RAD51

NEW YORK, April 3, 2025 /PRNewswire/ -- A study led by NYU Langone Health researchers sheds light on how the major cancer gene BRCA2 determines which cancer cells can be killed by a class of precision cancer drugs called PARP inhibitors. Recently published in Nature, the work builds on the fact that, as human cells divide and grow, DNA damage occurs continuously and must be swiftly repaired to prevent cancer. BRCA2 is a key player in such a mechanism, homology-directed repair, but genetic changes, called mutations, occur and accumulate in cells, with some sabotaging the gene's DNA repair role to create cancer risk. Cancer cells also require DNA repair as their reckless growth causes a quick, lethal build-up of errors unless countered. When mutations hinder BRCA2 function, cancer cells are known to rely on the poly ADP-ribose polymerase 1 (PARP1) pathway for back-up DNA repair, and to continue abnormal growth. PARP inhibitors were designed to stop this. Now the new study, led by scientists at NYU Langone Health, reveals an unexpected role for BRCA2 in controlling the action of PARP1 at DNA damage sites, and explains why PARP inhibitors are effective in some patients but not in others. The effectiveness of PARP inhibitors in any cancer cell, the study authors found, depends on how well BRCA2 works there. While the percentage of cancer cells with functioning BRCA2 is hard to estimate accurately, it matters. As a proxy measure, past studies have shown that 15–20% of ovarian, 6–8% of breast, 8–10% of prostate, and 8–10% of pancreatic cancer cases feature either inherited BCRA2 mutations or those that arise for the first time as cells multiply in tumors. "This work is part of a larger effort across NYU Langone and Perlmutter Cancer Center to connect molecular discovery with clinical advances," said senior study author Eli Rothenberg, Ph.D., professor in the Department of Biochemistry & Molecular Pharmacology at NYU Grossman School of Medicine, and director of Single Molecule Biophotonics. "Through collaborations with clinical teams, we are set to translate insights about BRCA-related pathways into actionable diagnostics and new treatment strategies." Molecular Shield While many cancer patients see a temporary remission with PARP inhibitors, results vary greatly. To understand why, and to clarify the BRCA2-PARP1 interplay, the research team turned to proprietary imaging techniques developed at NYU Langone. "This finding would not have been possible without the specialized imaging tools pioneered by the Single Molecule Biophotonics program here," said Dr. Rothenberg. "They gave us a molecular window into how BRCA2 protects DNA repair complexes from disruption in living human cells in real time, bringing us closer to developing truly individualized cancer therapies." Single-molecule imaging revealed that BRCA2 functions as a molecular shield, physically preventing PARP1 from remaining stuck at DNA repair sites, the mechanism by which PARP inhibitors have their effect. Specifically, the researchers found that intact BRCA2 ensures that RAD51—a protein essential for accurate DNA repair—can access repair sites instead of PARP1, and carry out its function. This prevents the treatment-generated buildup of harmful DNA breaks in cancer cells that resist PARP inhibition. By contrast, in cells with defective BRCA2, PARP1 is free to bind to, and persist at, sites of DNA damage. This blocks RAD51 access and halts proper repair, causing fatal damage to cancer cells—a mechanism that explains the greater vulnerability of BRCA2-deficient tumor cells to PARP inhibitors. "Moving forward, our team is focused on how this mechanism can be used clinically," said first study author Sudipta Lahiri, Ph.D., the postdoctoral fellow at NYU Langone who led the experimental work. "The finding that variable BRCA2 activity dictates PARP inhibitor efficacy points to the need for patient-specific tumor profiling and may inform how clinicians select therapies. We are also looking at the structure of BRCA2 domains involved its ability to shield repair complexes from PARP1 with the goal of designing therapies that overcome resistance." Along with Drs. Rothenberg and Lahiri, study authors from the Department of Biochemistry and Molecular Pharmacology at NYU Grossman School of Medicine included Tony Huang, Ph.D., professor of Biochemistry and Molecular Pharmacology; George Hamilton, Ph.D.; and M.D./Ph.D. student Liana Goehring. From the Department of Therapeutic Radiology at Yale University School of Medicine, co-authors included Gemma Moore and co-senior author Ryan Jensen, Ph.D. The study was supported by National Institutes of Health (and National Cancer Institute) grants GM134947, AI153040, CA247773 and CA288368, CA270788 and CA215990, GM139610, ES031658 and CA288368, as well as by the V Foundation, the Gray Foundation, the Laura Chang and Arnold Chavkin Charitable Donation, the Goldberg Family Foundation, and a Perlmutter Cancer Center support grant. About NYU Langone Health NYU Langone Health is a fully integrated health system that consistently achieves the best patient outcomes through a rigorous focus on quality that has resulted in some of the lowest mortality rates in the nation. Vizient Inc. has ranked NYU Langone No. 1 out of 115 comprehensive academic medical centers across the nation for three years in a row, and U.S. News & World Report recently placed nine of its clinical specialties among the top five in the nation. NYU Langone offers a comprehensive range of medical services with one high standard of care across seven inpatient locations, its Perlmutter Cancer Center, and more than 320 outpatient locations in the New York area and Florida. With $14.2 billion in revenue this year, the system also includes two tuition-free medical schools, in Manhattan and on Long Island, and a vast research enterprise. CONTACT: Gregory Williams, [email protected] SOURCE NYU Langone Health System WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Advances in immunotherapy have ushered in a new era of treatment for follicular lymphoma (FL), particularly for patients who have experienced relapse after conventional chemotherapy regimens. This paradigm shift is characterized by the emergence of innovative therapies like CAR T-cell therapy and bispecific antibodies, which have demonstrated remarkable efficacy in targeting and eradicating lymphoma cells. CAR T-cell therapy represents a groundbreaking approach where a patient's own T-cells are genetically engineered to recognize and attack cancer cells. This personalized treatment has shown significant promise, especially for individuals who have undergone extensive previous therapies. One notable example is Axicabtagene ciloleucel (Yescarta), a CAR T-cell therapy approved for use in patients with relapsed or refractory follicular lymphoma. Clinical trials have highlighted its ability to induce durable remissions, with some patients experiencing long-term remission even after multiple prior therapies. LAS VEGAS, Nov. 28, 2024 /PRNewswire/ -- DelveInsight's ' Follicular Lymphoma Pipeline Insight 2024 ' report provides comprehensive global coverage of pipeline follicular lymphoma therapies in various stages of clinical development, major pharmaceutical companies are working to advance the pipeline space and future growth potential of the follicular lymphoma pipeline domain. Key Takeaways from the Follicular Lymphoma Pipeline Report DelveInsight's follicular lymphoma pipeline report depicts a robust space with 50+ active players working to develop 55+ pipeline therapies for follicular lymphoma treatment. Key follicular lymphoma companies such as Chia Tai Tianqing Pharmaceutical Group, Incyte Corporation, Mabworks, Johnson & Johnson Innovative Medicine, Nektar Therapeutics, Xynomic Pharmaceuticals, Merck Sharp & Dohme, Jiangsu HengRui Medicine Co., Ltd., ADC Therapeutics, Bristol-Myers Squibb, Swedish Orphan Biovitrum, Zhejiang DTRM Biopharma, Immpact Bio, Galapagos, Immunitas Therapeutics, Enterome, CRISPR Therapeutics, CHO Pharma, Shanghai Blueray Biopharma, BeiGene, AstraZeneca, AVM Biotechnology, Mustang Bio, Merck, Pell Bio-Med Technology, Schrodinger Inc., Sana Biotechnology, Poseida Therapeutics, OncoNano Medicine, Inc., Nurix Therapeutics, Inc., NovalGen, Pfizer, Xencor, Wellington Zhaotai Therapies, MEI Pharma, Sutro Biopharma, Synthekine, Verismo Therapeutics, Vincerx Pharma, Novartis, Century Therapeutics, Newave Pharmaceuticals, Bio-Path Holdings, Affimed GmbH, Iksuda Therapeutics, Allogene Therapeutics, Adicet Bio, Carna Biosciences, Inc., BeiGene, Boryung Pharmaceutical, Accutar Biotechnology, Atara Biotherapeutics, AbbVie, InnoCare Pharma, NeoImmuneTech, and others are evaluating new follicular lymphoma drugs to improve the treatment landscape. Promising follicular lymphoma pipeline therapies such as Parsaclisib, TQ-B3525, Tafasitamab, MIL62, Ibrutinib, AZD0486, NKTR-255, Abexinostat, Acalabrutinib, Zilovertamab vedotin, SHR2554, Nivolumab, Loncastuximab tesirine, Golcadomide, Emapalumab, DTRM-555, Capivasertib, IMPT 314, GLPG5101, IMT-009, EO2463, CTX112, CHO-H01, BR1733, BGB-16673, BGB-10188, AZD5492, AVM0703, MB106, MK-1026, PL001, SGR-1505, SC291, SC262, P-CD19CD20-ALLO1, ONM 501, NX-5948, NX 2127, NVG-111, Mevrometostat, Plamotamab, WZTL-002, Voruciclib, STRO001, SYNCAR-001 + STK-009, SynKIR-310, VIP-152, VAY736, CNTY-101, LP-168, BP1002, IOA-244, IKS 03, ALLO-501, ADI-001, AS-1763, BGB-21447, BR101801, AC676, ATA3219, ABBV-319, ABBV-101, ICP-B02, ICP-B05, C-CAR039, Efineptakin Alfa, and others are under different phases of follicular lymphoma clinical trials. In August 2024, the company expects to file a supplemental Biologics License Application for tafasitamab for the treatment of patients with FL who have failed at least one prior systemic anti-CD20 immunotherapy or chemo-immunotherapy by the end of 2024 based on the positive Phase III results. In June 2024, a consortium of Eugene Private Equity and Korea Development Bank Private Equity announced that they would acquire 80% of South Korean vaccine maker Boryung Biopharma Co. for 320 billion won (USD 231 million). In February 2024, Incyte announced that it had entered into an asset purchase agreement with MorphoSys AG, which gives Incyte exclusive global rights for tafasitamab. Incyte will now recognize revenue and cost for all US commercialization and clinical development and MorphoSys will no longer be eligible to receive future milestone, profit split and royalty payments. In September 2023, OncoNano Medicine, Inc. announced a clinical trial supply agreement with Regeneron for the use of Libtayo (cemiplimab), a PD-1 inhibitor, in the combination stage of the first human trial of ONM-501, a dual-activating STING (STimulator of INterferon Genes) agonist and lead therapeutic development candidate. The ONM-501 first-in-human trial is a multicenter Phase Ia/b dose escalation and dose expansion study of intratumoral ONM-501 as monotherapy and in combination with Libtayo in patients with advanced solid tumors and lymphomas. OncoNano is the sponsor of the clinical trial, and Regeneron will supply cemiplimab. In May 2023, Janssen Pharmaceutical Companies of Johnson & Johnson announced that it had entered into a worldwide collaboration and license agreement with Cellular Biomedicine Group Inc. (CBMG) to develop, manufacture, and commercialize next-generation chimeric antigen receptor (CAR) T-cell therapies for the treatment of B-cell malignancies. Under the terms of the agreement, CBMG will grant Janssen a worldwide license to develop and commercialize the CAR-T assets, except in Greater China. Janssen and CBMG will negotiate an option for Janssen to commercialize the products in the Chinese territory. Janssen will make an upfront payment of USD 245 million that will be accounted for in the second quarter as a research and development expense. Additional future payments will be based upon achieving certain development, regulatory, and sales milestones, as well as tiered royalty payments on worldwide net trade sales, excluding Greater China. Request a sample and discover the recent advances in follicular lymphoma treatment drugs @ Follicular Lymphoma Pipeline Report The follicular lymphoma pipeline report provides detailed profiles of pipeline assets, a comparative analysis of clinical and non-clinical stage follicular lymphoma drugs, inactive and dormant assets, a comprehensive assessment of driving and restraining factors, and an assessment of opportunities and risks in the follicular lymphoma clinical trial landscape. Follicular Lymphoma Overview Follicular lymphoma is a common type of non-Hodgkin lymphoma (NHL) that originates from B-cells, a kind of white blood cell responsible for producing antibodies. This cancer is characterized by the growth of abnormal lymphoid follicles, which can disrupt normal lymphatic function. While the exact causes of follicular lymphoma are not fully understood, certain factors may increase the risk, including age (most commonly affecting adults over 60), a family history of lymphoma, and potential environmental factors such as exposure to pesticides or chemicals. Symptoms of follicular lymphoma can vary widely but may include painless swelling of lymph nodes in the neck, armpit, or groin, unexplained weight loss, night sweats, fatigue, and fever. Some patients may remain asymptomatic for extended periods, as this type of lymphoma can progress slowly. Diagnosis typically involves a combination of physical examinations, blood tests, imaging studies (like CT scans), and a biopsy of affected lymph nodes. The biopsy helps determine the subtype and stage of the lymphoma, which is crucial for planning treatment. Treatment for follicular lymphoma depends on the stage of the disease and the patient's overall health. Options may include watchful waiting for asymptomatic cases, chemotherapy, immunotherapy (such as monoclonal antibodies), and targeted therapies. In some cases, stem cell transplants may be considered for patients with more aggressive forms or those who do not respond to initial treatments. Given the indolent nature of follicular lymphoma, ongoing management, and regular monitoring are vital for achieving the best possible outcomes. Find out more about follicular lymphoma treatment drugs @ Drugs for Follicular Lymphoma Treatment A snapshot of the Follicular Lymphoma Pipeline Drugs mentioned in the report: Learn more about the emerging follicular lymphoma pipeline therapies @ Follicular Lymphoma Clinical Trials Follicular Lymphoma Therapeutics Assessment The follicular lymphoma pipeline report proffers an integral view of the follicular lymphoma emerging novel therapies segmented by stage, product type, molecule type, mechanism of action, and route of administration. Scope of the Follicular Lymphoma Pipeline Report Coverage: Global Therapeutic Assessment By Product Type: Mono, Combination, Mono/Combination Therapeutic Assessment By Clinical Stages: Discovery, Pre-clinical, Phase I, Phase II, Phase III Therapeutics Assessment By Route of Administration: Intra-articular, Intraocular, Intrathecal, Intravenous, Oral, Parenteral, Subcutaneous, Topical, Transdermal Therapeutics Assessment By Molecule Type: Oligonucleotide, Peptide, Small molecule Therapeutics Assessment By Mechanism of Action: Phosphatidylinositol 3 kinase delta inhibitors, Phosphatidylinositol 3 kinase gamma inhibitors, Emt protein-tyrosine kinase inhibitors, Interleukin 15 receptor agonists, Histone deacetylase inhibitors, Rad51 recombinase inhibitors, Agammaglobulinaemia tyrosine kinase inhibitors, Apoptosis stimulants, Cell cycle inhibitors, Tubulin inhibitors, Tubulin polymerisation inhibitors, Enhancer of zeste homolog 2 protein inhibitors, Antibody-dependent cell cytotoxicity, Programmed cell death 1 receptor antagonists, T lymphocyte stimulants, Alkylating agents, DNA cross-linking agents Key Follicular Lymphoma Companies: Chia Tai Tianqing Pharmaceutical Group, Incyte Corporation, Mabworks, Johnson & Johnson Innovative Medicine, Nektar Therapeutics, Xynomic Pharmaceuticals, Merck Sharp & Dohme, Jiangsu HengRui Medicine Co., Ltd., ADC Therapeutics, Bristol-Myers Squibb, Swedish Orphan Biovitrum, Zhejiang DTRM Biopharma, Immpact Bio, Galapagos, Immunitas Therapeutics, Enterome, CRISPR Therapeutics, CHO Pharma, Shanghai Blueray Biopharma, BeiGene, AstraZeneca, AVM Biotechnology, Mustang Bio, Merck, Pell Bio-Med Technology, Schrodinger Inc., Sana Biotechnology, Poseida Therapeutics, OncoNano Medicine, Inc., Nurix Therapeutics, Inc., NovalGen, Pfizer, Xencor, Wellington Zhaotai Therapies, MEI Pharma, Sutro Biopharma, Synthekine, Verismo Therapeutics, Vincerx Pharma, Novartis, Century Therapeutics, Newave Pharmaceuticals, Bio-Path Holdings, Affimed GmbH, Iksuda Therapeutics, Allogene Therapeutics, Adicet Bio, Carna Biosciences, Inc., BeiGene, Boryung Pharmaceutical, Accutar Biotechnology, Atara Biotherapeutics, AbbVie, InnoCare Pharma, NeoImmuneTech, and others. Key Follicular Lymphoma Pipeline Therapies: Parsaclisib, TQ-B3525, Tafasitamab, MIL62, Ibrutinib, AZD0486, NKTR-255, Abexinostat, Acalabrutinib, Zilovertamab vedotin, SHR2554, Nivolumab, Loncastuximab tesirine, Golcadomide, Emapalumab, DTRM-555, Capivasertib, IMPT 314, GLPG5101, IMT-009, EO2463, CTX112, CHO-H01, BR1733, BGB-16673, BGB-10188, AZD5492, AVM0703, MB106, MK-1026, PL001, SGR-1505, SC291, SC262, P-CD19CD20-ALLO1, ONM 501, NX-5948, NX 2127, NVG-111, Mevrometostat, Plamotamab, WZTL-002, Voruciclib, STRO001, SYNCAR-001 + STK-009, SynKIR-310, VIP-152, VAY736, CNTY-101, LP-168, BP1002, IOA-244, IKS 03, ALLO-501, ADI-001, AS-1763, BGB-21447, BR101801, AC676, ATA3219, ABBV-319, ABBV-101, ICP-B02, ICP-B05, C-CAR039, Efineptakin Alfa, and others. Dive deep into rich insights for new drugs for follicular lymphoma treatment, visit @ Follicular Lymphoma Drugs Table of Contents For further information on the follicular lymphoma pipeline therapeutics, reach out @ Follicular Lymphoma Treatment Drugs Related Reports Follicular Lymphoma Market Follicular Lymphoma Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key follicular lymphoma companies including Epizyme, Eisai, Bayer Healthcare Pharmaceuticals, Verastem Oncology, Gilead Sciences, TG Therapeutics, Bristol-Myers-Squibb, Roche, Incyte Corporation, Bristol Myers Squibb, ADC Therapeutics, MorphoSys, Nordic Nanovector, AbbVie, Regeneron Pharmaceuticals, Janssen Research & Development, Novartis, MEI Pharma, and BeiGene, among others. Non-Hodgkin Lymphoma Market Non-Hodgkin Lymphoma Market Insights, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key Non-Hodgkin lymphoma companies, including Roche, Pfizer, Amgen, Novartis, Teva Pharmaceuticals, Genentech, ACD Therapeutics, among others. Non-Hodgkin Lymphoma Pipeline Non-Hodgkin Lymphoma Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key Non-Hodgkin lymphoma companies, including Novartis, AstraZeneca, Genentech, BioInvent, Genmab, SystImmune, Nordic Nanovector, Pacylex Pharmaceuticals, Artiva Biotherapeutics, Inc., Chipscreen Biosciences, Ltd., Timmune Biotech Inc., Chia Tai Tianqing Pharmaceutical Group Co., Ltd., Gilead Sciences, Acerta Pharma BV, Adagene Inc, Conjupro Biotherapeutics, Inc., Rhizen Pharmaceuticals, Juventas Cell Therapy Ltd., Incyte Corporation, HUYA Bioscience International, SecuraBio, Genor Biopharma Co., Ltd., Kyowa Kirin Co., Ltd., Antengene Therapeutics Limited, Regeneron Pharmaceuticals, Jiangsu HengRui Medicine Co., Ltd., Xynomic Pharmaceuticals, Inc., BioTheryX, Inc., UWELL Biopharma, Kronos Bio, Bio-Thera Solutions, Spectrum Pharmaceuticals, Inc., Aptose Biosciences Inc., Miltenyi Biomedicine GmbH, Precision BioSciences, Inc., Teneobio, Inc., TCR2 Therapeutics, IGM Biosciences, Inc, among others. Diffuse Large B-cell Lymphoma Market Diffuse Large B-cell Lymphoma Market Insights, Epidemiology, and Market Forecast – 2034 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key DLBCL companies, including AbbVie, Genmab, Merck, Roche, Xencor, Janssen, Denovo Biopharma, Calithera Biosciences IMV, Biogen, Autolus Therapeutics, Allogene Therapeutics, Novartis, Miltenyi Biomedicine, Regeneron Pharmaceuticals, Debiopharm, Seagen, Takeda, AstraZeneca, Gilead Sciences, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . 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An Oncology biotech pioneering RAD51 inhibition and other DDR mechanisms Home Science Team Pipeline News Careers Contact Us Home Science Team Pipeline News Careers Contact Us Home Science Team Pipeline News Careers Contact Us November 21, 2024 12:38 pm Satya Pharma and Alivexis have discovered a highly selective, safe and best-in-class PKMYT1 inhibitor for CCNE-1 amplified and other bio-marker identified tumors Satyarx Pharma Innovations Private Limited (“Satya Pharma”), an oncology biotech, and Alivexis, Inc. (formerly known as Modulus Discovery, Inc.), a global biotech company based in Japan and Boston, USA, entered into a preclinical collaboration in May 2023 to develop a best-in-class PKMYT1 inhibitor. Under the terms of the agreement, the companies co-funded and developed a pre-clinical candidate selectively targeting PKMYT-1, while sparing Wee1 and other related proteins. PKMYT1 inhibitors are a novel class of therapeutics designed to target CCNE1-amplified cancers, a significant unmet medical need. This uniquely structured collaboration drew on the collective expertise of Satya and Alivexis, including Alivexis’ Intelligent Supercomputing capabilities and the experienced drug discovery team at Satya The candidate and backup compounds are distinct from other reported compounds in terms of selectivity over Wee1 and related kinases, resulting in excellent efficacy, significantly improved safety and druggability. Furthermore, the wide therapeutic window exhibited in preclinical studies highlights the potential of the molecule to be used either as a single agent or in combination with existing standard or care drugs across selected cancers The program, now part of Alivexis portfolio (ALVX-A), is available for partnering About Satya Pharma Satya was started in Aug 2020 as an oncology biotech. It is focused on DDR pathways and on developing therapeutics that are First-in-class or with a novel mode of binding. Satya’s objective is to discover drugs with the potential to address cancers by directly targeting important biological pathways implicated in oncogenesis or resistance mechanisms, thereby presenting novel and high-impact opportunities for treatment across indications. About Alivexis Alivexis, Inc. is a technology-driven drug discovery enterprise with operational foundations in both Japan and the US. By merging state-of-the-art drug discovery platforms including ModBindTM, which is a highly accelerated accurate and absolute simulation method, with profound knowledge of disease biology and a dynamic global business approach, Alivexis is propelling forward a distinct portfolio of small molecule drugs along with a variety of research and development collaborations. At present, Alivexis is dedicated to swiftly bringing innovative medications to individuals and their families grappling with cancer, both chronic and acute immune-inflammatory conditions, and rare diseases. Recently out-licensed its Cathepsin C clinical candidate developed for neutrophil-driven inflammatory disorders to Melodia Therapeutics for a value of upto 245 million USD. Managed by a team with broad experience across pharmaceutical and biotech sectors in Japan and the U.S., Alivexis embodies a collaborative, network-based approach to drug discovery.