logo
Scientists Recreated The Ancient Chemical Reactions That May Have Sparked Life

Scientists Recreated The Ancient Chemical Reactions That May Have Sparked Life

Yahoo17-05-2025

Life on Earth probably began in warm, underwater 'chemical gardens', rich in hydrogen and iron. Researchers from Germany have now simulated this environment in a vial, and found that archaic life forms that live in the deep sea today can thrive under these primordial conditions.
It's difficult to imagine how life kicked off on our planet. In ecosystems today, life is so deeply entwined with itself that very few creatures live directly off Earth's raw materials. That has been the case for a very, very long time.
But the first organisms on an otherwise lifeless planet would have had to make do with what the mineral environment had to offer. There was little to no oxygen, and no photosynthesis. As you can see in the video below, some deep sea organisms still live this way, surviving on hydrothermal vents at depths where the sun don't shine.
Borrowing electrons from hydrogen as it spews from the Earth's core, the deep-sea microbes follow a recipe more ancient than the genes they use to conduct it, called the acetyl CoA pathway. It is the only method for carbon fixation – processing inorganic carbon into organic compounds – that can be re-created without enzymes.
But when this recipe was first written, in Earth's early years, seawater contained a whole lot more dissolved iron than it does today. A team led by geochemist Vanessa Helmbrecht of Ludwig Maximilian University of Munich in Germany wanted to test how much of a difference this dissolved iron would have made, by simulating these ancient ocean conditions in the lab.
"The ancient occurrence of hydrothermal iron-sulfide rich deposits in the geological record extend into the early Archaean eon (4 to 3.6 billion years ago) and exhibit fossil features interpreted as some of the oldest signatures for life on Earth," the team writes in their paper describing the experiment.
"However, links between abiotic H2 [dihydrogen] production in iron-sulfide chemical gardens simulating [primordial] hydrothermal systems and early life are scarce."
A single-celled microbe of the order archaea, Methanocaldococcus jannaschii, was selected as the test subject for these simulations. It was first collected from a hydrothermal vent off the western coast of Mexico, where, using the acetyl CoA pathway, it relies on carbon dioxide and hydrogen as its primary sources of energy.
"Abiotic H2 was a potentially important electron donor and CO2 served as a key electron acceptor for the first cells," the team explains. "Anaerobic organisms that use the H2-dependent reductive acetyl CoA pathway for CO2 fixation are modern representatives that have preserved vestiges of the first metabolisms."
The experiments placed M. jannaschii into a miniature version of the deep sea hydrothermal vents, neatly contained in a glass vial. By injecting sulfidic fluid into water devoid of dissolved oxygen, they formed a black precipitate that grew into a chimney structure within 5-10 minutes.
At high temperatures, the iron and sulfur in this microcosm formed the iron sulfide minerals mackinawite (FeS) and greigite (Fe3S4). When iron sulfide is hydrated, H2 is released.
Though quite different from its modern home, M. jannaschii thrived in this strange environment.
"At the beginning, we expected only slight growth, as we did not add any extra nutrients, vitamins, or trace metals to the experiment," Helmbrecht says. "As well as over-expressing some genes of the acetyl CoA metabolism, the archaeans actually grew exponentially."
The M. jannaschii cells tended to hang out right beside the mackinawite particles, in a scene much like some of the earliest traces of life found in fossil specimens. These chemical gardens, the scientists think, fuelled Earth's first microbes.
This is evidence that the recipe for acetyl CoA metabolism emerged from the extreme and energy-limited environments where Earth life may have struck its first sparks.
"Our study points to mackinawite and greigite chemical gardens as potential hatcheries of life, primordial environments that could theoretically support a continuous evolution of the first metabolizing cells," the authors conclude.
The research is published in Nature Ecology & Evolution.
Mystery of T. Rex's Debated North American Origins Finally Solved
Wild Chimps Appear to Administer 'First Aid' to Each Other
Scientists Discover Oldest Reptile Tracks, Rewriting Evolution Timeline

Orange background

Try Our AI Features

Explore what Daily8 AI can do for you:

Comments

No comments yet...

Related Articles

Press Release: ASCO: new Sarclisa data support subcutaneous administration with on-body injector
Press Release: ASCO: new Sarclisa data support subcutaneous administration with on-body injector

Associated Press

timean hour ago

  • Associated Press

Press Release: ASCO: new Sarclisa data support subcutaneous administration with on-body injector

ASCO: new Sarclisa data support subcutaneous administration with on-body injector Paris, June 3, 2025. New data from two clinical studies of the investigational use of Sarclisa administered subcutaneously (SC) via an on-body injector (OBI) (also referred to as an on-body delivery system) in relapsed or refractory multiple myeloma (R/R MM) support the potential use of this innovative delivery method to advance patient care, while upholding Sarclisa's efficacy and safety profile. The results were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting and include full data from the IRAKLIA phase 3 study, the first to incorporate the use of an OBI in the treatment of MM, and demonstrate non-inferior efficacy and pharmacokinetics compared to Sarclisa intravenous (IV) infusion. Alyssa Johnsen, MD, PhD Global Therapeutic Area Head, Immunology and Oncology Development 'Our subcutaneous clinical program is rooted in our mission to address patient needs and reduce treatment burden in multiple myeloma. We believe the novel on-body injector represents a significant innovation thatcouldimprove and streamline the treatment process for both patients and providers. We are pleased to share thesedata, the first to evaluate an on-body injector with a multiple myeloma treatment, and look forwardtopotentiallybringing this formulation and administrationoptionto the multiple myeloma community.' The OBI offers the potential to improve the overall patient experience in MM treatment. Recent studies and surveys suggest the use of an OBI may be associated with greater convenience, flexibility, and patient satisfaction compared to IV or manual SC administration methods.1 In addition, an OBI may also streamline the administration process for providers, potentially reducing the physical burden on nurses and enabling them to possibly move freely through the use of a hands-free device while monitoring the patient during injection. The IRAKLIA phase 3 study and the IZALCO phase 2 study presented at ASCO were conducted using Enable Injections' enFuse® hands-free OBI, an automated injector designed to subcutaneously administer high-volume medicines beginning with the click of a button, to administer the hyaluronidase-free SC formulation of Sarclisa. The enFuse device uses a 30 gauge, hidden, and retractable needle that is smaller compared to some of the commonly used large-volume SC injection needles, which may support patient comfort. The safety and efficacy of Sarclisa SC administered with the OBI or manual administration are investigational and have not been approved for use by any regulatory authority. IRAKLIA phase 3 study IRAKLIA is a global, randomized, open-label, pivotal phase 3 non-inferiority study comparing Sarclisa SC administered via an OBI and Sarclisa IV, both in combination with pomalidomide and dexamethasone (Pd) in adult patients with R/R MM who have received at least one prior line of treatment. At the data cut-off of November 6, 2024, and a median follow-up of 12 months, the study demonstrated: Primary endpoints Secondary endpoints The overall safety profile of Sarclisa SC-Pd observed in this study was consistent with the established safety profile of Sarclisa IV-Pd, but with a notably lower rate of systemic IRs. No new safety concerns were observed, except for low-grade local injection site reactions (ISRs) associated with SC administration that occurred with a low incidence (0.4%, n=19/5,145 injections). Nearly all ISRs were grade 1, except for one episode of grade 2. Xavier Leleu, MD, PhD Head of the Department of Hematology and Myeloma Clinic at the Hôpital La Mileterie and study investigator 'Results from the IRAKLIA phase 3 study represent a potentially transformational advancement in the administration of multiple myeloma treatment. These data not only establish non-inferiority between Sarclisa administered both subcutaneously and intravenously across several key endpoints but reinforce the positive impact that this on-body injector could have on the patient treatment experience, as demonstrated by patient satisfaction scores.' In addition to the oral presentation at ASCO, the full data were simultaneously published in the Journal of Clinical Oncology. IZALCO phase 2 study In addition to the IRAKLIA phase 3 study, Sanofi also presented new data from the randomized, sequential, open-label, IZALCO phase 2 study evaluating the efficacy and safety of Sarclisa SC administered via manual push or an OBI, in combination with carfilzomib and dexamethasone (Kd) in adult patients with R/R MM who have received one to three prior lines of therapy. At a median follow-up of 10.1 months, the study demonstrated: The overall safety profile of Sarclisa SC-Kd observed in this study was consistent with the established safety profile of Sarclisa IV-Kd, with no new safety concerns observed. Advancing patient and provider-centric innovation in MM While SC administration is currently available for certain MM treatment regimens through a manual injection, administering large-volume medicines manually can present significant challenges, including a labor-intensive process for nurses, risk of strain and needlestick injuries, and potential need for larger needles that may compromise patient comfort and increase anxiety. Mehul Desai, PharmD, MBA Vice President, Medical Affairs, Enable Injections 'We believe multiple myeloma patients deserve a more convenient and comfortable treatment experience and recognize the crucial role providers play in delivering that care. Through our collaboration with Sanofi, we've aspired to advance an on-body injector that could transform the treatment experience for patients and providers alike. The results from the IRAKLIA and IZALCO studies represent a significant step toward our ambition and validate the potential of the on-body injector to deliver the same high standard of efficacy established with intravenous Sarclisa.' In addition to IRAKLIA and IZALCO, Sanofi is also evaluating Sarclisa SC administration via an OBI in the front-line treatment setting. The ISASOCUT phase 2 study conducted by the University of Poitiers, is evaluating Sarclisa in combination with bortezomib, lenalidomide and dexamethasone (VRd) in adult patients with newly diagnosed MM (NDMM) not eligible for autologous stem-cell transplant (ASCT), while the German-speaking Myeloma Multicenter Group (GMMG)-HD8 phase 3 study, conducted in collaboration with the GMMG and the German Multiple Myeloma Study Group Consortium (DSMM), is evaluating Sarclisa SC-VRd induction in NDMM patients who are eligible for ASCT. In addition, results from the IZALCO, IRAKLIA and ISASOCUT studies will be presented at the European Hematology Association Congress later this month. The IRAKLIA abstract was also hand-selected to be included in the 2025 Best of ASCO program, held later in the summer of 2025, following the ASCO Annual Meeting. The data from these studies, collectively, will form the basis for global regulatory submissions. Sarclisa administered subcutaneously via the on-body injector or manual administration is investigational and has not been approved for any use by any regulatory authority. The safety and efficacy of this formulation and delivery method have not been established. About the IRAKLIA and IZALCO studies IRAKLIA is a randomized, open-label, pivotal phase 3 study evaluating the non-inferiority of Sarclisa SC formulation administered at a fixed dose SC via an OBI versus weight-based dosed Sarclisa IV in combination with Pd in adult patients with R/R MM who have received at least one prior line of therapy. The co-primary outcomes being assessed are ORR, defined as the proportion of patients with stringent CR, CR, VGPR, and partial response (PR) according to the 2016 IMWG criteria assessed by Independent Review Committee (IRC), and observed C trough at steady state (pre-dose at C6D1), defined as observed Sarclisa plasma concentrations. IZALCO is a two-part, randomized, sequential, open-label, phase 2 study evaluating the efficacy and safety of Sarclisa SC formulation administered SC via manual push or an OBI in adult patients with R/R MM who have received one to three prior lines of therapy. The primary objective is ORR, as assessed by IRC. The secondary objective is patient preference for the OBI versus manual administration of Sarclisa SC. About Enable Injections Based in the US (Cincinnati, OH), Enable Injections is a global healthcare innovation company committed to improving the patient treatment experience through the development and manufacturing of enFuse. enFuse is an innovative wearable drug delivery platform that is designed to deliver large volumes of pharmaceutical and biologic therapeutics via subcutaneous administration, with the aim of improving convenience, supporting superior outcomes, and advancing healthcare system economics. For more information, visit About Sarclisa Sarclisa (isatuximab) is approved in more than 50 countries, including in the US, EU, Japan, and China, across multiple treatment lines for MM. Based on the ICARIA-MM phase 3 study, Sarclisa is approved in the US, EU and Japan in combination with Pd for the treatment of patients with R/R MM who have received ≥two prior therapies, including lenalidomide and a proteasome inhibitor and have relapsed on the last therapy; this combination is also approved in China for patients who have received at least one prior line of therapy, including lenalidomide and a proteasome inhibitor. Based on the IKEMA phase 3 study, Sarclisa is also approved in more than 50 countries in combination with carfilzomib and dexamethasone, including in the US for the treatment of patients with R/R MM who have received one to three prior lines of therapy and in the EU for patients with MM who have received at least one prior therapy. In the US, EU, UK, and China, Sarclisa is approved in combination with VRd as a front-line treatment option in transplant-ineligible NDMM patients, based on the IMROZ phase 3 study. In Japan, Sarclisa is approved in combination with VRd as a front-line treatment option regardless of transplant eligibility. At Sanofi, we are building on a long-standing commitment to oncology as we continue to chase the miracles of science to improve the lives of those living with cancer. We are committed to transforming cancer care by developing innovative, first and best-in-class immunological and targeted therapies for rare and difficult-to-treat cancers with high unmet need. For more information on Sarclisa clinical studies, please visit About Sanofi Sanofi is an R&D driven, AI-powered biopharma company committed to improving people's lives and creating compelling growth. We apply our deep understanding of the immune system to invent medicines and vaccines that treat and protect millions of people around the world, with an innovative pipeline that could benefit millions more. Our team is guided by one purpose: we chase the miracles of science to improve people's lives; this inspires us to drive progress and deliver positive impact for our people and the communities we serve, by addressing the most urgent healthcare, environmental, and societal challenges of our time. Sanofi is listed on EURONEXT: SAN and NASDAQ: SNY Media Relations Sandrine Guendoul | +33 6 25 09 14 25 | [email protected] Evan Berland | +1 215 432 0234 | [email protected] Léo Le Bourhis | +33 6 75 06 43 81 | [email protected] Victor Rouault | +33 6 70 93 71 40 | [email protected] Timothy Gilbert | +1 516 521 2929 | [email protected] Investor Relations Thomas Kudsk Larsen |+44 7545 513 693 | [email protected] Alizé Kaisserian | +33 6 47 04 12 11 | [email protected] Felix Lauscher | +1 908 612 7239 | [email protected] Keita Browne | +1 781 249 1766 | [email protected] Nathalie Pham | +33 7 85 93 30 17 | [email protected] Tarik Elgoutni | +1 617 710 3587 | [email protected] Thibaud Châtelet | +33 6 80 80 89 90 | [email protected] Yun Li | +33 6 84 00 90 72 | [email protected] Sanofi forward-looking statements All trademarks mentioned in this press release are the property of the Sanofi group with the exception of enFuse. Attachment

Behind History's Icons II: Hitler's Jaw and Cold War Secrets
Behind History's Icons II: Hitler's Jaw and Cold War Secrets

Medscape

time4 hours ago

  • Medscape

Behind History's Icons II: Hitler's Jaw and Cold War Secrets

Ancient Egyptians believed that mummifying a king's body was key to his ascent into the realm of the gods. The preserved body, known as the Ach, a luminous spirit, was thought to begin this journey by entering the sarcophagus, seen as the womb of Nut, the mother goddess of the sky. The belief in the enduring power of human remains has been deep in global history. In the West, reverence for the relics of Christian saints took place early in the Church. Some of the most extraordinary examples include what was believed to be the foreskin of Jesus and the severed head of Saint John the Baptist. By the 19th century, European scientists had begun preserving and studying body parts of famous individuals — from Mohammed's beard and Buddha's teeth to Adolf Hitler's jaw. Following the Napoleon relics story, Part II probes Hitler's preserved jaws. Hitler's Final Days It was April 28, 1945. Hitler, 1889-1945, Germany's leader, paced furiously through the corridors of the Wolf's Lair, his secret headquarters near Rastenburg, close to Görlitz. He was furious, as his trusted deputy head of the Nazi Party's paramilitary force, Heinrich Himmler is believed to have been betrayed by Hitler for several months. He reportedly held secret talks with Western Allies to end the war. Shockingly, he is said to have offered to halt the Holocaust of Hungarian Jews if Americans — Germany's main enemy in the West — would ease their attacks. Hitler was reportedly stunned. In an effort to regain his composure, Hitler summons Hermann Fegelein — 1906-1945, his liaison to the Waffen Schutzstaffel, the Nazi Party's armed military unit responsible for combat operations. According to these reports, Hitler ordered their execution. Another report stated that he ordered his arrest and left the execution order to his subordinates. Himmler, in turn, expels Hitler from the Nazi Party and removes him from all party and state positions. However, in reality, Hitler was more composed than he appeared. As often in his life, even moments of lost composure serve a greater purpose. Historian and Himmler biographer Heinz Peter Longerich noted that just one week before his public outburst on April 22, 1945, Hitler privately declared that he would stop issuing orders. This was his way of signaling to his top officials that the war was lost. By this point, Hitler had effectively lost control over his army. Obergruppenführer Felix Steiner, 1896-1966, had earlier refused to carry out a relief attack ordered by Hitler during the Battle of Berlin, calling it impossible. To avoid being linked to inevitable and shameful defeat, Hitler allowed others to handle peace negotiations and then publicly expelled them from the Nazi Party. Historians widely agree that Hitler decided to take his own life on April 27, 1945, one day before his outburst. When news of Himmler's betrayal became known, Hitler acted quickly and decisively. He first expelled Himmler from the party and then, by proxy, took revenge on Fegelein. Just before midnight, Hitler hurriedly married his partner, Eva Braun in 1912-1945. He then dictated his political and personal will to his secretary, Traudl Junge in 1920-2002. On the morning of April 30, Hitler tested poison ampoules on his German shepherd and later gave a similar poison to his colleagues. At approximately 3:30 PM, he had Braun swallow cyanide before shooting. However, myths and uncertainties surround what occurred next. Corpse Odyssey Hitler's death did not end speculation. Conspiracy theories quickly surfaced, claiming that he had faked his death and fled abroad, possibly to Argentina or Japan, with the help of body doubles and plastic surgery. According to conspiracy theories, Hitler fired a double shot and burned his body beyond recognition before escaping the submarine to Argentina or Japan. These theories claim that his outbursts of rage, will, distribution of poison vials, and suicide were staged. Until recently, Hitler was said to have lived a privileged life abroad, even after undergoing surgical alterations. Local historian and biographer Harald Sandner calls this 'humbug.' He pointed out that Hitler's body was examined multiple times by experts and moved at least 10 times. According to the report, Hitler and Braun's bodies were carried into the Reich Chancellery Garden at approximately 3:50 PM on April 30, 1945. The individuals who carried the bodies into the garden included Hitler's valet Heinz Linge, Criminal Director Peter Högl, Hauptsturmführer Ewald Lindloff, and Obersturmführer Heinrich Josef Reiser. The bodies were then doused with gasoline and set on fire. Eyewitness accounts, including that of Rottenführer Hermann Karnau, mentioned that between 4 and 6:20 PM, the remains showed movement described as 'the flesh moved up and down,' which is consistent with the natural effects of burning human bodies and muscle contractions during cremation. On May 4, Soviet soldiers found the remains, initially unaware of their significance. The next day, the bodies were reburied and moved to Helios Hospital Berlin-Buch, where autopsies were performed on May 8. Fritz Echtmann, longtime assistant to Hitler's dentist Hugo Johannes Blaschke, 1881-1959, may be for propaganda reasons, confirmed the identity of Hitler's jaw remains as unclear. However, Soviet authorities promoted the narrative that Hitler had cowardly taken poison, rejecting the evidence that he had also shot himself, and confirmed the authenticity of the jaws. Soviet doctors later claimed Hitler had 'cowardly poisoned himself instead of heroically shooting himself.' On May 4, 1945, Soviet troops from the 3rd Shock Army discovered these bodies. Unaware that they belonged to Adolf and Eva Hitler, they wrapped them in blankets and buried them. On May 5, the next day, other Soviet soldiers found the bodies again and transported them in an ammunition box to the Pathological Institute at Helios Hospital Berlin-Buch. The bodies were autopsied between May 8 and May 10. Echtmann confirmed the authenticity of Hitler's jaw. For propaganda purposes, Soviet doctors later claimed that Hitler had 'cowardly poisoned himself instead of heroically shooting himself.' Even decades later, in 1968, the well-known Russian journalist and military history professor Lev Aleksandrovich Bezymensky in 1920-2007 wrote that Hitler's charred corpse smelled of bitter almonds. In the second half of May 1945, grave robbers opened Hitler's grave, searching for a rumored Nazi treasure said to be buried with him. Soviet soldiers protected the bodies and moved them again, in ammunition crates, to Finow, 38 km away, where they were reburied. On May 22, 1945, the body was exhumed and reburied for unknown reasons. Forensic Investigation On June 9, 1945, Marshal of the Soviet Union Georgy Konstantinovich Zhukov in 1896-1974 claimed that Hitler's death was uncertain. British historian Sir Richard John Evans suggested that the Soviet Union might have wanted to maintain the threat of Hitler's survival to justify a harsh occupation policy. Consequently, false information about Hitler's death is deliberately disseminated. This theory is supported by the fact that Hitler's suicide was reported in the Soviet newspaper Krasnaya Zvezda on May 10, 1945. As late as June 5, Soviet Army officers confirmed this to American officers. Probably on orders from Joseph Vissarionovich Stalin in 1878-1953 denials began just 4 days later. On June 7, 1945, the bodies of Adolf and Eva Hitler were reportedly brought to Rathenau in a 'half-rotten state.' Between December 8, 1945, and January 13, 1946, Soviet Colonel General Bogdan Zakharovich Kobulov ordered a new examination of Hitler's body. To prevent this investigation, other Soviet officials arranged for the bodies to move to Magdeburg, Germany. Once again, the bodies were buried in ammunition crates in a 2 m deep pit in the courtyard of Westendstraße 32 (now Klausenerstraße 32). On February 21, 1946, the bodies were autopsied. They were then buried in the courtyard of a Soviet military settlement beneath an 18 cm thick concrete slab. On April 5, 1970, the KGB, a highly centralized and secretive organization Chief Yuri Vladimirovich Andropov, 1914-1984, ordered the bodies to be destroyed. The military settlement was to be handed over to the East German authorities, and Andropov did not want to risk the bodies falling into their hands. Among historians, Sandner's accounts are valued but are not fully reliable. Sandner, who had never received formal training in history, did not provide detailed annotations in his books to clarify his reasoning. A publication by the French forensic scientist and pathologist Philippe Charlier in the European Journal of Internal Medicine is considered scientifically credible. Charlier reported that the Russian domestic intelligence service (Federal Security Service) allowed him and his team to examine Hitler's presumed skull and dentures, which had survived the final burning. Their investigation confirmed that the dentures belonged to Hitler. However, they were not 100% certain about the skull, which showed traces of a gunshot wound. These findings align with the report of German forensic biologist Mark Benecke, who was permitted to examine Hitler's alleged remains for a week in November 2001. Benecke wrote at the time: 'There is no doubt about the authenticity of the teeth. Hitler had a unique dental structure. He used a large metal bridge in 1944. Using old x-rays, I was able to clearly identify the teeth as Hitler's.' However, Benecke found no traces of poison or glass fragments in the ampoule. Surprised, he consulted Bezymensky. 'Bezymensky told me that the KGB had only allowed him to publish his book in 1986 on one condition: That he would support the poison theory,' Benecke wrote about his conversation with Bezymensky. Finally, the alleged fragment of Hitler's skull was stored in a plastic box, which was intended for computer disks. According to contemporary historian Joachim Fest in 1926-2006, Hitler's body was found 'slumped over,' with 'his head slightly bent forward…on the flowered sofa,' after he had shot a coin-sized hole in his temple with a pistol. If this description is correct, the skull fragment could not belong to Hitler. The entry and exit wounds suggest the shot came from below, most likely fired 'in the mouth.' To confirm identity, the remaining blood traces must be examined. However, Benecke stated that he would require comparative DNA from Hitler's relatives, such as his sister, who was buried near Munich. Exhumation is the only method to obtain genetic material. Conclusion Few other deaths are surrounded by myths similar to Hitler's death. The search for the truth about Hitler's death is complicated by the competing interests and the interests of those with partial knowledge. Historians now agree that Hitler died by suicide on April 30, 1945, either by shooting himself or by combining gunshots with poison. Scientific evidence confirms that Hitler's dentures are preserved and currently held by Russian domestic intelligence services. Whether the skull in the Russian State Archives belonged to him remains unclear.

Relacorilant + Nab-Paclitaxel Beneficial in Ovarian Cancer
Relacorilant + Nab-Paclitaxel Beneficial in Ovarian Cancer

Medscape

time5 hours ago

  • Medscape

Relacorilant + Nab-Paclitaxel Beneficial in Ovarian Cancer

Relacorilant, a selective glucocorticoid receptor antagonist, combined with nab-paclitaxel significantly improved progression-free survival in women with platinum-resistant ovarian cancer. The interim analysis also showed meaningful improvement in overall survival, with median survival extending from 11.50 to 15.97 months. METHODOLOGY: While platinum-based chemotherapy is initially effective, about 70% of patients experience disease relapse that becomes platinum-resistant. Relacorilant, a selective glucocorticoid receptor antagonist, has demonstrated synergy with paclitaxel in nonclinical tumor models. The combination with nab-paclitaxel was chosen for this study because it does not require corticosteroid coadministration. Researchers conducted a randomized, controlled, open-label, phase 3 trial (ROSELLA [GOG-3073/ENGOT-ov72]) at 117 hospitals and community oncology treatment centers across 14 countries in Australia, Europe, Latin America, North America, and South Korea. Participants included 381 patients aged 18 years or older with confirmed platinum-resistant epithelial ovarian, primary peritoneal, or fallopian tube cancer; up to three previous lines of anticancer therapy; and measurable disease as per Response Evaluation Criteria in Solid Tumors (version 1.1). Analysis involved comparing relacorilant (150 mg orally the day before, of, and after nab-paclitaxel infusion) plus nab-paclitaxel (80 mg/m2 intravenously on days 1, 8, and 15 of each 28-day cycle) with nab-paclitaxel monotherapy (100 mg/m2 on the same schedule). TAKEAWAY: Patients receiving relacorilant plus nab-paclitaxel showed improved progression-free survival compared with those receiving nab-paclitaxel monotherapy (hazard ratio [HR], 0.70; 95% CI, 0.54-0.91; median, 6.54 months vs 5.52 months; stratified log-rank P = .0076). = .0076). Interim analysis revealed improved overall survival with relacorilant plus nab-paclitaxel vs nab-paclitaxel monotherapy (HR, 0.69; 95% CI, 0.52-0.92; median, 15.97 months vs 11.50 months; log-rank P = .0121). = .0121). Safety profiles were comparable between the groups when adjusted for nab-paclitaxel exposure, with no new safety signals observed. IN PRACTICE: 'Combined with the evidence from previous studies, our study supports relacorilant plus nab-paclitaxel as a potential new standard of care for patients with platinum-resistant ovarian cancer, without the need for biomarker selection. This study is the first positive clinical trial conducted with registrational intent for a selective glucocorticoid receptor antagonist in patients with cancer,' authors of the study wrote. SOURCE: Lead author Alexander B. Olawaiye, MD, of the University of Pittsburgh School of Medicine and UPMC Magee-Womens Hospital, both in Pittsburgh, presented the results of the study at American Society of Clinical Oncology (ASCO) 2025. A paper on the study was published online in The Lancet on June 2. LIMITATIONS: The open-label design and applicability to patients with more than three lines of anticancer therapy were noted as limitations. While the risk of bias in progression-free survival assessment was mitigated by using blinded independent central review and a dual primary endpoint of overall survival, the median duration of the follow-up for overall survival was less than the estimated median overall survival in the relacorilant combination group at interim analysis. DISCLOSURES: The study was funded by Corcept Therapeutics. The authors reported that adverse events were graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (version 5.0), with relatedness determined by the investigators. The funding source supported trial conduct, patient enrollment, and drug supply. The analysis, interpretation, writing, and submission decisions were the responsibility of the authors.

DOWNLOAD THE APP

Get Started Now: Download the App

Ready to dive into the world of global news and events? Download our app today from your preferred app store and start exploring.
app-storeplay-store