RMC-6236 (Daraxonrasib): A New Chapter of Hope for Patients with KRAS-Mutated Pancreatic Cancer RMC-6236（Daraxonrasib）：KRAS 突变胰腺癌患者的新希望

For decades, pancreatic cancer has remained one of the most devastating diagnoses in oncology. Despite remarkable advances in cancer treatment, patients with pancreatic ductal adenocarcinoma (PDAC)—the most common form of pancreatic cancer—continue to face poor survival outcomes. The disease is often diagnosed at an advanced stage, spreads rapidly, and responds only modestly to conventional chemotherapy. For many patients and their families, treatment options have been limited, and hope has often been overshadowed by the aggressive nature of this disease. (几十年来，胰腺癌一直被认为是肿瘤学领域最具挑战性的恶性肿瘤之一。尽管癌症治疗取得了显著进步，但胰腺导管腺癌（Pancreatic Ductal Adenocarcinoma，PDAC）——最常见的胰腺癌类型——患者的生存率仍然较低。由于该疾病通常在晚期才被确诊，进展迅速，并且对传统化疗的疗效有限，因此患者及其家属长期面临治疗选择有限、预后不佳的困境。)

Today, however, the landscape is beginning to change. (如今，这一局面正开始发生改变。)

Among the most promising developments is Daraxonrasib (RMC-6236), an investigational oral targeted therapy designed to inhibit multiple cancer-driving RAS proteins. Unlike earlier targeted therapies that are effective only against specific KRAS mutations, RMC-6236 is being developed as a pan-RAS(ON) inhibitor, capable of targeting multiple activated RAS variants. Although the drug remains under clinical investigation, recent clinical trial results have generated considerable excitement within the oncology community, suggesting that RMC-6236 may represent one of the most important advances in pancreatic cancer treatment in recent years. (其中最受关注的创新疗法之一是 Daraxonrasib（RMC-6236）。这是一种正在临床研究中的口服靶向药物，旨在抑制多种致癌性 RAS 蛋白。与仅针对某一种 KRAS 突变的靶向药不同，RMC-6236 被设计为一种 泛 RAS（ON）抑制剂（Pan-RAS(ON) inhibitor），能够同时作用于多种处于活化状态的 RAS 突变体。虽然该药物目前仍处于临床研究阶段，但近期公布的临床试验结果已在全球肿瘤学界引起广泛关注，并显示出其有望成为近年来胰腺癌精准治疗领域最具突破性的创新疗法之一。)

This article provides an overview of the scientific rationale behind RMC-6236, explains why targeting the RAS signaling pathway has become a major focus of modern cancer research, and summarizes the latest clinical evidence supporting its potential role in the treatment of pancreatic cancer. Written in an accessible style, it aims to help healthcare professionals, patients, and their families better understand the significance of this emerging therapy and its potential impact on the future of precision oncology. (本文将介绍 RMC-6236 的研发背景及其科学依据，阐述为何 RAS 信号通路已成为现代肿瘤精准治疗的重要研究方向，并总结目前支持其临床应用前景的主要研究证据。文章采用通俗易懂而又兼具科学严谨性的写作方式，希望帮助医务人员、患者及其家属更好地理解这一新型靶向治疗策略及其在未来精准肿瘤治疗中的潜在价值。)

Why Is Pancreatic Cancer So Difficult to Treat? (为什么胰腺癌如此难以治疗？)

Approximately 90–95% of pancreatic ductal adenocarcinomas (PDAC) harbor mutations in the KRAS gene, making KRAS the principal molecular driver of this disease. KRAS acts as a molecular "switch" that regulates cell growth, division, and survival. Under normal conditions, this switch is turned on only when cells receive appropriate growth signals and is switched off once its function is completed. In pancreatic cancer, however, KRAS mutations lock this molecular switch permanently in the "on" position, leading to continuous cell proliferation, uncontrolled tumor growth, and resistance to normal cell death. (约 90%–95% 的胰腺导管腺癌（PDAC）存在 KRAS 基因突变，因此 KRAS 被认为是驱动该疾病发生和发展的核心分子。KRAS 就像细胞内的一个“分子开关”，负责调控细胞的生长、分裂和存活。在正常情况下，这个开关只有在细胞接收到生长信号时才会开启，完成任务后又会自动关闭。然而，在胰腺癌中，KRAS 突变使这一“开关”长期处于持续激活状态，导致肿瘤细胞不断增殖、生长失控，并逃避正常的细胞凋亡机制。)

This persistent activation also stimulates several downstream signaling pathways—including the RAF–MEK–ERK and PI3K–AKT–mTOR pathways—that collectively promote tumor progression, metastasis, metabolic reprogramming, and resistance to chemotherapy. Consequently, mutant KRAS has long been regarded as the "engine" that drives pancreatic cancer. (持续激活的 KRAS 还会进一步启动多条重要的下游信号通路，包括 RAF–MEK–ERK 和 PI3K–AKT–mTOR 通路。这些信号网络共同促进肿瘤生长、远处转移、代谢重编程以及对化疗的耐药。因此，KRAS 常被形象地称为驱动胰腺癌发展的“发动机”。)

Although researchers discovered the importance of KRAS more than four decades ago, directly targeting this protein proved extraordinarily difficult. Unlike many other proteins successfully targeted by modern medicines, KRAS possesses a relatively smooth molecular surface with few suitable binding pockets for small-molecule drugs. In addition, KRAS binds very tightly to its natural substrates, making it extremely challenging for therapeutic molecules to compete effectively. For these reasons, KRAS earned the reputation of being one of the most "undruggable" targets in cancer biology. (尽管科学家早在四十多年前就认识到 KRAS 在肿瘤中的关键作用，但直接靶向这一蛋白却异常困难。与许多已经成功实现药物靶向的蛋白不同，KRAS 的蛋白结构表面较为平滑，缺乏适合小分子药物结合的“口袋”，同时它与天然底物结合能力极强，使药物难以有效竞争。因此，KRAS 长期以来一直被认为是肿瘤学领域最具挑战性的“不可成药（Undruggable）”靶点之一。)

A major breakthrough occurred with the development of KRAS G12C inhibitors, which demonstrated that direct inhibition of mutant KRAS was scientifically feasible. However, these drugs benefit only a small proportion of patients with pancreatic cancer because the KRAS G12C mutation is relatively uncommon in PDAC. The majority of patients instead harbor other mutations, such as KRAS G12D, G12V, or G12R, for which effective targeted therapies have remained unavailable until recently. (随着 KRAS G12C 抑制剂 的成功研发，科学界首次证明了直接靶向 KRAS 突变蛋白是可行的。然而，由于 KRAS G12C 突变在胰腺癌中的发生率仅约 1%–2%，因此真正能够从这类药物中获益的患者数量十分有限。相比之下，大多数 PDAC 患者携带的是 KRAS G12D、G12V 或 G12R 等其他突变，而针对这些突变的有效靶向治疗长期以来一直缺乏，这也成为胰腺癌精准治疗面临的重要挑战。)

What Makes RMC-6236 Different? (RMC-6236 有何不同？)

Daraxonrasib (RMC-6236) represents a new generation of targeted therapy known as a pan-RAS(ON) inhibitor. Rather than focusing on a single KRAS mutation, RMC-6236 is designed to inhibit multiple activated forms of KRAS, NRAS, and HRAS, thereby expanding the number of patients who may potentially benefit from targeted treatment. (Daraxonrasib（RMC-6236） 属于新一代靶向治疗药物，被称为 泛 RAS（ON）抑制剂（Pan-RAS(ON) Inhibitor）。与仅针对单一 KRAS 突变的药物不同，RMC-6236 能够同时抑制多种处于活化状态的 KRAS、NRAS 和 HRAS 突变体，因此理论上可覆盖更广泛的 RAS 驱动型肿瘤患者。)

Instead of targeting only one specific mutation, RMC-6236 recognizes a structural feature shared by multiple activated RAS proteins. By binding to activated RAS together with the intracellular protein cyclophilin A, it forms a stable molecular complex that prevents RAS from transmitting growth-promoting signals to downstream pathways. As a result, cancer cells lose one of their most important mechanisms for uncontrolled growth and survival. (RMC-6236 并非只针对某一种 KRAS 突变，而是识别多种活化 RAS 蛋白共同具有的结构特征。药物通过与活化状态的 RAS 蛋白及细胞内蛋白 Cyclophilin A（亲环蛋白 A） 结合，形成稳定的三元复合物，从而阻断 RAS 向下游信号通路传递促进肿瘤生长的信号，使癌细胞失去持续增殖和存活的重要驱动力。)

This broader mechanism is particularly important for pancreatic cancer because the overwhelming majority of patients carry KRAS mutations other than G12C. Consequently, RMC-6236 has the potential to treat a substantially larger patient population than currently available mutation-specific KRAS inhibitors. (这一作用机制对于胰腺癌尤为重要，因为绝大多数患者携带的并非 KRAS G12C，而是其他 KRAS 突变类型。因此，与现有仅针对 KRAS G12C 的靶向药相比，RMC-6236 有望惠及更多胰腺癌患者，显著扩大精准治疗的适用人群。)

Another important distinction is that RMC-6236 targets the active ("ON") state of RAS proteins. Since cancer-causing KRAS mutations keep the protein continuously activated, inhibiting this active state directly addresses the biological mechanism responsible for tumor progression. This innovative approach reflects a major shift in cancer drug development—from targeting individual mutations to targeting a common mechanism shared by multiple RAS-driven cancers. (RMC-6236 的另一项重要创新在于，它靶向的是 RAS 蛋白的活化（ON）状态。由于致癌性 KRAS 突变会使 RAS 长期保持激活状态，因此直接抑制这一活化构象能够更精准地切断驱动肿瘤发展的核心机制。这标志着肿瘤靶向治疗理念的重要转变——从针对单一基因突变，发展到针对多种 RAS 驱动肿瘤共同依赖的致癌机制。)

Unlike conventional chemotherapy, which attacks rapidly dividing cells regardless of whether they are cancerous or healthy, RMC-6236 is designed to selectively interfere with abnormal molecular signaling inside cancer cells. This precision-based approach aims to maximize antitumor activity while maintaining a manageable safety profile, an important goal in modern precision oncology. (与传统化疗在杀伤癌细胞的同时也会影响正常快速分裂细胞不同，RMC-6236 主要针对癌细胞异常激活的分子信号通路进行精准干预。这种精准治疗策略旨在提高抗肿瘤疗效，同时尽可能降低对正常组织的影响，体现了现代精准肿瘤治疗的发展方向。)

Although RMC-6236 remains an investigational medicine and has not yet become standard therapy in most countries, its novel mechanism of action and encouraging early clinical results have positioned it among the most closely watched emerging therapies in pancreatic cancer research. (尽管 RMC-6236 目前仍处于临床研究阶段，尚未在大多数国家成为标准治疗方案，但凭借其创新的作用机制以及令人鼓舞的临床研究结果，它已成为全球胰腺癌精准治疗领域最受关注的新型靶向药物之一。)

Encouraging Clinical Trial Results (令人鼓舞的临床试验结果)

The growing optimism surrounding Daraxonrasib (RMC-6236) is based not only on promising laboratory research but, more importantly, on encouraging results from clinical trials involving patients with advanced RAS-mutated cancers. These studies have provided the first evidence that broad inhibition of activated RAS proteins can produce meaningful clinical benefits in cancers that have historically been among the most difficult to treat. (人们对 Daraxonrasib（RMC-6236） 日益增长的信心，不仅来自实验室研究取得的积极成果，更重要的是来自晚期 RAS 突变肿瘤 患者临床试验所获得的令人鼓舞的数据。这些研究首次证明，广泛抑制活化状态的 RAS 蛋白，有望为长期以来治疗困难的恶性肿瘤带来切实的临床获益。)

In the ongoing first-in-human Phase I/II clinical trial (ClinicalTrials.gov Identifier: NCT05379985), RMC-6236 has demonstrated encouraging antitumor activity in patients with previously treated advanced solid tumors harboring RAS mutations. Among patients with metastatic pancreatic cancer, investigators observed meaningful tumor shrinkage, durable disease control, and encouraging survival outcomes. Importantly, many participants had already received standard chemotherapy before enrolling in the study, highlighting the potential value of RMC-6236 even in heavily pretreated disease. (在正在进行的**首次人体 I/II 期临床试验（ClinicalTrials.gov 注册号：NCT05379985）**中，RMC-6236 在既往接受过治疗的晚期 RAS 突变实体瘤 患者中表现出令人鼓舞的抗肿瘤活性。在转移性胰腺癌患者中，研究人员观察到肿瘤明显缩小、疾病得到持续控制，并显示出积极的生存趋势。值得注意的是，许多受试者在入组前已经接受过标准化疗，这进一步说明 RMC-6236 即使在经过多线治疗后的患者中，仍具有潜在的治疗价值。)

More recently, the international Phase III RASolute-302 trial (ClinicalTrials.gov Identifier: NCT06625320) compared RMC-6236 with standard second-line chemotherapy in patients with previously treated metastatic pancreatic ductal adenocarcinoma carrying KRAS G12 mutations. The study demonstrated significant improvements in overall survival (OS) and progression-free survival (PFS) among patients receiving RMC-6236 compared with those receiving conventional chemotherapy. These findings represent a major milestone because they provide the first high-level randomized evidence that pan-RAS inhibition can improve survival in patients with advanced pancreatic cancer. (近期完成的国际多中心 III 期 RASolute-302 临床试验（ClinicalTrials.gov 注册号：NCT06625320），将 RMC-6236 与标准二线化疗进行了比较，研究对象为既往接受过治疗且携带 KRAS G12 突变 的转移性胰腺导管腺癌患者。研究结果显示，接受 RMC-6236 治疗的患者在总生存期（Overall Survival，OS） 和**无进展生存期（Progression-Free Survival，PFS）**方面均优于接受传统化疗的患者。这一研究具有里程碑意义，因为它首次通过随机 III 期临床试验证实，泛 RAS 抑制策略能够改善晚期胰腺癌患者的生存获益。)

Equally encouraging, the safety profile observed in clinical studies has generally been manageable. Most treatment-related adverse events have been mild to moderate in severity and could be managed with supportive care, dose interruption, or dose adjustment. Although continued long-term follow-up is essential, these findings suggest that RMC-6236 may offer an effective treatment option while maintaining an acceptable balance between efficacy and tolerability. (同样令人欣慰的是，临床研究显示 RMC-6236 总体具有可管理的安全性。大多数治疗相关不良反应属于轻度或中度，可通过支持治疗、短暂停药或调整剂量得到有效控制。尽管仍需更长期的随访来进一步评估其安全性和长期疗效，但现有证据表明，RMC-6236 有望在提高治疗效果的同时，保持较好的耐受性。)

Although regulatory authorities in many countries are still reviewing the available evidence, the results reported thus far have generated considerable enthusiasm within the international oncology community. Many experts believe that pan-RAS inhibitors may soon become an important addition to the treatment landscape for patients with KRAS-mutated pancreatic cancer. (尽管许多国家和地区的药品监管机构仍在对现有临床证据进行审评，但目前公布的研究结果已在国际肿瘤学界引起广泛关注。许多专家认为，泛 RAS 抑制剂有望在不久的将来成为 KRAS 突变胰腺癌 精准治疗的重要组成部分。)

Beyond Pancreatic Cancer (不仅限于胰腺癌)

The significance of RMC-6236 extends well beyond pancreatic cancer. Alterations in the RAS signaling pathway are among the most common genetic abnormalities in human cancer, occurring in approximately one-third of all malignancies. As a result, therapies capable of targeting multiple activated RAS variants have the potential to benefit patients across a broad spectrum of tumor types. (RMC-6236 的意义不仅局限于胰腺癌。RAS 信号通路异常是人类肿瘤中最常见的分子改变之一，大约三分之一的恶性肿瘤存在不同形式的 RAS 突变。因此，能够同时抑制多种活化 RAS 蛋白的新型药物，有望为更多类型的肿瘤患者带来新的治疗机会。)

Researchers are currently evaluating RMC-6236 in several RAS-driven cancers, including non-small cell lung cancer (NSCLC), colorectal cancer (CRC), and other advanced solid tumors. Because the drug is designed to inhibit multiple activated KRAS, NRAS, and HRAS variants rather than a single mutation subtype, it may be applicable to a much larger patient population than earlier mutation-specific targeted therapies. (目前，研究人员正在多种 RAS 驱动型肿瘤 中评估 RMC-6236 的疗效，包括非小细胞肺癌（NSCLC）、**结直肠癌（CRC）**以及其他晚期实体瘤。由于 RMC-6236 能够同时抑制多种活化的 KRAS、NRAS 和 HRAS 突变，而不仅限于某一种特定突变，因此其潜在适用人群远大于以往针对单一 KRAS 突变开发的靶向药物。)

Beyond its use as a single agent, RMC-6236 is also being investigated in combination with chemotherapy, immunotherapy, and other targeted therapies. Combination strategies may further enhance treatment efficacy by simultaneously blocking multiple mechanisms that cancer cells use to survive and develop resistance. Whether these approaches can translate into longer survival and improved quality of life remains an important focus of ongoing clinical research. (除了单药治疗之外，RMC-6236 还正在与化疗、免疫治疗以及其他靶向治疗联合开展临床研究。联合治疗有望通过同时阻断肿瘤细胞赖以生存和产生耐药性的多种机制，进一步提高治疗效果。这些联合策略能否延长患者生存时间、改善生活质量，仍是当前临床研究的重要方向。)

The development of pan-RAS inhibitors also carries broader scientific significance. For decades, many researchers believed that effective inhibition of RAS would be impossible. The clinical progress achieved with RMC-6236 demonstrates how advances in structural biology, medicinal chemistry, and precision oncology can transform previously "undruggable" targets into realistic therapeutic opportunities. (泛 RAS 抑制剂的发展还具有更深远的科学意义。几十年来，许多研究人员曾认为 RAS 几乎不可能被成功靶向。然而，RMC-6236 的临床进展充分展示了结构生物学、药物化学以及精准肿瘤学的发展如何将曾经被认为“不可成药”的靶点逐步转变为具有现实临床价值的治疗策略。)

If ongoing studies continue to confirm its efficacy and safety across different tumor types, RMC-6236 could become more than a promising treatment for pancreatic cancer. It may represent the beginning of a new era in the management of RAS-driven cancers, offering hope to a much broader population of patients facing some of the most challenging malignancies in oncology. (如果未来的临床研究能够持续证实其在不同肿瘤中的疗效与安全性，那么 RMC-6236 的意义将不仅仅局限于胰腺癌治疗。它有望开启 RAS 驱动型肿瘤 精准治疗的新篇章，为更多面临复杂恶性肿瘤挑战的患者带来新的希望。)

What Should Patients Know? (患者需要了解什么？)

Despite the encouraging clinical results, it is important to recognize that Daraxonrasib (RMC-6236) is still an investigational medicine in many countries and regions. While the recent Phase III clinical trial results are highly promising, regulatory review and approval processes are still ongoing in many jurisdictions. Until formal approval is granted, access to the drug may be limited to participation in approved clinical trials or other regulatory pathways. (尽管目前公布的临床研究结果令人鼓舞，但需要强调的是，Daraxonrasib（RMC-6236） 在许多国家和地区仍属于临床研究阶段药物。虽然最新的 III 期临床试验结果显示出良好的疗效前景，但相关监管机构仍在进行审评。在正式获得上市批准之前，患者通常只能通过获批的临床试验或其他特殊监管途径获得该药物。)

Not every patient with pancreatic cancer is an appropriate candidate for RMC-6236. Because the drug specifically targets cancers driven by activated RAS proteins, molecular testing is essential to determine whether a patient's tumor carries an eligible KRAS or other RAS mutation. Precision medicine begins with accurate diagnosis, and comprehensive genomic testing has become an increasingly important component of modern cancer care. (并非所有胰腺癌患者都适合接受 RMC-6236 治疗。由于该药物主要针对由活化 RAS 蛋白驱动的肿瘤，因此进行**分子检测（基因检测）**对于确定患者是否携带符合治疗条件的 KRAS 或其他 RAS 突变至关重要。精准医疗始于精准诊断，全面的基因检测已成为现代肿瘤诊疗的重要组成部分。)

Patients and their families should discuss all available treatment options with their oncology team. Factors such as the stage of disease, previous treatments, overall health status, genetic test results, and individual treatment goals all play important roles in selecting the most appropriate therapy. No single treatment is suitable for every patient, and personalized treatment planning remains the cornerstone of high-quality cancer care. (患者及其家属应与肿瘤专科医生充分沟通，全面了解各种治疗方案。疾病分期、既往治疗情况、整体健康状况、基因检测结果以及个人治疗目标等因素，都会影响最终治疗方案的选择。没有一种治疗方法适用于所有患者，制定个体化治疗方案始终是高质量肿瘤医疗的核心原则。)

It is equally important for patients to maintain realistic expectations. Although RMC-6236 has demonstrated encouraging clinical activity, no targeted therapy can currently guarantee a cure for advanced pancreatic cancer. Continued clinical research, long-term follow-up, and further improvements in treatment strategies will be essential to maximize patient benefit. (与此同时，患者也应保持理性而积极的期望。虽然 RMC-6236 已展现出令人鼓舞的临床疗效，但目前尚无任何靶向治疗能够保证治愈晚期胰腺癌。未来仍需要更多临床研究、更长期的随访以及不断优化治疗策略，以进一步提高患者的长期获益。)

Nevertheless, every major advance in cancer treatment has begun with carefully conducted clinical research. The progress achieved with RMC-6236 reflects decades of scientific dedication and offers renewed optimism for patients who previously had very limited treatment options. (然而，几乎所有癌症治疗的重要突破，都源于严谨而持续的临床研究。RMC-6236 所取得的进展凝聚了科研人员数十年的努力，也为过去治疗选择十分有限的胰腺癌患者重新点燃了希望。)

Looking Ahead (展望未来)

For many years, pancreatic cancer has been associated with limited therapeutic progress and poor clinical outcomes. The emergence of Daraxonrasib (RMC-6236) suggests that this long-standing narrative may finally be beginning to change. By targeting one of the most fundamental drivers of pancreatic cancer, this innovative therapy has demonstrated that even the most challenging molecular targets can eventually become druggable through scientific innovation. (长期以来，胰腺癌一直被认为是治疗进展缓慢、预后极差的恶性肿瘤之一。Daraxonrasib（RMC-6236） 的出现，预示着这一局面或许正在发生改变。通过精准靶向胰腺癌最核心的致癌驱动因素之一，该药物证明，即使曾被认为“不可成药”的分子靶点，也有可能随着科学技术的发展而实现突破。)

The journey, however, is far from complete. Researchers continue to investigate how RMC-6236 can be integrated into earlier stages of treatment, whether it can be combined effectively with chemotherapy, immunotherapy, or other targeted therapies, and how resistance to treatment can be delayed or overcome. Answers to these questions will shape the next generation of precision oncology. (然而，这项探索仍远未结束。研究人员正在积极探索 RMC-6236 是否能够应用于疾病更早期阶段，是否能够与化疗、免疫治疗或其他靶向治疗联合使用，以及如何延缓或克服耐药性的发生。这些问题的答案，将决定下一代精准肿瘤治疗的发展方向。)

For healthcare professionals, RMC-6236 represents an exciting example of how advances in molecular biology, medicinal chemistry, and translational research can rapidly translate into meaningful clinical benefits. For researchers, it validates decades of effort devoted to understanding and targeting the RAS signaling pathway. (对于医务人员而言，RMC-6236 展示了分子生物学、药物化学以及转化医学如何共同推动创新成果快速走向临床，为患者带来切实获益。对于科研工作者来说，它进一步证明了数十年来针对 RAS 信号通路 的持续研究是值得的。)

Most importantly, for patients and their families, RMC-6236 represents more than a promising new medicine. It symbolizes scientific progress, renewed possibilities, and the hope that future generations of patients diagnosed with pancreatic cancer may have access to safer, more effective, and more personalized treatment options than ever before. (更重要的是，对于患者及其家属而言，RMC-6236 不仅仅是一种具有前景的新药，更象征着科学不断进步所带来的新希望。它意味着未来的胰腺癌患者有望获得更加安全、更加有效、更加精准的个体化治疗，从而拥有更长的生存时间和更好的生活质量。)

While additional evidence and longer follow-up are still needed, the progress achieved thus far suggests that the era of precision medicine for KRAS-mutated pancreatic cancer has truly begun. The story of RMC-6236 is still being written, but it already stands as one of the most encouraging chapters in modern pancreatic cancer research. (尽管仍需要更多研究证据和更长期的随访数据来进一步验证其价值，但目前取得的成果已经表明，KRAS 突变胰腺癌精准治疗时代正在逐步开启。RMC-6236 的故事仍在继续书写，而它已经成为现代胰腺癌研究中最令人振奋的篇章之一。)

Selected References 参考文献（精选）

1. O'Reilly EM, Wolpin BM, et al. Daraxonrasib or Chemotherapy in Previously Treated Metastatic Pancreatic Ductal Adenocarcinoma. New England Journal of Medicine. 2026.

2. ClinicalTrials.gov. NCT05379985. A Study of RMC-6236 in Patients with Advanced Solid Tumors Harboring Specific Mutations in RAS.

3. ClinicalTrials.gov. NCT06625320. RASolute-302: A Phase III Study of Daraxonrasib (RMC-6236) versus Standard Therapy in Previously Treated Metastatic Pancreatic Ductal Adenocarcinoma.

4. Moore AR, Rosenberg SC, McCormick F, Malek S. RAS-Targeted Therapies: Is the Undruggable Drugged? Nature Reviews Drug Discovery. 2020;19:533–552.

5. Simanshu DK, Nissley DV, McCormick F. RAS Proteins and Their Regulators in Human Disease. Cell. 2017;170(1):17–33.

6. Cox AD, Fesik SW, Kimmelman AC, Luo J, Der CJ. Drugging the Undruggable RAS: Mission Possible? Nature Reviews Drug Discovery. 2014;13(11):828–851.

7. Waters AM, Der CJ. KRAS: The Critical Driver and Therapeutic Target for Pancreatic Cancer. Cold Spring Harbor Perspectives in Medicine. 2018;8:a031435.

8. Ryan MB, Corcoran RB. Therapeutic Strategies to Target RAS-Mutant Cancers. Nature Reviews Clinical Oncology. 2018;15:709–720.