研發更多類似新型胰臟癌藥物的競賽

Recently The New York Times reported the following:

(Source: The NYT)

The Race to Develop More Medicines Like the New Pancreatic Cancer Drug

Companies are testing dozens of similar drugs in cancers of the pancreas, lung, colon and more.

The NYT - By Rebecca Robbins and Carolyn Y. Johnson

Aug. 27, 2026

The Food and Drug Administration’s approval on Wednesday of a new drug for pancreatic cancer marked the end of a long quest to develop a medicine that can hit one of cancer’s most elusive targets.

Researchers hope the new drug is just the beginning, opening a new chapter in treatment for a range of cancer types.

At least 79 drugs that take a similar approach are being tested in 238 clinical trials worldwide, according to one tally by academic researchers.

Large drugmakers like Eli Lilly, Pfizer, Amgen and AstraZeneca are among the companies racing to develop their own medicines that work like the new drug, daraxonrasib, which is made by Revolution Medicines and will be sold as Rasonque.

The new drug, taken as two daily pills, attacks a mutated cellular protein called KRAS. It has long been an enticing target, because it fuels nearly all pancreatic cancers, as well as many lung and colon cancers and some other tumor types. But for years, the smooth-surfaced KRAS protein was considered impossible to attack, because it lacked an obvious toehold for a drug to exploit.

But a series of scientific advances gradually overturned that doctrine, showing that KRAS could be conquered. Starting around 2024, research activity in the field exploded.

“This is not just pancreatic cancer,” said Dr. David S. Hong, an oncologist at MD Anderson Cancer Center in Houston and one of the leaders of an early safety study of daraxonrasib. He compared its landmark approval to the advent about 15 years ago of a powerful class of immunotherapy drugs, called immune checkpoint inhibitors, that are now used against a broad array of tumors.

Cancer is a slippery foe that often finds a way to evade one particular therapy, and there’s hope that treating it with multiple approaches simultaneously could help squelch tumors. Already, studies are underway that test combinations of KRAS-targeting drugs alongside other types of therapies to launch a multipronged attack. Daraxonrasib’s approval could lead to more such trials.

Researchers widely agree that the emerging class of drugs “will need combinations to advance their clinical response and durability,” said Channing Der, a pioneering KRAS scientist who oversees academic labs in North Carolina and Berlin that have been tracking experimental drugs and trials in the field.

Revolution Medicines, a small company near San Francisco that had no approved products before daraxonrasib, is widely seen as the leader in the field. One of its most closely watched, and potentially most significant, trials is testing daraxonrasib as the first drug given after a pancreatic cancer diagnosis, instead of as a second-line treatment for people who had already tried chemotherapy, the group for which the drug won approval.

Revolution is also developing a similar medicine, zoldonrasib, that has shown early promise for lung cancer. The company also has collaborations underway with drugmakers like Bristol Myers Squibb, Tango Therapeutics and Summit Therapeutics to study combinations involving its KRAS-targeting drugs.

Daraxonrasib is not the first to target KRAS. Two others, sold by Amgen and Bristol Myers Squibb, won approval to treat forms of lung cancer several years ago. But those drugs were disappointments. They delivered only modest benefits, because they targeted only one mutant form of KRAS, and only when it was not actively driving cancer growth. As a result, tumors rapidly mutated to evade the treatment.

Drugs like daraxonrasib and others in development are more powerful because they can work on an array of mutations, and because they block KRAS when it is actively causing cancer growth. But they run into the same problem as other targeted therapies; eventually, the treatment stops working and the cancer returns.

KRAS is part of a family of proteins that develop mutations in about a fifth of human cancers, including some that have not historically been thought to be susceptible to this kind of treatment approach.

Take breast cancer, for example. KRAS mutations are very rare in breast tumors, but when the breast cancer spreads to other parts of the body, like the lungs or the liver, and develops a resistance to treatment, it can sometimes develop KRAS mutations.

Researchers now hope to plan a clinical trial that would test the approach in breast cancer, said Ariella Hanker of the Simmons Comprehensive Cancer Center at UT Southwestern Medical Center, one of the scientists involved in the work.

Dr. Elizabeth Jaffee, a pancreatic cancer researcher at Johns Hopkins, listed some of the most pressing needs in the field: Creating a new generation of KRAS-targeting drugs with fewer side effects; finding ways to overcome the resistance that allows cancer to surge back; and combining KRAS-targeting drugs with other treatments, including those that harness a patient’s immune system to attack cancer.

“We’re all really excited, of course,” she said. But, she added, “we have a lot to do.”

Achieving those goals will require close collaboration between companies with competing interests, she said. And in one case, tensions have already crept into public view.

One drugmaker, Erasca, has generated attention for early-stage studies of its KRAS-targeting drug, ERAS-0015, in cancers of the lung and pancreas. That experimental drug is similar to daraxonrasib — so similar, in fact, that, in a letter last spring, Revolution Medicines’s lawyers accused its competitor of violating a key patent, and demanded that it stop work on the drug in the United States. Erasca, which is based in San Diego and bought the rights to its experimental drug from a Chinese company, has denied the accusations.

Translation

研發更多類似新型胰臟癌藥物的競賽

各大公司正在針對胰臟癌、肺癌、結腸癌等多種癌症去測試數十種類似藥物

美國食品藥物管理局（FDA）週三批准了一種治療胰臟癌的新藥，這標誌著一項旨在攻剋癌症最難捉摸的標靶之一的藥物研發旅程終於結束。

研究人員希望這種新藥只是個開始，它將開啟多種癌症治療的新篇章。

根據學術研究人員統計，目前全球至少有79種採用類似療法的藥物正在進行238項臨床試驗。

禮來、輝瑞、安進和阿斯特捷利康等大型製藥公司都在競相研發類似 daraxonrasib 的藥物。daraxonrasib 由 Revolution Medicines 公司研發，將以 Rasonque 的商品名上市。

這種新藥每日服用兩粒，作用於一種名為 KRAS 的突變細胞蛋白。 KRAS 蛋白長期以來都是一個極受注視的目標，因為它幾乎是所有胰臟癌以及許多肺癌、結腸癌和其他一些腫瘤類型的致病因素。但多年來，人們一直認為 KRAS 蛋白表面光滑，難以攻擊，因為它缺乏藥物可以利用的明確立足點。

然而，一連串科學進展逐漸推翻了這個觀點，顯示 KRAS 是可以被攻克的。從2024年左右開始，該領域的研究活動呈現爆炸性增長。

休士頓MD安德森癌症中心的腫瘤學家、daraxonrasib早期安全性研究的負責人之一David S. Hong博士說: 「這不僅僅是胰臟癌」。他將這項劃時代的獲批准，比作大約15年前出現的一類強效免疫療法藥物，稱為免疫檢查點抑制劑，這類藥物目前被廣泛應用於對抗各種腫瘤。

癌症是個狡猾的敵人，它常常能找到辦法逃避某種特定的療法，因此人們寄望多種療法的聯合治療能夠有效抑制腫瘤。目前，一些研究正在進行中，目的在測試 KRAS 標靶藥物與其他療法合併使用的效果，以發動多管齊下的攻勢。 Daraxonrasib 的批准可能會促成更多此類試驗。

主管在北卡羅來納州以及柏林的學術實驗室的KRAS研究先驅 Channing Der 說研究人員普遍認為，這類新興藥物「需要聯合用藥才能提高其臨床療效和持久性」，這些實驗室一直在追蹤該領域的實驗性藥物和試驗。

Revolution Medicines 是一家位於舊金山附近的小型公司，在 daraxonrasib 問世之前沒有任何核准產品，如今卻被廣泛認為是該領域的領導者。該公司最受關注、也可能最具意義的試驗之一，是測試 daraxonrasib 作為胰腺癌診斷後的第一線藥物，而不是作為已經嘗試過化療的患者的二線治療，該藥物早已獲准用於這組嘗試過化療人仕。

Revolution 也正在開發一種類似的藥物 zoldonrasib，該藥物在肺癌治療方面已展現出早期療效。此外，該公司也與百時美施貴寶、Tango Therapeutics 和 Summit Therapeutics 等製藥公司合作，研究其KRAS標靶藥物的聯合療法。

Daraxonrasib並非首個KRAS標靶藥物。幾年前，安進以及百時美施貴寶分別銷售的另外兩種KRAS 標靶藥物也獲准用於治療某些類型的肺癌。但這些藥物最終令人失望。這些療法療效有限，因為它們只針對一種 KRAS 突變體，而且只有在 KRAS 不活躍地推動癌症生長時才起作用。結果，腫瘤迅速發生突變而令治療無效。

像 daraxonrasib 和其他正在研發的藥物有更強效力，因為它們可以對多種突變體有效力，並且能在KRAS活躍地驅動癌症生長時阻斷其活性。但它們也面臨著與其他標靶療法相同的問題：最終，治療會無效，癌症復發。

KRAS 屬於一個蛋白質家族，該家族的蛋白質在大約五分之一的人類癌症中發生突變，其中包括一些歷史上被認為對這種治療方法不太有效的癌症。

以乳癌為例。 KRAS 突變在乳腺腫瘤中非常罕見，但當乳癌擴散到身體其他部位（如肺部或肝臟）並對治療產生抗藥性時，有時會發生 KRAS 突變。

參與這項研究的科學家之一、德州大學西南醫學中心西蒙斯綜合癌症中心 的 Ariella Hanker 表示，研究人員現在希望計劃一項臨床試驗，以檢驗該方法在乳癌中的應用。

約翰霍普金斯大學的胰臟癌研究員 Elizabeth Jaffee 博士列舉了該領域一些最緊迫的需求：研發副作用更少的新一代 KRAS靶向藥物；找到克服抗藥性的方法，防止癌症復發；以及將 KRAS 標靶藥物與其他療法合併使用，包括利用患者自體免疫系統攻擊癌症的療法。

她說:“我們當然都非常興奮”。但她補充道，“我們還有很多工作要做。”

她表示，實現這些目標需要利益衝突的公司之間密切合作。在某些情況下，緊張關係已經公開化。

一家名為 Erasca 的製藥公司因其 KRAS 標靶藥物 ERAS-0015 在肺癌和胰腺癌早期研究中的表現而備受關注。這種實驗性藥物與 daraxonrasib 非常相似 - 事實上，兩者非常相似到以至 Revolution Medicines 在去年春天的律師在一封信中，指控其競爭對手侵犯了一項關鍵專利，並要求它停止在美國開展該藥物的研發工作。總部位於聖地牙哥的 Erasca 公司是從一家中國公司購買了其實驗性藥物的權利，該公司否認了這些指控。

So, in the US, an approval of a new drug for pancreatic cancer marks the end of a long quest to develop a medicine that can hit one of cancer’s most elusive targets. The new drug, taken as two daily pills, attacks a mutated cellular protein called KRAS. It has long been an enticing target, because it fuels nearly all pancreatic cancers, as well as many lung and colon cancers and some other tumor types. Researchers hope the new drug is just the beginning, opening a new chapter in treatment for a range of cancer types. Apparently, this new drug will give hope to many pancreatic cancer patients.