertib, both when used alone and in combination with other treatments. This aligns with plogosertib's role as an antimitotic agent, which promotes the formation of the mitotic checkpoint complex (MCC) during prometaphase. The end result? Induced mitotic arrest and subsequent apoptosis of malignant BTC cells.

BUBR1: A Potential Biomarker

Researchers also identified BUBR1, a vital protein for the mitotic checkpoint, as a possible biomarker that can help gauge the effectiveness of plogosertib. Notably, BTC cells exhibiting high levels of BUBR1 showed greater sensitivity to plogosertib than those with lower expressions. This crucial finding posits that BTC cells with elevated BUBR1 levels are more likely to respond positively to the PLK1 inhibitor, especially when paired with ATR inhibitors. This opens avenues for strategic combination therapies targeting PLK1 in treating BTC.

Understanding Biliary Tract Cancer

Biliary tract cancer (BTC), or cholangiocarcinoma, is a rare yet aggressive cancer affecting the biliary system, the intricate network connecting the liver, gallbladder, and small intestine. According to estimates from cancer health agencies, the annual incidence of BTC in the U.S. is around 4.4 cases per 100,000 people. Sadly, the prognosis for BTC patients remains grim, with approximately only 10-40% being alive five years post-surgery.

Treatment avenues for BTC can vary, including chemotherapy, surgery, radiation, and targeted therapies, depending on the stage of the disease and its location. Despite these strategies, effective cures are scarce, leading to an urgent need for innovative treatments for patients grappling with recurrent, refractory, or unresectable BTC.

Plogo's Mechanism: How It Works

The polo-like kinase 1 (PLK1) plays a crucial role in cell division. As a serine/threonine kinase, it is a key regulator involved in critical processes such as DNA damage response, spindle formation, and cell division. Cancer cells, particularly those mutated in KRAS or p53, exhibit heightened sensitivity to PLK1 depletion. Conversely, normal cells with functional cell cycle checkpoints show resilience against these treatments.

Plogosertib (formerly known as CYC140) stands out as a novel compounds that selectively inhibits PLK1. It has showcased remarkable efficacy in human tumor xenograft models without toxic side effects at the administered doses. Cyclacel’s commitment to advancing plogosertib in both solid tumors and leukemias is supported by encouraging preclinical evidence indicating effectiveness in cancers with specific mutations. Recent findings also hint at its potential effectiveness against KRAS-mutated colorectal cancer, elevating its profile in the oncology landscape.

Exciting Clinical Developments

Preliminary data from a Phase 1 clinical study of oral plogosertib illustrated excellent tolerability among participants, with no dose-limiting toxicities observed across five different dosing schedules. Clinical benefits were documented in patients battling various cancers, including adenoid cystic carcinoma, BTC, ovarian malignancies, and squamous cell cancers.

Cyclacel's Vision for the Future

Cyclacel is on a mission to innovate within the oncology sector. As a clinical-stage biopharmaceutical entity, it is dedicated to developing state-of-the-art cancer therapies grounded in cell cycle and mitotic biology. The firm is concentrating on its anti-mitotic program, assessing the efficacy of plogosertib in solid tumors and hematological cancers. With a robust pipeline featuring cutting-edge drug candidates, Cyclacel seeks to establish a diversified biopharmaceutical enterprise addressing key oncology and hematology indications.

For more details about Cyclacel’s development endeavors and product offerings, interested parties can visit www.cyclacel.com.

Frequently Asked Questions

What is Plogosertib and how does it work?

Plogosertib is a selective PLK1 inhibitor that induces apoptosis in cancer cells by causing prolonged mitotic arrest.

What is the significance of the BUBR1 protein?

BUBR1 serves as a potential biomarker for assessing the sensitivity of BTC cells to Plogosertib, helping to personalize treatment strategies.

What does the future hold for Cyclacel Pharmaceuticals?

Cyclacel aims to advance its pipeline of innovative cancer medicines that leverage understanding of cell cycle dynamics and mitotic processes.

What are the current treatment options for biliary tract cancer?

BTC treatment can include chemotherapy, surgery, radiation, and targeted therapies, though effective options for advanced cases are limited.

How has Plogosertib performed in clinical trials?

Phase 1 trials indicate that Plogosertib is well tolerated with promising clinical benefits noted in various types of cancers.

About The Author

Hi there, As a writer and financial specialist, Henry Turner is passionate about guiding people through the complex world of finance. Having worked in finance for many years, I am an expert at simplifying difficult financial ideas into understandable, useful insights for my blog and articles. My goal is to arm you with the confidence and information you need to make wise financial choices.

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