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Tumor Genetics Influence Efficacy of Protein-Degrading Cancer Therapies

Tumor Genetics Influence Efficacy of Protein-Degrading Cancer Therapies

Researchers at the University of Edinburgh have found that the genetic mechanism driving oncogene activation can significantly impact how effectively tumors respond to protein-degrading therapies, known as PROTACs (proteolysis-targeting chimeras). The study, published in Cell Chemical Biology, used β-catenin as a model oncogenic protein. They discovered that tumors where oncogenes are activated by mutations that increase protein stability are more susceptible to degradation. However, if high protein levels are due to increased protein production (e.g., through gene amplification), the PROTACs may be less effective because cells continuously replace the degraded protein. This suggests that a detailed understanding of tumor genetics and how protein targets become activated in cancer is crucial for predicting the activity of protein degraders. The findings highlight that simply measuring the percentage of protein degradation (Dmax) might not tell the whole story, as the absolute amount of residual oncogenic p...

QIMR Berghofer-Led Team Uncovers Cancer Targets in 'Junk DNA' with New Tool

QIMR Berghofer-Led Team Uncovers Cancer Targets in 'Junk DNA' with New Tool

A team led by QIMR Berghofer has developed a new tool to explore the previously dismissed 'junk DNA' region of the human genome, identifying thousands of molecules that could lead to new precision cancer treatments. This breakthrough significantly advances RNA-based medicine by enabling the detection of long non-coding RNA (lncRNA) molecules and determining their roles in cancer growth. For decades, scientific focus was primarily on the 1-2% of the genome that codes for proteins, with the remaining 98% considered non-functional. However, technological advancements are now revealing the crucial importance of this vast region. LncRNA molecules are believed to be 'master' regulators, performing complex functions such as switching genes on or off and controlling cellular processes. These molecules have remained largely unexplored due to their specific expression in certain cell types or diseases and their presence in very small quantities, making them difficult to detect. The new tool allows for mapping the ge...

Boehringer Ingelheim Adopts Owkin's AI Platform K Pro for Drug Discovery in Oncology and Immunology

Boehringer Ingelheim Adopts Owkin's AI Platform K Pro for Drug Discovery in Oncology and Immunology

Boehringer Ingelheim Adopts Owkin's AI Platform K Pro for Drug Discovery in Oncology and Immunology

Precision Oncology Integrates Genomics and Multi-faceted Patient Care for Tailored Cancer Treatment

Precision Oncology Integrates Genomics and Multi-faceted Patient Care for Tailored Cancer Treatment

Precision oncology is evolving beyond simple mutation-to-drug matching by integrating genomics with various aspects of patient care. This approach utilizes serial molecular profiling and liquid biopsies to monitor tumor evolution, allowing for dynamic adjustments in treatment strategies. It combines genomic insights with considerations for metabolism, nutrition, immune-directed strategies, natural medicines, repurposed pharmaceuticals, and conventional oncology. The goal is to understand how a tumor grows, metabolizes, resists treatment, and evades immune surveillance, and then to target these vulnerabilities. Next-generation sequencing (NGS) plays a crucial role by providing a detailed molecular map of an individual patient's cancer, moving away from treating cancers solely based on their tissue of origin. This comprehensive strategy aims to create a more personalized and effective cancer treatment plan.

QIMR Berghofer-Led Team Develops Tool to Identify Cancer Targets in 'Junk DNA'

QIMR Berghofer-Led Team Develops Tool to Identify Cancer Targets in 'Junk DNA'

A research team led by QIMR Berghofer has developed a new tool to explore and understand the previously dismissed 'junk DNA' within the human genome. This breakthrough has led to the discovery of thousands of molecules, specifically long non-coding RNA (lncRNA), that could be crucial for developing new precision cancer treatments. For decades, scientific focus was primarily on the 1-2% of the genome responsible for protein creation, while the remaining 98% was considered non-functional. However, advancements in technology are now revealing the significant role of this vast region. LncRNA molecules are believed to act as 'master' regulators, influencing gene expression and cellular processes. Their elusive nature, being expressed in small quantities in specific cell types or diseases, has made them challenging to study but also ideal candidates for targeted therapies that could selectively eliminate cancer cells without harming healthy ones. Dr. Prakrithi Pavithra, a QIMR Berghofer researcher, emphasized th...

Advanced Imaging Technique Reveals Immune Cell Metabolic States in Blood Samples

Advanced Imaging Technique Reveals Immune Cell Metabolic States in Blood Samples

Scientists at the Morgridge Institute for Research have developed an advanced imaging technique, Optical Metabolic Imaging (OMI), capable of characterizing the metabolic activity within individual immune cells from peripheral blood mononuclear cells (PBMCs). This method, detailed in Biophotonics Discovery, offers a non-destructive way to assess immune cell function, providing more detailed information than traditional cell counts. PBMCs, which are predominantly immune cells, are crucial for understanding disease progression and treatment effects in conditions like certain cancers and immune disorders. The OMI technique utilizes two long-wavelength photons to excite the inherent fluorescence of cell metabolism products, allowing researchers to identify whether PBMCs are metabolically active or quiescent without damaging the cells or requiring chemical labels. This approach achieved 93% accuracy in identifying metabolic states two hours after cell stimulation and could specifically identify quiescent and act...

Scientists Engineer Tobacco and Lettuce to Produce Meat Protein for Enhanced Fake Meat

Scientists Engineer Tobacco and Lettuce to Produce Meat Protein for Enhanced Fake Meat

Scientists Engineer Tobacco and Lettuce to Produce Meat Protein for Enhanced Fake Meat

Fred Hutch Cancer Center Leads $15 Million National Clinical Trial for Older Adults with Acute Myeloid Leukemia

Fred Hutch Cancer Center Leads $15 Million National Clinical Trial for Older Adults with Acute Myeloid Leukemia

Fred Hutch Cancer Center is spearheading a new national clinical trial initiative, backed by a $15 million grant from the Patient-Centered Outcomes Research Institute (PCORI). This initiative aims to identify the most effective treatment strategies for older adults diagnosed with acute myeloid leukemia (AML), an aggressive and rapidly progressing blood cancer. The clinical trial program, led by Dr. Mohamed Sorror, will involve an 18-center U.S. consortium. It will compare stem cell transplantation with non-transplant therapies for AML patients after they achieve remission. This research is crucial given the challenges in treating AML in older populations. Additionally, Fred Hutch researchers, including Dr. Andrew C. Hsieh and Dr. Rashmi Mishra, have identified a molecular switch that allows prostate cancer to evade therapy, opening new avenues for treatment. Separately, Dr. David MacPherson and Dr. Gavin Ha received a $1.5 million grant to develop SCLCpheno-seq, a liquid biopsy for small cell lung cancer (...

Lawmakers and Oncologists Express Concern Over Proposed NIH Budget Cuts for Fiscal Year 2027

Lawmakers and Oncologists Express Concern Over Proposed NIH Budget Cuts for Fiscal Year 2027

Oncologists and lawmakers are raising alarms over potential budget cuts to the National Institutes of Health (NIH), the primary federal agency responsible for medical and public health research. The White House has proposed a fiscal year 2027 budget of $41.4 billion for the NIH, which represents a 12% reduction from the previous year's funding. Dr. Christian Thomas, medical director of clinical research at New England Cancer Specialists, emphasized that current funding directly leads to future treatments and provides a significant return on investment through job creation and economic activity. Julia MacDonald, Maine director of government relations at ACS CAN, highlighted the historical bipartisan support for cancer research funding and urged Congress to provide the highest possible funding for the NIH. Senator Susan Collins, who chairs the Appropriations Committee, has publicly called the proposed cuts to biomedical research funding "inexplicable." Congress has until September 30 to finalize federal fund...

Pharmacogenomics Knowledgebase Renamed ClinPGx, Consolidating Genetic Drug Response Information

Pharmacogenomics Knowledgebase Renamed ClinPGx, Consolidating Genetic Drug Response Information

The Pharmacogenomics Knowledgebase (PharmGKB), an NIH-funded resource hosted at Stanford University, has been renamed ClinPGx. This change is more than just a new name; it represents a consolidation of resources under a single platform at clinpgx.org. ClinPGx now integrates PharmGKB's curated knowledgebase with the Clinical Pharmacogenetics Implementation Consortium (CPIC) dosing guidelines and PharmCAT's genotype-to-phenotype annotation tool. The primary goal of pharmacogenomics is to study how an individual's genes influence their response to drugs, aiming to prevent adverse drug reactions and optimize therapeutic outcomes. ClinPGx provides clinical annotations, dosing guidelines, drug-label pharmacogenomic annotations, pathway diagrams illustrating drug absorption and metabolism, and gene-centric summaries for key pharmacogenes. The resource's curation team reviews evidence to link specific genetic variants to drug response, assigning levels of evidence to each clinical annotation. This integration seek...

N-Power Medicine Secures $32M Series B Funding to Expand Community Oncology Research

N-Power Medicine Secures $32M Series B Funding to Expand Community Oncology Research

N-Power Medicine Secures $32M Series B Funding to Expand Community Oncology Research

Neighborhood Deprivation Linked to Breast Cancer Tumor Genomics and Treatment Disparities

Neighborhood Deprivation Linked to Breast Cancer Tumor Genomics and Treatment Disparities

A multi-institution study in the U.S. has revealed significant associations between neighborhood deprivation and breast cancer tumor genomics, targeted treatment use, and survival outcomes. The research found that patients with metastatic breast cancer (MBC) living in highly deprived neighborhoods exhibited a higher rate of somatic TP53 mutations and lower rates of AKT1 mutations in their circulating tumor DNA (ctDNA) compared to those in less deprived areas. Critically, patients from higher deprivation areas were less likely to receive targeted therapies like PI3K inhibitors, even when eligible due to activating mutations. The study also highlighted significantly shorter overall survival for patients from highly deprived neighborhoods, particularly for Black patients, suggesting an interaction between race and neighborhood deprivation in MBC outcomes.