tbuckley/cabot-search huggingface dataset:
CLO24-088: Efficacy of Fruquintinib in Less Heavily Pretreated Patients (Pts) With Metastatic Colorectal Cancer (mCRC): Profile-Matched Data From FRESCO and FRESCO-2
Authors: Arvind Dasari, Cathy Eng, Sara Lonardi, Rocio Garcia-Carbonero, Toshiki Masuishi, Chiara Cremolini, Francois Ghiringhelli, Joleen Hubbard, Tanios Bekaii-Saab, Jeremy Jones, Rui-Hua Xu, Lin Shen, Jianming Xu, Yuxian Bai, Yanhong Deng, Ying Yuan, Wei Wei, Jianchang Lin, Lucy Chen, Zhao Yang, William R. Schelman, Shukui Qin, Jin Li
Journal: Journal of the National Comprehensive Cancer Network (2024)

"CLO24-088: Efficacy of Fruquintinib in Less Heavily Pretreated Patients (Pts) With Metastatic Colorectal Cancer (mCRC): Profile-Matched Data From FRESCO and FRESCO-2" published on 05 Apr 2024 by National Comprehensive Cancer Network.
CLO24-069: Pneumonitis Incidences in Metastatic Non–Small Cell Lung Cancer on Immunotherapy: A Systematic Review and Meta-Analysis
Authors: Sakditad Saowapa, Natchaya Polpichai, Pharit Siladech, Chalothorn Wannaphut, Manasawee Tanariyakul, Phuuwadith Wattanachayakul, Pakin Lalitnithi
Journal: Journal of the National Comprehensive Cancer Network (2024)
BPI24-019: Estimation of Impact of Care Gap on Patient Outcome and Health Care Cost Burden Using Real World Data in Early-Stage NSCLC—An Empirical Study for Delay in Surgery
Authors: Atharv Sharma, Manu Prasad, Tianyuan Hu, Arunav Saikia, Prabhakar Gaur, Venkata Sai Sumanth Pulluri, Stuti Jha
Journal: Journal of the National Comprehensive Cancer Network (2024)

"BPI24-019: Estimation of Impact of Care Gap on Patient Outcome and Health Care Cost Burden Using Real World Data in Early-Stage NSCLC—An Empirical Study for Delay in Surgery" published on 05 Apr 2024 by National Comprehensive Cancer Network.
YIA24-001: Spatial Evolution of Immune Cell Dysfunction During Development of Oligometastatic Renal Cell Carcinoma: Secondary Analysis of a Prospective Trial
Authors: Chad Tang, Kieko Hara, Alexander D. Sherry, Alejandra G. Serrano, Larisa V. Kostousov, Sharia D. Hernandez, Wei Lu, Li Shen, Amishi Y. Shah, Eric Jonasch, Jose A. Karam, Surena F. Matin, Nizar Tannir, Jing Wang, Pavlos Msaouel, Kanishka Sircar, Luisa Solis
Journal: Journal of the National Comprehensive Cancer Network (2024)

"YIA24-001: Spatial Evolution of Immune Cell Dysfunction During Development of Oligometastatic Renal Cell Carcinoma: Secondary Analysis of a Prospective Trial" published on 05 Apr 2024 by National Comprehensive Cancer Network.
HSR24-140: A Mindfulness-Based Intervention for Caregivers of Autologous Hematopoietic Stem Cell Transplant Patients: Pilot Study Results
Authors: Min-Jeong Yang, Valerie V. Yepez, Sierra J. Washington, Sarah R. Jones, L. Robert Gore, Sofia Fonseca, Ranjita Poudel, Joseph Pidala, Christine Vinci
Journal: Journal of the National Comprehensive Cancer Network (2024)
HSR24-127: Rectal Cancer Disparities in Age and Overall Survival Among American Indian and Alaska Native Vs Non-Hispanic White Populations
Authors: Broc S. Kelley, Margaret R. Walker, John M. Hampton, Syed Nabeel Zafar, Cibele B. Carroll, Dana Hayden, Andrea Schiefelbein, Bret Benally Thompson, Noelle K. LoConte
Journal: Journal of the National Comprehensive Cancer Network (2024)

"HSR24-127: Rectal Cancer Disparities in Age and Overall Survival Among American Indian and Alaska Native Vs Non-Hispanic White Populations" published on 05 Apr 2024 by National Comprehensive Cancer Network.
CLO24-054: Treatment Outcomes in VEXAS Syndrome in Patients With MDS: A Systematic Review
Authors: Moazzam Shahzad, Muhammad Kashif Amin, Muhammad Fareed Khalid, Ahmad Basharat, Jawad Noor, Sakina Abbas, Iqra Anwar, Mohammad Ammad- Ud-Din, Michael Jaglal
Journal: Journal of the National Comprehensive Cancer Network (2024)
QIM24-189: Molecular Tumor Boards Excellence. Phase 1—State of the Art in Spain
Authors: Rafael López López, Beatriz Belosillo, Miguel Ángel Calleja, Jesús García-Foncillas, Fernando López-Ríos, Laura Mezquita, Luis Paz-Ares, Pedro Pérez Segura, José Luis Rodríguez Peralto, Xavier Solé, Ruth Vera, Ana Vivancos, Paula Gratal, Teresa Pardo, Álvaro Rogado, Carlos Camps
Journal: Journal of the National Comprehensive Cancer Network (2024)
CLO24-073: Contemporary Treatment Patterns for Patients Diagnosed With cT1a Renal Tumors: A National Cancer Database Study
Authors: Dominique Lopez, Aden Swayze, Armin Ghomeshi, Nathan VanderVeer-Harris, Pushan Prabhakar, Arjun Pon Avudaiappan, Ahmed Eldefrawy, Murugesan Manoharan, Jorge Caso
Journal: Journal of the National Comprehensive Cancer Network (2024)
CLO24-063: Red Cell Distribution Width and Putative Severity Markers as Predictors of Short-Term Critical Illness in Hospitalized Cancer Patients
Authors: Gustavo Garcia, Maha Hameed, Kevin Cai Zhen, Manuel Rosario, Karen Hamad, Wilhelmine Wiese-Rometsch, Robert Smith
Journal: Journal of the National Comprehensive Cancer Network (2024)

"CLO24-063: Red Cell Distribution Width and Putative Severity Markers as Predictors of Short-Term Critical Illness in Hospitalized Cancer Patients" published on 05 Apr 2024 by National Comprehensive Cancer Network.
CLO24-071: A Propensity Matched Survival Analysis Comparing Partial Versus Radical Nephrectomy in Patients with Metastatic Renal Cell Carcinoma: A National Cancer Database Study
Authors: Nathan VanderVeer-Harris, Aden Swayze, Ronscardy Mondesir, Raghuram Reddy, Pushan Prabhakar, Arjun Pon Avudaiappan, Ahmed Eldefrawy, Murugesan Manoharan, Jorge Caso
Journal: Journal of the National Comprehensive Cancer Network (2024)

"CLO24-071: A Propensity Matched Survival Analysis Comparing Partial Versus Radical Nephrectomy in Patients with Metastatic Renal Cell Carcinoma: A National Cancer Database Study" published on 05 Apr 2024 by National Comprehensive Cancer Network.
CLO24-070: Partial Versus Radical Nephrectomy: An Age-Wise Comparison of the National Cancer Database
Authors: Dianelis Gonzalez Pupo, Daniel Boaretto, Armin Ghomeshi, Dominique Lopez, Pushan Prabhakar, Arjun Pon Avudaiappan, Ahmed Eldefrawy, Murugesan Manoharan, Jorge Caso
Journal: Journal of the National Comprehensive Cancer Network (2024)
CLO24-078: Hippocampal Optimization and Dosimetric Analysis on Feasibility of Hippocampal Sparing in Primary Gliomas—A Retrospective Dosimetric Study in a Tertiary Care Center
Authors: R Arjuhn, S Jeeva, TN Vijayasree
Journal: Journal of the National Comprehensive Cancer Network (2024)

"CLO24-078: Hippocampal Optimization and Dosimetric Analysis on Feasibility of Hippocampal Sparing in Primary Gliomas—A Retrospective Dosimetric Study in a Tertiary Care Center" published on 05 Apr 2024 by National Comprehensive Cancer Network.
EPR24-113: The Role of Social Determinants of Health in Gastrointestinal Cancer Outcomes in the United States Context: A Systematic Review
Authors: Brenda Santellano, Rashi Agrawal, Gabriela Duchesne, Muhannad Sharara, E. Andrew Balas, Gagan Agrawal, Meng-Han Tsai, Asha Nayak-Kapoor, Jorge E. Cortes
Journal: Journal of the National Comprehensive Cancer Network (2024)

"EPR24-113: The Role of Social Determinants of Health in Gastrointestinal Cancer Outcomes in the United States Context: A Systematic Review" published on 05 Apr 2024 by National Comprehensive Cancer Network.
CLO24-058: Evaluation of Aromatherapy With Lavender Oil During the Perioperative Period of Benign Prostate Hyperplasia: A Randomized Placebo Controlled Clinical Observation
Authors: Jiping Chen, Lijun Tang
Journal: Journal of the National Comprehensive Cancer Network (2024)

"CLO24-058: Evaluation of Aromatherapy With Lavender Oil During the Perioperative Period of Benign Prostate Hyperplasia: A Randomized Placebo Controlled Clinical Observation" published on 05 Apr 2024 by National Comprehensive Cancer Network.
Functional CRISPR screens in T cells reveal new opportunities for cancer immunotherapies
Authors: Minghua Xiang, Huayi Li, Yuanyuan Zhan, Ding Ma, Qinglei Gao, Yong Fang
Journal: Molecular Cancer (2024)

Abstract T cells are fundamental components in tumour immunity and cancer immunotherapies, which have made immense strides and revolutionized cancer treatment paradigm. However, recent studies delineate the predicament of T cell dysregulation in tumour microenvironment and the compromised efficacy of cancer immunotherapies. CRISPR screens enable unbiased interrogation of gene function in T cells and have revealed functional determinators, genetic regulatory networks, and intercellular interactions in T cell life cycle, thereby providing opportunities to revamp cancer immunotherapies. In this review, we briefly described the central roles of T cells in successful cancer immunotherapies, comprehensively summarised the studies of CRISPR screens in T cells, elaborated resultant master genes that control T cell activation, proliferation, fate determination, effector function, and exhaustion, and highlighted genes ( BATF , PRDM1 , and TOX ) and signalling cascades (JAK-STAT and NF-κB pathways) that extensively engage in multiple branches of T cell responses. In conclusion, this review bridged the gap between discovering element genes to a specific process of T cell activities and apprehending these genes in the global T cell life cycle, deepened the understanding of T cell biology in tumour immunity, and outlined CRISPR screens resources that might facilitate the development and implementation of cancer immunotherapies in the clinic.
DNA double-stranded breaks, a hallmark of aging, defined at the nucleotide resolution, are increased and associated with transcription in the cardiac myocytes in LMNA-cardiomyopathy
Authors: Benjamin Cathcart, Sirisha M Cheedipudi, Leila Rouhi, Zhongming Zhao, Priyatansh Gurha, Ali J Marian
Journal: Cardiovascular Research (2024)

Abstract Aims An intrinsic feature of gene transcription is the formation of DNA superhelices near the transcription bubble, which are resolved upon induction of transient double-stranded breaks (DSBs) by topoisomerases. Unrepaired DSBs are pathogenic as they lead to cell cycle arrest, senescence, inflammation, and organ dysfunction. We posit that DSBs would be more prevalent at the genomic sites that are associated with gene expression. The objectives were to identify and characterize genome-wide DSBs at the nucleotide resolution and determine the association of DSBs with transcription in cardiac myocytes. Methods and results We identified the genome-wide DSBs in ∼1 million cardiac myocytes per heart in three wild-type and three myocyte-specific LMNA-deficient (Myh6-Cre:LmnaF/F) mice by END-Sequencing. The prevalence of DSBs was 0.8% and 2.2% in the wild-type and Myh6-Cre:LmnaF/F myocytes, respectively. The END-Seq signals were enriched for 8 and 6764 DSBs in the wild-type and Myh6-Cre:LmnaF/F myocytes, respectively (q &amp;lt; 0.05). The DSBs were preferentially localized to the gene regions, transcription initiation sites, cardiac transcription factor motifs, and the G quadruplex forming structures. Because LMNA regulates transcription through the lamin-associated domains (LADs), we defined the LADs in cardiac myocytes by a Cleavage Under Targets &amp; Release Using Nuclease (CUT&amp;RUN) assay (N = 5). On average there were 818 LADs per myocyte. Constitutive LADs (cLADs), defined as LADs that were shared by at least three genomes (N = 2572), comprised about a third of the mouse cardiac myocyte genomes. Transcript levels of the protein-coding genes located at the cLADs (N = 3975) were ∼16-fold lower than those at the non-LAD regions (N = ∼17 778). The prevalence of DSBs was higher in the non-LAD as compared to the cLAD regions. Likewise, DSBs were more common in the loss-of-LAD regions, defined as the genomic regions in the Myh6-Cre:LmnaF/F that were juxtaposed to the LAD regions in the wild-type myocytes. Conclusion To our knowledge, this is the first identification of the DSBs, at the nucleotide resolution in the cardiovascular system. The prevalence of DSBs was higher in the genomic regions associated with transcription. Because transcription is pervasive, DSBs are expected to be common and pathogenic in various states and aging.
Cancer immunometabolism: advent, challenges, and perspective
Authors: Qin Dang, Borui Li, Bing Jin, Zeng Ye, Xin Lou, Ting Wang, Yan Wang, Xuan Pan, Qiangsheng Hu, Zheng Li, Shunrong Ji, Chenjie Zhou, Xianjun Yu, Yi Qin, Xiaowu Xu
Journal: Molecular Cancer (2024)

Abstract For decades, great strides have been made in the field of immunometabolism. A plethora of evidence ranging from basic mechanisms to clinical transformation has gradually embarked on immunometabolism to the center stage of innate and adaptive immunomodulation. Given this, we focus on changes in immunometabolism, a converging series of biochemical events that alters immune cell function, propose the immune roles played by diversified metabolic derivatives and enzymes, emphasize the key metabolism-related checkpoints in distinct immune cell types, and discuss the ongoing and upcoming realities of clinical treatment. It is expected that future research will reduce the current limitations of immunotherapy and provide a positive hand in immune responses to exert a broader therapeutic role.
Abstract LB106: Ultra-short ctDNA: A new paradigm for ctDNA liquid biopsy
Authors: Feng Li, Fang Wei, Hua-Jun He, Chien-Chung Lin, Szu-Chun Yang, Allen Wei-Lun Huang, Cheuk Ying Tang, Yong Kim, David T. Wong
Journal: Cancer Research (2024)

Abstract Mononucleosomal ctDNA (mnctDNA, 157-bp, double-stranded) spearheads liquid biopsy (LB) for cancer detection, treatment and clinical care. The bottleneck of mnctDNA LB are low copy number of ctDNA and limit of detection of platform technologies. Recent discovery of ultra-short ctDNA (usctDNA, 52-54 nt, single-stranded) that harbors somatic mutations prompted us to explore the quantification and stoichiometry of usctDNA to mnctDNA in plasma and saliva of NSCLC patients. Paired plasma and saliva from 20 advanced NSCLC patients with tissue genotyped positive for L858R were processed for cfDNA extraction and quantification with Qubit and Tape Station. Digital PCR assays targeting L858R somatic mutation to generate amplicons of 57-bp (usctDNA) and 100-bp (mnctDNA) were performed by UCLA and independently by NIST. Results in Table 1 revealed that three findings of usctDNA that will have potential to impact ctDNA liquid biopsy. First, the somatic mutation (L858R) is present in usctDNA. Second, The stoichiometric ratio of usctDNA to mnctDNA is similar in plasma and saliva at 1.6X. For the wild-type counterpart, the ratio is 1.1X for plasma and 0.6X for saliva. Third, the copy number of usctDNA and mnctDNA in saliva to plasma is 7.8X and 7.7X. Conclusion: Detection of tumor-associated/specific EGFR L858R somatic mutations in uscfDNA is translationally impactful, adding 1.6X of the ctDNA targets for molecular detection, effectively cumulating 2.6X of total ctDNA targets, permitting earlier cancer detection, treatment monitoring and therapy prognostication. The finding that saliva harbors 7X of the us- and mnctDNA further raises the prospect of advancing saliva ctDNA liquid biopsy for NSCLC detection as it may effectively allow 15.5X (7.8X+7.7X) ability to detect malignancy-associated ctDNA. Table 1. Quantification of usctDNA and mnctDNA in Plasma and Saliva Mut usctDNA (L858R) WT cfDNA usctDNA mnctDNA U/M uscfDNA mncfDNA U/M Plasma 1555 ± 326 964 ± 209 1.6X 15201 ± 1509 13261 ± 1424 Saliva 12158 ± 1731 7442 ± 1020 1.6X 340896 ± 27170 601733 ± 71573 1.1X Saliva/Plasma (fold X) 7.8 7.7 1.6X 22.4 45.3 0.6X Citation Format: Feng Li, Fang Wei, Hua-Jun He, Chien-Chung Lin, Szu-Chun Yang, Allen Wei-Lun Huang, Cheuk Ying Tang, Yong Kim, David T. Wong. Ultra-short ctDNA: A new paradigm for ctDNA liquid biopsy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB106.
Abstract LB453: Distinct mechanism of CXCR7 activation in EGFR-mutated NSCLC by chemokines
Authors: Laura C. Gunder, Ines Pulido, Jeffrey H. Becker, Malek G. Massad, Takeshi Shimamura
Journal: Cancer Research (2024)

Abstract Erlotinib and gefitinib, EGFR TKIs, have markedly improved outcomes for NSCLC patients with EGFR mutations. However, resistance eventually develops, with the T790M mutation evident in over 50% of resistant tumors. Other resistance pathways include MET amplification, SCLC transformation, and EMT. Osimertinib, a third-generation EGFR TKI, targets the T790M mutation and is approved as a first-line treatment, reducing the incidence of T790M-related resistance. Nonetheless, non-T790M resistance mechanisms such as mesenchymal transformation are on the rise. The molecular targets or exact mechanisms of EGFR TKI resistance with mesenchymal phenotypes remain elusive. We have discovered that ERK reactivation, commonly found in EGFR TKI-resistant cells with a mesenchymal phenotype, is due to activation of an atypical GPCR, CXC chemokine receptor type 7 (CXCR7). CXCR7 is overexpressed in a cell line, an EGFR TKI-resistant tumor model, and in samples from patients that progressed on EGFR TKIs. Currently, there are no effective CXCR7 inhibitors to evaluate in NSCLC; the mechanisms and ligands for CXCR7 are not fully understood. To evaluate ligand-dependent activation of CXCR7, we generated HEK293 cells and EGFR-mutant NSCLC cells ectopically-expressing CXCR7 and stimulated the cells with CXCL12, a well-documented ligand for CXCR7. Exposures of HEK293 cells with CXCR7 to CXCL12 resulted in the internalization of CXCR7 followed by the activation of the MAPK pathway within 30 minutes of EGFR TKI treatment whereas MAPK activation in EGFR mutant NSCLC cells took 8 hours. MIF activation was also delayed in NSCLC compared to the HEK293 model, requiring the presence of an EGFR TKI. We discovered that CXCR7 co-immunoprecipitated with mutant EGFR in NSCLC cells while CXCR7 did not co-immunoprecipitate when EGFR was inhibited. Furthermore, we discovered additional chemokines including GDF15 that activate the CXCR7-MAPK axis and promote cell migration, a key characteristic of the mesenchymal phenotype in EGFR mutant cells. Taken together, we elucidated a unique mechanism of ligand-induced activation of CXCR7 and downstream MAPK pathway by canonical and putative ligands. This complex mechanism of CXCR7 activation in EGFR mutant NSCLC suggests that preventing the receptor-ligand binding may not be feasible in the context of overcoming EGFR TKI resistance. Citation Format: Laura C. Gunder, Ines Pulido, Jeffrey H. Becker, Malek G. Massad, Takeshi Shimamura. Distinct mechanism of CXCR7 activation in EGFR-mutated NSCLC by chemokines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB453.
Abstract LB179: Identification of the highly potent and orally available ER-targeting PROTAC degrader HP568 for the treatment of breast cancer
Authors: Wu Du, Zhilin Tu, Dekun Qin, Haibo Li, Jingyi Duan, Shijuan Liu, Meng Zhang, Zhenyan Nie, Zhihui Yuan, Jing Li, Xinghai Li
Journal: Cancer Research (2024)

Abstract Breast cancer remains an unmet medical need. It has become the most occurring and deadliest cancer for women globally. Estrogen receptor (ER) is expressed in 75% of breast cancers and has the key role in tumorigenesis and progression of ER+ breast cancers. Endocrine treatments that target ER are the mainstay therapies for the ER+ breast cancers, yet drug resistance unavoidably develops due to mutations in the ER gene. The ER-targeting proteolysis targeting chimera (PROTAC) degrader is an emerging new modality that interrupts the ER signaling through degradation of ER and offers unprecedented potential for solving the endocrine resistance. We have discovered HP568, an ER-targeting PROTAC that is highly potent against both the wild-type ER and ER mutants. HP568 has a favorable ADME profile that is superior to known competitor ER-targeting PROTAC. In the head-to-head comparison efficacy studies, HP568 has demonstrated the dose-dependent and superior efficacy that is well consistent with the drug exposure profile and PD biomarkers. HP568 also shows a synergetic effect in combination with a CDK4/6 inhibitor. HP568 is clean in the secondary pharmacology profiling, and well tolerated in animal tox studies. HP568 is under the preclinical development and has the potential to be the best-in-class ER-targeting degrader. HP568 structure will not be disclosed. Citation Format: Wu Du, Zhilin Tu, Dekun Qin, Haibo Li, Jingyi Duan, Shijuan Liu, Meng Zhang, Zhenyan Nie, Zhihui Yuan, Jing Li, Xinghai Li. Identification of the highly potent and orally available ER-targeting PROTAC degrader HP568 for the treatment of breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB179.
Abstract ND05: The discovery of ARV-393, a potent, orally bioavailable BCL6 targeting PROTAC® for the treatment of Non-Hodgkin’s Lymphoma
Authors: Dan Sherman
Journal: Cancer Research (2024)

Abstract Discovery of ARV-393, a potent, orally bioavailable BCL6 targeting PROTAC® for the treatment of Non-Hodgkin’s Lymphoma (NHL)Dan Sherman, Sheryl M. Gough, Lynn DeCarr, Sarah Eaton, Mark Bookbinder, Jennifer Pizzano, Elizabeth Bortolon, John Corradi, Rashaun Wilson, Daniel Rogoz, Ram Lingamaneni, Wei Zhang, Michelle Zhang, Xin Chen, Gan Wang, Hanqing Dong, Michael Berlin, Keith R. Hornberger, Lawrence Snyder, Achal Pashine and Ian Taylor. Arvinas, Inc., 5 Science Park, New Haven, CT, USA. Approximately 18,000 cases of Diffuse large B-cell lymphomas (DLBCL) are diagnosed worldwide per year making this cancer the most prevalent (30%) of the non-Hodgkin’s Lymphomas (NHL). Despite the success of R-CHOP treatment, approximately 40% of patients are refractory or relapse. While much progress has been made with CAR-Ts and bi-specific antibodies following frontline therapy in recent years, there remains a need for an orally bioavailable small-molecule that targets molecular drivers of NHL. The BCL6 transcription factor has long been known as an oncogenic driver of B-cell malignancy. The BCL6 gene has been found to be translocated and/or mutated resulting in deregulation of its expression, predominantly in DLBCL and Burkitt’s lymphoma (BL). The deregulated expression and scaffolding role of BCL6 in the transcriptional repressor complex make it an ideal target for the PROteolysis Targeting Chimera (PROTAC®) technology with one BCL6 degrader recently entering Phase 1 trials. We undertook a medicinal chemistry campaign to identify a BCL6-targeting PROTAC®. This effort identified ARV-393, an orally bioavailable PROTAC® that recruits BCL6 and the E3 ligase cereblon to rapidly degrade BCL6 via the cell’s natural ubiquitin proteasome system. ARV-393 is potent, demonstrating DC50 and GI50 values &amp;lt;1 nM in numerous DLBCL and BL cell lines. This agent demonstrates deep BCL6 degradation in vitro and in vivo, resulting in excellent TGI in several tumor xenograft models supporting a first-in-human trial in 1H 2024. We will present the chemical structure of ARV-393 and selected pre-clinical data. Citation Format: Dan Sherman. The discovery of ARV-393, a potent, orally bioavailable BCL6 targeting PROTAC® for the treatment of Non-Hodgkin’s Lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr ND05.