NCI Center for Cancer Research’s Post

Hello, this is Dr. James Doroshow, DCTD Director. I wanted to let the scientific community know about how NCI’s research resources can uniquely enable cancer researchers to make crucial scientific advances. Here’s one collaborative example that was brought forth with help from researchers across institutions and divisions, including from within NCI Center for Cancer Research.   A first-in-class lactate dehydrogenase inhibitor developed through the NCI Experimental Therapeutics (NExT) Program/Chemical Biology Consortium showed cancer cell death and reduced tumor growth in a Hurthle cell carcinoma (HTC) PDX model that was sourced from the National Cancer Institute (NCI) Patient-Derived Models Repository (PDMR).   This work highlights the value of NCI’s research resources to advancements in this area of research, especially in a rare cancer: understanding the effectiveness of targeting glycolysis in tumor harboring mitochondria electron transfer complex mutations.   Learn more about the PDMR - https://pdmr.cancer.gov/ and the NExT Program - https://next.cancer.gov/ - and see a full list of DCTD research resources - https://lnkd.in/dkCpBTn7   Reference: https://lnkd.in/d48DuA-s

CONDICOS update: First in class Trimerbody aimed to stimulate of type 1 dendritic cells cross-presentation for the treatment of cancer. March 28, 2024 On March 27, 2024, CONDICOS brought together the groups of Luis Alvarez-Vallina (CNIO - Spanish National Cancer Research Centre Cancer Immunotherapy Clinical Research Unit), Ignacio Melero (University of Navarra) and David Sancho Madrid (CNIC - Spanish National Center for Cardiovascular Research / Centro Nac. Investigaciones Cardiovasc.) along with their research teams coordinated by Leadartis led by Marta Compte Grau, MD, PhD and Juan Jose Perez Villar. The consortium discussed the progress in dendritic cell biology for boosting cancer immunogenicity through 4-1BB agonist strategies. The first generation of 4-1BB agonistic antibodies (canonical IgGs) failed due to lack of efficacy or toxicity and a second generation based on Fc silenced IgGs has proven unsuccessful. CONDICOS is funded by the Ministerio de Ciencia e Innovación Agencia Estatal de Investigación -private collaboration projects effort of the State Plan for Scientific, Technical and Innovation Research 2021-2023 and the Plan of Recovery, Transformation and Resilience.

In 2016, ATCC joined the Human Cancer Models Initiative (HCMI): a large collaborative effort to drive innovation and advance the field of cancer research. This international consortium, which includes the National Cancer Institute (NCI), Cancer Research UK (CRUK), Hubrecht Organoid Technology (HUB), and Wellcome Sanger Institute (WSI), had an ambitious plan to create new, advanced patient-derived tumor cell culture models—termed “next-generation cancer models” (NGCMs)—that better represented human cancers than existing cancer cell lines. Furthermore, the models developed by the HCMI would be annotated with clinical, genomic, and molecular data, providing a truly unique resource. The hope was that this collection would facilitate unprecedented opportunities for understanding the complex interactions between genetic, epigenetic, and clinical factors in human cancer. Read more here --> https://lnkd.in/emgwzcps

Disruptive innovation in oncology will come from Space: Did you know that the size of tumors grown in micro-gravity is about 10-fold larger than on ground and of higher tissue fidelity: thus, growth of patient derived tumor cultures in space for selection of most effective chemotherapy drugs as personalized treatment is very promising. Did you know that genes and proteins involved in the regulation of cancer cell proliferation and metastasis, differentially expressed under space flight conditions could pave the way for the development of more effective cancer therapies while offering a valuable new frontier for cancer research. Did you know that cancer cells form 3D spheroids in micro-gravity with larger dimensions compared to cell spheroids culturing using other methods. In addition micro-gravity causes cells to naturally form multicellular spheroids with hypoxia core like real cancer tumors, enabling testing the effect of anticancer drugs against this core. All this and more will be learned and discussed at Health from Space 2024 next March in Cannes. https://lnkd.in/e577GH88 Image credit: Axion Biosystems

Researchers propose a novel #CRISPRCas9 approach that targets passenger single nucleotide variants (SNVs) in genes essential for cancer cell survival, expanding options for cancer therapeutics.   Traditional CRISPR targeting of oncogenic hotspot mutations is limited by their low prevalence in tumours. To broaden available targets, passenger mutations, which do not directly contribute to cancer progression but arise due to genetic instability in cancer cells, are targeted. CRISPR/Cas9 is utilised to cleave essential or haploinsufficient genes in passenger SNV regions, selectively eliminating cancer cells without affecting normal cells.    Approximately 44.8% of solid cancer patients are potentially eligible for this approach, a significant increase compared to the 14.4% with CRISPR/Cas9-applicable oncogenic hotspot mutations. This shows promise in expanding the spectrum of target mutations and increasing the eligible patient population for CRISPR #cancer therapy.   Read the full paper in Nature Portfolio: https://shorturl.at/iCGP3 

Namarta Tolani Wadhwani will defend her Master's thesis, "Identification of Long Non-coding RNAs Associated with Prostate Cancer Aggressiveness," on June 14th at 10 am at Health - Aarhus University.   The project explored the involvement of specific long noncoding RNAs (lncRNAs) in prostate cancer (PCa) and their effects on tumor cell growth. Using CRISPR-based screens and RNA-seq data from PCa patient cohorts, she identified candidate lncRNAs and investigated their correlation with clinicopathological parameters. Functional experiments revealed that overactivation of certain lncRNAs increased cell proliferation, suggesting oncogenic potential, while others were associated with suppressed growth. These findings highlight the potential of lncRNAs as prognostic biomarkers for PCa aggressiveness, paving the way for future clinical applications to improve risk stratification of indolent and aggressive PCa. The main supervisor was professor Karina Dalsgaard Sørensen who is heading the prostate cancer group at MOMA: https://lnkd.in/dVa9ZmE2

Join us at the American Association for Cancer Research (AACR) Annual Meeting 2024 in San Diego where we are presenting new data on the role of immuno-transcriptomic profiling of blood and tumor tissue in identifying gene signatures associated with immunotherapy response in metastatic bladder cancer. Previously we have presented biomarker discovery for prediction of immunotherapy response in bladder cancer patient cohorts. Key results from the current study extend immune-transcriptomic predictive capabilities to pre-clinical models and demonstrate concordance between core biological pathways measured in blood and in the tumor: - Discovery of biomarkers of response to immunotherapy in blood and tumor using a genetically engineered mouse model recapitulating metastatic bladder cancer. - Blood-based biomarkers have emerged as a potent tool to predict responses to immunotherapy - The data highlight systemic orchestration of the immune response upon treatment by sharing core biological pathways related to T-cell activation and proliferation across blood and the tumor. If you're here, do reach out to our Chief Medical & Scientific Officer, Dr. Pedro Romero and let’s meet! #rna #AI #PrecisionOncology #BladderCancer #Immunotherapy

Novel ‘kill-switch’ nanorobot selectively kills cancer cells Researchers at the Karolinska Institutet (Stockholm, Sweden) have recently developed a nanorobot system capable of killing cancer cells in mice. This system works by activating at lower pH, such as within the tumor microenvironment. It is hoped that this could serve as a proof-of-concept for similar stimulus-responsive nanorobotic approaches and introduce a new range of effective cancer therapeutics. The ability of this system to selectively kill cells at lower pH was confirmed using in vitro cytotoxicity experiments on cultured human cells. Following this, the system was administered intravenously to a mouse model with a tumor derived from human breast cancer cells. The administered nanorobot system was found to selectively target cancer cells and reduced tumor growth significantly, with a tumor suppression efficacy of around 70%. #nanorobots #cancer #reseaech #robotics #pharmaceuticals Source - Biotechniques

As part of Cancer Immunotherapy Month, we are proud to share our latest publication in Frontiers in Immunology: "Myeloid and Dendritic Cells Enhance Therapeutics-Induced Cytokine Release Syndrome Features in Humanized BRGSF-HIS Preclinical Model." With our collaborators, we investigated the critical role of myeloid and dendritic cells in therapeutics-induced cytokine release syndrome (CRS). This study demonstrated the enhanced features of CRS in humanized BRGSF-HIS preclinical models, providing valuable insights for predicting and managing potential side effects of cancer immunotherapies. Read the full publication here ➡️ https://hubs.la/Q02BJZ790 #OncologyResearch #DrugDevelopment #Immune2Cancer Frontiers, Cancer Research Institute (CRI)

🔬Researchers at The Institute of Cancer Research, London, are shedding light on why PARP inhibitors stop working in some women with metastatic breast cancer.  🎯 PARP inhibitors selectively target cancer cells with mutations, leaving healthy cells unharmed. 🛑 But cancer cells can develop resistance to PARP inhibitors. The team, led by Professors Andrew Tutt and Chris Lord, identified key mechanisms behind this resistance, including "reversion" mutations in the BRCA genes. 🔍 By analyzing tumor DNA, the researchers pinpointed genetic changes driving resistance. This not only helps predict which patients might develop resistance but also paves the way for designing better treatments to overcome it. 🔬 The study also identified changes in other genes linked to PARP inhibitor resistance, offering valuable insights for future clinical trials. Understanding these genetic variations could lead to tailored treatments for individual patients. 🌟 Professors Tutt and Lord envision a future where tailored treatments based on genetic insights holds promise for detecting resistance early and intervening effectively. Continuing research could develop tests for predicting resistance and innovative treatments to combat it. Bringing  us closer to personalized, effective treatments for metastatic breast cancer.  #BreastCancerResearch #PARPInhibitors #CancerTreatment