Ribosome Biogenesis & Cancer Development
Definition of Ribosome Biogenesis (RiBi)
RiBi is a remarkably complex and energetically demanding process. It involves the coordinated synthesis of four ribosomal RNA (rRNA) species (18S, 5.8S, 28S/25S rRNAs transcribed by RNA Polymerase I as a single polycistronic precursor, and the 5S rRNA transcribed by RNA Polymerase III) and approximately 80 ribosomal proteins (RPs). This multi-stage pathway commences in the nucleolus with rRNA transcription and extensive processing, involving endo- and exonucleolytic cleavages, chemical modifications guided by small nucleolar RNAs (snoRNAs), and folding. RPs are imported into the nucleolus to assemble with pre-rRNA, forming preribosomal particles that undergo further maturation steps in the nucleoplasm and cytoplasm before becoming translationally competent 40S and 60S subunits. The sheer scale of this operation underscores its importance.
Fig.1 Screen setup to identify novel ribosome biogenesis inhibitors.1
Dysregulation of RiBi in Cancer
Uncontrolled proliferation, a defining characteristic of cancer, places an enormous demand on the cell's protein synthesis capacity. Cancer cells must continuously produce proteins for growth, division, invasion, and adaptation to stressful microenvironments. This necessitates a persistently upregulated RiBi pathway. The enlarged nucleoli often seen in cancer cells are a morphological testament to this heightened activity.
- Upregulation of RiBi in Cancer
Elevated RiBi is not restricted to a few cancer types but is a pervasive feature observed across a wide spectrum of human malignancies. This isn't merely a secondary effect of rapid division but an actively driven process, integral to the malignant phenotype.
- RiBi in Cancer Stemness
The influence of dysregulated RiBi extends beyond merely fueling proliferation. Evidence suggests it plays a role in maintaining cancer stem cell (CSC) populations, which are critical for tumor initiation, relapse, and therapy resistance. Moreover, modifications in RiBi have been associated with the epithelial-mesenchymal transition (EMT), a biological process that confers cancer cells with migratory and invasive capabilities, which are pivotal for metastasis.
Applications of RiBi Research
Understanding and targeting RiBi in cancer has several critical applications for drug discovery and development. Creative Biolabs's services can empower your research in the following areas:
- Novel Therapeutic Target Identification and Validation
Uncover and confirm new molecular targets within the RiBi pathway that are essential for cancer cell survival and proliferation in specific tumor types. This includes identifying key enzymes, regulatory proteins, or steps in rRNA processing that can be selectively inhibited.
- Mechanism of Action (MoA) Elucidation
Determine if your novel or existing anticancer agents exert their effects by disrupting RiBi. Our detailed analyses can pinpoint specific points of interference, such as inhibition of RNA Polymerase I, impaired pre-rRNA processing, or induction of nucleolar stress.
- Drug Discovery Support & Candidate Prioritization
Screen and evaluate the efficacy of new chemical entities or biologicals designed to modulate RiBi. We provide robust data to help prioritize lead candidates for further preclinical and clinical development, including assessment of specificity and therapeutic window.
- Biomarker Development for Prognosis
Identify components of the RiBi machinery that could serve as prognostic markers or predictors of response to therapies targeting this pathway.
- Investigating Mechanisms of Drug Resistance
Explore how alterations in RiBi may contribute to acquired resistance to existing cancer therapies. Understanding these adaptive mechanisms can reveal new strategies to overcome resistance or develop effective combination treatments.
What Can We Do?
Creative Biolabs provides dedicated research services to elucidate the role of RiBi in your specific cancer model, offering clear pathways to identify novel therapeutic targets and understand mechanisms of action. We translate complex biological processes into actionable insights for your drug discovery pipeline. Our focus is on delivering robust data packages that support informed decision-making for your oncology programs.
Core advantages
- Specialized Expertise
Our scientific team possesses deep knowledge and extensive experience specifically in the complex field of RiBi and its deregulation in cancer. We stay at the forefront of scientific advancements, integrating cutting-edge findings into our service offerings.
- Advanced Technology Platforms
We utilize state-of-the-art molecular and cellular biology tools, such as high-resolution microscopy for nucleolar component analysis, and robust in vitro systems to ensure high-quality, reproducible data.
- Customized Research Solutions
At our organization, we recognize the inherent uniqueness of every cancer research endeavor. Creative Biolabs collaborates closely with you to design tailored experimental plans that precisely address your specific hypotheses and research objectives.
- Focus on Translational Impact
Our services are designed not just to generate data, but to provide actionable insights that can accelerate your journey from basic discovery to preclinical development. We focus on identifying novel therapeutic avenues and validating potential drug candidates with a clear path toward clinical relevance, inspired by successes like the development of orally available platinum complexes targeting this pathway.
- Commitment to Quality and Timeliness
We are dedicated to delivering meticulous, high-quality results within agreed-upon timelines, fostering a transparent and collaborative relationship throughout the project lifecycle.
FAQs
Q: How does studying RiBi offer an advantage over targeting other cancer pathways?
A: Cancer cells frequently exhibit an exceptional dependence on elevated rates of protein synthesis to fuel their rapid growth and proliferation, rendering RiBi a critical bottleneck in their progression. Targeting this pathway can thus offer broad anti-cancer activity and potentially address tumors that are resistant to therapies aimed at other pathways. Creative Biolabs can help you explore the specific dependencies in your cancer model of interest – why not schedule a brief chat with our experts to discuss this further?
Q: What types of cancer are most likely to be sensitive to therapies targeting RiBi?
A: Many aggressive cancers demonstrating high proliferation rates often show a strong dependency on upregulated RiBi. Published data and ongoing research suggest significant promise in hematological malignancies, as well as various solid tumors including prostate, breast, liver, and bladder cancers.
Q: Our laboratory has identified a novel compound. Can Creative Biolabs help ascertain its impact on RiBi?
A: Absolutely! This is a core area of our expertise. We can design and execute comprehensive studies to determine if and how your compound affects various stages of ribosome production, from pre-rRNA synthesis and processing to nucleolar integrity and downstream effects on global protein synthesis and cancer cell viability.
Ready to advance your cancer research by exploring the frontier of RiBi? Our expert scientific team is available to discuss your specific project needs.
Reference
- Awad, Dominik, et al. "Inhibiting eukaryotic ribosome biogenesis." BMC biology 17 (2019): 1-16. Distributed under Open Access license CC BY 4.0, without modification.
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