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What is the role of cell cycle control in cancer? ​

Abstract ​

The cell cycle is a fundamental biological process that governs cell growth, division, and death, and its regulation is crucial for maintaining genomic integrity. Dysregulation of cell cycle control is a hallmark of cancer, leading to uncontrolled cell proliferation and tumorigenesis. This review explores the multifaceted relationship between cell cycle control and cancer, emphasizing the roles of key regulatory proteins such as cyclins, cyclin-dependent kinases (CDKs), and tumor suppressors. We highlight the significance of cell cycle checkpoints, particularly the G1/S and G2/M transitions, in maintaining genomic stability and preventing tumorigenesis. Dysregulation at these checkpoints can result in genomic instability, a characteristic feature of cancer cells. The review also discusses the therapeutic implications of targeting cell cycle regulators, particularly CDK inhibitors, in cancer treatment. While these therapies have shown promise, challenges such as resistance and variability in patient response remain. Furthermore, the intersection of cell cycle regulation and metabolic pathways presents novel opportunities for therapeutic intervention. By synthesizing recent research findings, this review aims to provide a comprehensive understanding of the critical role of cell cycle control in cancer biology and underscores the importance of ongoing research in this area to advance cancer treatment strategies.

Outline ​

This report will discuss the following questions.

  • 1 Introduction
  • 2 The Cell Cycle: Overview and Phases
    • 2.1 Phases of the Cell Cycle
    • 2.2 Key Regulatory Proteins
  • 3 Cell Cycle Checkpoints and Their Role in Cancer
    • 3.1 G1/S Checkpoint
    • 3.2 G2/M Checkpoint
  • 4 Dysregulation of Cell Cycle Control in Cancer
    • 4.1 Oncogenes and Tumor Suppressors
    • 4.2 Genetic and Epigenetic Alterations
  • 5 Therapeutic Implications of Targeting Cell Cycle Regulators
    • 5.1 Current Treatments and Limitations
    • 5.2 Future Directions in Cancer Therapy
  • 6 Conclusion

1 Introduction ​

The cell cycle is a fundamental biological process that regulates cell growth, division, and death, ensuring the proper development and maintenance of multicellular organisms. The orderly progression through the cell cycle is orchestrated by a complex network of regulatory proteins, including cyclins and cyclin-dependent kinases (CDKs), which facilitate transitions between distinct phases of the cycle. Dysregulation of these mechanisms is a hallmark of cancer, leading to uncontrolled cell proliferation and tumorigenesis. As such, understanding the role of cell cycle control in cancer is crucial for elucidating the underlying mechanisms of malignancy and developing effective therapeutic strategies.

The significance of cell cycle regulation in cancer biology cannot be overstated. Alterations in cell cycle checkpoints, such as the G1/S and G2/M transitions, can lead to genomic instability, a key feature of cancer cells [1]. Moreover, the interplay between cell cycle regulators and metabolic pathways has emerged as an important area of study, as cancer cells often exhibit altered metabolism to meet the demands of rapid proliferation [2]. This intersection of cell cycle control and metabolism not only highlights the complexity of cancer biology but also presents novel opportunities for therapeutic intervention [3].

Current research has identified several critical components of cell cycle regulation that contribute to cancer progression. For instance, the retinoblastoma protein (pRb) and the E2F transcription factor family play pivotal roles in controlling the G1/S transition [4]. Additionally, various oncogenes and tumor suppressor genes, such as those encoding CDKs and their inhibitors, have been implicated in the dysregulation of cell cycle control [5]. Understanding these molecular interactions is essential for developing targeted therapies aimed at restoring normal cell cycle regulation in cancer cells.

The present review will systematically explore the multifaceted relationship between cell cycle control and cancer. We will begin with an overview of the cell cycle and its phases, highlighting key regulatory proteins that govern these processes. Subsequently, we will delve into the role of cell cycle checkpoints, specifically the G1/S and G2/M checkpoints, in maintaining genomic integrity and preventing tumorigenesis. We will also examine how dysregulation of these checkpoints contributes to cancer development, focusing on the roles of oncogenes and tumor suppressors, as well as genetic and epigenetic alterations that impact cell cycle control.

In the latter sections, we will discuss the therapeutic implications of targeting cell cycle regulators in cancer treatment. This includes an overview of current treatments, their limitations, and potential future directions for developing more effective cancer therapies. By synthesizing recent research findings, this review aims to provide a comprehensive understanding of the critical role of cell cycle control in cancer biology and underscore the importance of ongoing research in this area to advance cancer treatment strategies.

Through this exploration, we hope to illuminate the intricate relationship between cell cycle regulation and cancer, fostering a deeper understanding of how these processes can be manipulated for therapeutic benefit.

2 The Cell Cycle: Overview and Phases ​

2.1 Phases of the Cell Cycle ​

Cell cycle control plays a critical role in cancer development and progression, as the regulation of the cell cycle is fundamental to maintaining normal cellular functions such as growth, differentiation, and apoptosis. In cancer, dysregulation of the cell cycle machinery leads to uncontrolled cell proliferation, a hallmark of malignant transformation.

The cell cycle consists of several distinct phases: G1 (gap 1), S (synthesis), G2 (gap 2), and M (mitosis). Each phase is tightly regulated by a series of checkpoints and regulatory proteins, including cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors. Cyclins and CDKs form complexes that drive the cell through various phases of the cycle by phosphorylating target proteins, thereby facilitating transitions between phases. For instance, the G1/S checkpoint is crucial for assessing whether the cell is ready to replicate its DNA, while the G2/M checkpoint ensures that DNA is properly replicated and undamaged before mitosis begins[4].

In cancer cells, the mechanisms governing these transitions can become impaired. For example, mutations in genes encoding cyclins or CDKs can lead to their overexpression or constitutive activation, resulting in unchecked cell division. Furthermore, the loss of function of tumor suppressor proteins, such as the retinoblastoma protein (pRB), which normally inhibits progression from G1 to S phase, can further exacerbate this dysregulation[6]. As a result, cancer cells can bypass critical checkpoints, leading to genomic instability and increased mutation rates, which are characteristic of tumor cells[1].

The relationship between cell cycle regulation and cancer has also prompted the exploration of targeted therapies aimed at restoring control over cell proliferation. Inhibitors of CDKs, particularly CDK4/6 inhibitors, have shown promise in treating cancers such as breast cancer by re-establishing control over the cell cycle and inducing tumor cell apoptosis[5]. Additionally, other components of the cell cycle machinery, such as checkpoint kinases and the anaphase-promoting complex/cyclosome (APC/C), are being investigated as potential therapeutic targets[7].

Moreover, the interplay between cell cycle regulation and metabolic pathways has emerged as a significant area of research. Alterations in metabolic processes can influence cell cycle progression, with cancer cells often exhibiting enhanced glycolytic activity to meet the high energy demands associated with rapid proliferation[3]. This cross-talk between metabolism and the cell cycle suggests that targeting metabolic pathways may provide novel therapeutic avenues in cancer treatment[2].

In summary, cell cycle control is integral to the prevention of cancer, and its dysregulation is a key feature of tumorigenesis. Understanding the molecular mechanisms underlying cell cycle regulation not only elucidates the pathogenesis of cancer but also highlights potential therapeutic strategies aimed at re-establishing control over cellular proliferation.

2.2 Key Regulatory Proteins ​

The role of cell cycle control in cancer is pivotal, as it directly relates to the mechanisms underlying cellular proliferation and the maintenance of genomic stability. Dysregulation of the cell cycle is a hallmark of cancer, contributing to uncontrolled cell growth and tumor progression. The cell cycle is a tightly regulated process that ensures cells divide only when conditions are favorable and necessary for tissue growth and repair. Central to this regulation are cyclin-dependent kinases (CDKs) and their regulatory partners, cyclins, which facilitate transitions between different phases of the cell cycle.

Cell cycle regulators, including CDKs, cyclins, and checkpoint kinases, play crucial roles in controlling cell cycle progression. When activated, CDKs promote the transition from one phase of the cell cycle to another, enabling cells to move from the G1 phase to the S phase, and subsequently to the G2 and M phases. This process is governed by a series of checkpoints that assess whether the cell is ready to proceed to the next phase, ensuring that any DNA damage or other cellular stresses are addressed before division occurs [2][5].

In cancer, the mechanisms that regulate the cell cycle often become disrupted. For instance, the loss of function of tumor suppressor proteins, such as p53 and retinoblastoma protein (pRB), can lead to unchecked activation of CDKs, resulting in aberrant cell proliferation. Cancer cells often exhibit genomic instability, a consequence of failed cell cycle checkpoints, which can further drive tumor evolution and heterogeneity [5][8].

The therapeutic implications of targeting cell cycle regulation in cancer are significant. Inhibitors of CDKs, such as palbociclib, have shown promise in treating various malignancies, including breast cancer. These inhibitors work by halting the cell cycle at specific points, thereby preventing cancer cells from proliferating. The effectiveness of CDK inhibitors is particularly evident in estrogen receptor-positive breast cancer, where they can enhance the effects of other therapies, such as aromatase inhibitors [8][9].

Moreover, the interplay between cell cycle regulation and cellular metabolism has emerged as a critical area of research. Cancer cells often exhibit metabolic reprogramming that supports their rapid proliferation, with key regulatory proteins linking metabolic pathways to cell cycle control. This connection suggests that therapeutic strategies targeting both the cell cycle and metabolic adaptations may provide new avenues for cancer treatment [3][10].

In summary, the regulation of the cell cycle is integral to maintaining normal cellular function and preventing tumorigenesis. The dysregulation of cell cycle control mechanisms is a defining feature of cancer, making it a crucial target for therapeutic intervention. As research progresses, a deeper understanding of the cell cycle and its regulatory proteins may lead to more effective cancer treatments that can improve patient outcomes.

3 Cell Cycle Checkpoints and Their Role in Cancer ​

3.1 G1/S Checkpoint ​

Cell cycle control plays a critical role in cancer development and progression, primarily through the regulation of checkpoints that ensure the proper sequence and fidelity of cell cycle events. Among these checkpoints, the G1/S checkpoint is particularly significant, as it serves as a pivotal restriction point where the cell decides whether to commit to DNA replication and subsequent division.

The G1/S checkpoint is governed by various proteins, including the retinoblastoma protein (pRb) and cyclin-dependent kinases (CDKs). In normal cells, this checkpoint prevents cells with DNA damage from proceeding to the S phase, thereby allowing time for DNA repair and maintaining genomic stability. However, in many cancers, mutations in genes encoding checkpoint proteins lead to a loss of control at this stage, resulting in genetic instability, a hallmark of cancer (Weinert and Lydall 1993; Molinari 2000).

Mutations in the p53 tumor suppressor gene, which is crucial for the G1/S checkpoint function, are particularly prevalent in human tumors. In cells with p53 mutations, the G1 checkpoint is often dysfunctional, leading to unchecked progression into the S phase, even in the presence of DNA damage. Consequently, these cells rely on the G2/M checkpoint for repair and survival (Koniaras et al. 2001; Damia and Broggini 2004). The G2/M checkpoint, regulated by proteins such as checkpoint kinase 1 (Chk1), monitors DNA integrity before the cell enters mitosis. Inhibiting this checkpoint in p53-deficient cells can induce cell death, making it a potential target for cancer therapies (Bucher and Britten 2008; Kuntz and O'Connell 2009).

Moreover, the dysregulation of the G1/S transition is implicated in the over 90% of melanoma cases, where the tumor cells predominantly depend on the G2/M checkpoint to halt the cell cycle for DNA repair. Targeting the G2/M checkpoint in conjunction with the G1/S transition has been proposed as a strategy for synthetic lethality, exploiting the vulnerabilities of cancer cells lacking functional G1/S checkpoints (Barnaba and LaRocque 2021).

In summary, the integrity of cell cycle checkpoints, particularly the G1/S checkpoint, is crucial for preventing the onset of cancer. Defects in these regulatory mechanisms lead to genetic instability and promote tumorigenesis, highlighting the importance of understanding these pathways for developing effective cancer therapies. Inhibiting checkpoint proteins like Chk1 may enhance the efficacy of existing treatments by exploiting the inherent weaknesses of cancer cells, thereby improving patient outcomes (Ashwell and Zabludoff 2008; Carrassa and Damia 2011).

3.2 G2/M Checkpoint ​

Cell cycle control plays a crucial role in maintaining genomic integrity and preventing cancer progression. The cell cycle is regulated by checkpoints, which are mechanisms that ensure proper progression through the different phases of the cell cycle, particularly in response to DNA damage. Among these checkpoints, the G2/M checkpoint is particularly significant due to its role in preventing cells from entering mitosis with damaged DNA, thereby allowing time for DNA repair.

The G2/M checkpoint acts as a quality control mechanism that halts the cell cycle when DNA damage is detected. This checkpoint is essential for ensuring that cells do not propagate genetic defects to daughter cells. In normal cells, this checkpoint is robust, providing an opportunity to repair DNA damage before proceeding to mitosis. However, in many cancer cells, the G2/M checkpoint is often compromised, which can lead to increased genomic instability and tumorigenesis (Molinari 2000; Kuntz & O'Connell 2009).

Research has shown that defects in cell cycle checkpoints, including the G2/M checkpoint, are associated with an increased risk of various cancers. For instance, a case-control study demonstrated that a less efficient G2/M checkpoint was significantly associated with lung cancer risk in African American women, highlighting the importance of this checkpoint in cancer susceptibility (Zheng et al. 2010). Similarly, another study indicated that deficiencies in the G2/M checkpoint could lead to increased lung cancer risk, suggesting that these checkpoints may serve as potential biomarkers for cancer susceptibility (Xing et al. 2007).

The G2/M checkpoint is regulated by several key proteins, including the serine/threonine kinase Chk1, which is activated in response to DNA damage. Chk1 plays a vital role in inhibiting cyclin-dependent kinase 1 (CDK1), thus preventing the cell from entering mitosis with damaged DNA (Koniaras et al. 2001). In cancer cells, particularly those with mutations in the p53 tumor suppressor gene, the G2 checkpoint may become a critical survival pathway, allowing these cells to evade apoptosis despite the presence of DNA lesions (Rivas et al. 2024).

Targeting the G2/M checkpoint has emerged as a promising strategy in cancer therapy. Inhibitors of checkpoint proteins, such as Chk1, are being explored to enhance the effectiveness of DNA-damaging agents like chemotherapy and radiation therapy. By inhibiting the G2/M checkpoint, cancer cells may be forced into mitosis with unrepaired DNA, leading to cell death (Dillon et al. 2014; Bucher & Britten 2008). This approach exploits the reliance of cancer cells on the G2/M checkpoint for survival, particularly in the context of existing DNA damage.

In summary, the G2/M checkpoint plays a pivotal role in cancer biology by ensuring the fidelity of DNA replication and repair. Deficiencies in this checkpoint are associated with increased cancer risk and provide potential therapeutic targets to enhance cancer treatment efficacy. By understanding the mechanisms underlying G2/M checkpoint regulation and its implications in cancer, researchers can develop more effective strategies for cancer therapy.

4 Dysregulation of Cell Cycle Control in Cancer ​

4.1 Oncogenes and Tumor Suppressors ​

Dysregulation of cell cycle control is a hallmark of cancer, contributing to the uncontrolled proliferation of tumor cells. The cell cycle, which consists of distinct phases (G1, S, G2, and M), is tightly regulated by a network of cyclins, cyclin-dependent kinases (CDKs), and their inhibitors. In normal cells, the progression through these phases is regulated by various signals that ensure proper growth and division. However, in cancer cells, this regulation is often disrupted, leading to aberrant cell proliferation and tumorigenesis.

One critical aspect of cell cycle dysregulation in cancer is the alteration of oncogenes and tumor suppressor genes. Oncogenes are mutated or overexpressed versions of normal genes that promote cell division and survival. For instance, mutations in growth signaling pathways can hyperactivate these oncogenes, leading to unchecked cell proliferation. Conversely, tumor suppressor genes, which normally function to inhibit cell division or promote apoptosis, may be inactivated through mutations or epigenetic changes. This loss of function removes critical checks on the cell cycle, allowing cancer cells to bypass regulatory mechanisms that would typically halt their proliferation in response to DNA damage or other cellular stressors [11].

Cyclin-dependent kinases (CDKs) play a pivotal role in the control of the cell cycle. They are activated by binding to cyclins and are responsible for driving the cell cycle forward. In breast cancer, for example, dysregulation of CDKs has been associated with aggressive tumor behavior and poor prognosis. Inhibitors targeting CDKs have emerged as potential therapeutic agents, demonstrating efficacy in modulating the cell cycle and inhibiting tumor growth [8].

Furthermore, the dysregulation of the cell cycle is linked to genomic instability, a characteristic feature of cancer. This instability arises from the failure of cell cycle checkpoints that normally prevent cells with damaged DNA from progressing through the cycle. The loss of checkpoint function leads to the accumulation of genetic alterations, further driving tumor evolution and heterogeneity [12].

In addition to oncogenes and tumor suppressors, recent studies have highlighted the importance of cell cycle checkpoint kinases, such as ATM and CHK2, in cancer progression. Dysregulation of these checkpoint proteins can predispose individuals to specific cancer types and influence treatment resistance [13]. For instance, mutations in ATM have been associated with a higher incidence of certain breast cancer subtypes, while CHK2 dysregulation is linked to metastatic disease [13].

In summary, the role of cell cycle control in cancer is multifaceted, involving the interplay of oncogenes, tumor suppressors, and various regulatory proteins. The dysregulation of these components leads to unchecked cell proliferation, genomic instability, and ultimately contributes to cancer development and progression. Understanding these mechanisms not only elucidates the fundamental processes of tumorigenesis but also informs the development of targeted therapies aimed at restoring normal cell cycle regulation in cancer cells [7][11][12].

4.2 Genetic and Epigenetic Alterations ​

Dysregulation of cell cycle control is a fundamental characteristic of cancer, contributing significantly to the uncontrolled proliferation of cancer cells. This dysregulation is often driven by genetic and epigenetic alterations that affect the intricate network of regulatory proteins responsible for cell cycle progression.

The cell cycle is tightly regulated by cyclins and cyclin-dependent kinases (CDKs), which are essential for transitioning through various phases of the cycle. When these regulators are altered, it can lead to unchecked cell division, a hallmark of cancer. For instance, the abnormal activation of CDKs is associated with uncontrolled cancer cell proliferation and the induction of cancer stem cell characteristics, which further complicates treatment responses and disease progression [14]. Moreover, mutations in genes encoding cell-cycle regulatory proteins can lead to the loss of function of tumor suppressor proteins and hyperactivation of growth signaling networks, promoting oncogenic proliferation [11].

In breast cancer, the expression patterns of CDKs have been linked to tumor progression and metastasis. The aggressive nature of breast cancer, coupled with its heterogeneity and chemoresistance, underscores the urgent need for novel therapeutic targets aimed at CDKs to modulate cell cycle dynamics and inhibit tumor growth [8]. In addition, the regulation of cell cycle checkpoints, which are critical for maintaining genomic integrity, is often compromised in cancer. Defective checkpoint function can lead to genetic modifications that further drive tumorigenesis [12].

Epigenetic alterations also play a significant role in cell cycle dysregulation. These alterations can affect gene expression without changing the underlying DNA sequence, thereby influencing the levels of cyclins and CDKs. Such dysregulation can result in the loss of normal growth control mechanisms, allowing cells to bypass regulatory checkpoints that would normally halt the cell cycle in response to DNA damage or other stressors [7]. Furthermore, microRNAs have been identified as key regulators of the cell cycle, with their dysregulation contributing to cancer progression by modulating the expression of cyclins and CDKs [15].

In summary, the dysregulation of cell cycle control in cancer is a multifaceted process influenced by genetic mutations, epigenetic changes, and the aberrant expression of regulatory proteins. This dysregulation not only facilitates uncontrolled cell proliferation but also contributes to the genomic instability that characterizes cancer, thereby presenting significant challenges for effective treatment strategies. Understanding these mechanisms is crucial for developing targeted therapies that can effectively combat cancer by restoring normal cell cycle regulation.

5 Therapeutic Implications of Targeting Cell Cycle Regulators ​

5.1 Current Treatments and Limitations ​

Cell cycle control plays a pivotal role in cancer biology, as it is intricately linked to cellular proliferation, genomic stability, and tumor progression. The dysregulation of the cell cycle is a hallmark of cancer, leading to uncontrolled cell growth and the development of malignancies. Various components of the cell cycle machinery, including cyclins, cyclin-dependent kinases (CDKs), and their inhibitors, are frequently altered in cancerous cells, resulting in aberrant cell cycle progression and contributing to oncogenesis [12][14].

Therapeutically, targeting cell cycle regulators has emerged as a promising strategy in cancer treatment. Inhibitors of CDKs, particularly CDK4 and CDK6, have shown significant efficacy in treating hormone receptor-positive breast cancer. For instance, palbociclib, a selective CDK4/6 inhibitor, has been demonstrated to prolong progression-free survival when combined with aromatase inhibitors like letrozole in clinical settings [9]. The rationale behind this approach is that by inhibiting CDKs, the uncontrolled proliferation of cancer cells can be halted, thereby enhancing the effectiveness of existing therapies [7].

Current treatments targeting cell cycle regulators, such as CDK inhibitors, are gaining traction; however, they are not without limitations. One major challenge is the development of resistance to these therapies. Tumor cells may adapt to CDK inhibition through various mechanisms, including the upregulation of alternative pathways that promote survival and proliferation despite the presence of inhibitors [7]. Additionally, the effectiveness of these treatments can vary significantly among different cancer types and individual patients, necessitating a more personalized approach to therapy [14].

Moreover, while targeting the cell cycle has therapeutic potential, it is essential to consider the complex interplay between cell cycle regulation and other cellular processes, such as metabolism and apoptosis. For example, cell cycle regulators have been implicated in modulating metabolic pathways critical for cancer cell survival and growth, suggesting that a combination of therapies targeting both the cell cycle and metabolic pathways may enhance treatment efficacy [3].

In conclusion, cell cycle control is fundamental to cancer development and progression, and targeting its regulators represents a promising therapeutic avenue. However, the current treatments face challenges, particularly regarding resistance and variability in patient response. Future research should focus on overcoming these limitations through combinatorial strategies and personalized medicine approaches to optimize therapeutic outcomes for cancer patients.

5.2 Future Directions in Cancer Therapy ​

Cell cycle control plays a critical role in cancer, primarily because the dysregulation of the cell cycle is a hallmark of tumorigenesis. Normal cell cycle regulation is essential for maintaining genomic stability and ensuring proper cellular proliferation, growth, and differentiation. When this regulation is disrupted, it can lead to uncontrolled cell proliferation, genomic instability, and ultimately, cancer progression [12].

The cell cycle is governed by a complex interplay of cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors (CKIs). CDKs, in particular, are pivotal in driving the cell through various phases of the cycle. Alterations in the expression or activity of these proteins can result in the loss of normal cell-cycle control, which is frequently observed in many cancers, including breast and gastrointestinal cancers [9][16].

Therapeutically, targeting cell cycle regulators has emerged as a promising strategy in cancer treatment. Inhibitors of CDKs, such as palbociclib, have shown significant efficacy in breast cancer models, prolonging progression-free survival when combined with other therapies [9]. Moreover, the regulation of the cell cycle can influence the effectiveness of chemotherapy, with some strategies aiming to enhance the sensitivity of tumor cells to chemotherapeutic agents through cell cycle modulation [17].

Future directions in cancer therapy may involve the development of more selective CDK inhibitors and combination therapies that target multiple aspects of tumor biology, including metabolism and immune evasion. Understanding the intricate relationships between cell cycle regulation and other cellular processes, such as metabolism and immune response, is crucial for identifying novel therapeutic targets [18]. Additionally, recognizing the role of genetic and epigenetic alterations in CDK regulation could inform patient selection for targeted therapies, improving treatment outcomes [14].

In conclusion, cell cycle control is fundamentally linked to cancer biology, and the strategic targeting of cell cycle regulators offers a pathway for innovative therapeutic approaches. Continued research into the molecular mechanisms governing cell cycle dysregulation and its implications for cancer therapy will be essential for developing effective treatments that can overcome resistance and improve patient prognosis [7].

6 Conclusion ​

The exploration of cell cycle control in cancer reveals significant insights into the mechanisms underlying tumorigenesis and the potential for targeted therapies. Key findings indicate that dysregulation of cell cycle checkpoints, particularly the G1/S and G2/M transitions, is a hallmark of cancer, leading to uncontrolled cell proliferation and genomic instability. The interplay between oncogenes, tumor suppressors, and cell cycle regulators highlights the complexity of cancer biology and the challenges faced in developing effective treatments. Current therapeutic strategies, such as CDK inhibitors, have shown promise, yet resistance remains a critical hurdle. Future research should focus on combinatorial approaches that integrate targeting of cell cycle regulators with metabolic pathways and immune responses to enhance treatment efficacy. By deepening our understanding of cell cycle dysregulation, we can pave the way for innovative therapies that restore normal cellular function and improve patient outcomes.

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