人類處方藥物｜突破性癌症療法：百靈佳殷格翰的創新之路　Taking cancer care personally can make a world of difference

對多數人來說，在生命中的某個階段會經歷到摯愛的人與癌症抗爭，或者自己罹患癌症。這些親身經歷觸動了百靈佳殷格翰的研究人員，並成為他們決心投入腫瘤學和癌症治療的初衷。

「幾乎每個人多少都會受到癌症的影響。這使得研究癌症治療對我們來說不僅僅是一份工作，它激發了我們的決心與靈感，讓我們齊心投入能改變生活的科學研究。」

Norbert Kraut, 百靈佳殷格翰全球癌症研究中心負責人（Global Head of Cancer Research at Boehringer Ingelheim）

團隊們決定投入腫瘤學領域中一系列尚未被滿足的治療需求。Kruat 相信，百靈佳殷格翰的員工和文化非常適合探索針對特定類型癌症的解決方案，以及打造符合癌症患者個人需求的治療方案。

「百靈佳殷格翰的獨立結構讓我們得以支撐患者的需求，敢於承諾並提供長期的陪伴…同時也能滿足我們身為科學家的好奇心並遵循科學。我相信，這兩者結合起來激發了創新的火花。」

Norbert Kraut, 百靈佳殷格翰全球癌症研究中心負責人（Global Head of Cancer Research at Boehringer Ingelheim）

以創新力締造穩健的醫療進程

百靈佳殷格翰的科學家們在好奇心的驅使之下，開發了一個強大的腫瘤學治療進程，涵蓋多種作用機制。

例如， T 細胞銜接抗體（T-cell engagers）藉由將自身附著到癌細胞的特定蛋白質上，引導免疫系統檢測和攻擊腫瘤。在一項正在進行的臨床研究中，一種名為 BI 764532 的新型 T 細胞銜接抗體展示了極大的潛能，能作為對抗靶向 DLL3 蛋白質（delta-like ligand 3）的癌細胞（像是小細胞肺癌和其他轉移性神經內分泌腫瘤）的方法之一。

近期在精準腫瘤學領域也有新突破，針對癌細胞的關鍵驅動因子與特徵，研擬直接殺死癌細胞的方法。

百靈佳殷格翰應用精準腫瘤學研究而研發出的另一種藥物是具備高度選擇性且強效的小分子抑制劑，可與 HER2（第2型人類上皮生長因子受器）結合。HER2 基因是一種重要及潛在的致癌基因，有可能突變為非小細胞肺癌（NSCLC，non-small-cell lung cancer），每年約有 40,000 人被診斷為患有此疾病。

攜手改變癌症照護

這些進步都不是個人單打獨鬥的成就，而是與其他科學家和組織合作的結果。癌症帶來的複雜挑戰，需要多元化的思維與專業知識，因此百靈佳殷格翰建立強大的研究合作夥伴網絡。

合作網絡的成員共同透過藥物探索與數據分析等創新技術，擴大他們從癌症模型中進行大規模功能性篩選研究獲取資訊的能力，對來自臨床和生物銀行的匿名數據提出進一步見解。

運用最新的電腦技術，將能夠建立統整所有的癌症驅動因子和其他關鍵癌症依賴性因素的目錄。還可以精確定位生物標記（biomarkers），幫助識別與患者最適合的特定化合物。生物標記也能協助判斷劑量、解釋作用機制、引導潛在藥物組合、理解抗藥性機制並為下一代治療方案提供資訊。

百靈佳殷格翰最具有遠大抱負的研究項目之一是與紀念斯隆凱特琳癌症中心（Memorial Sloan Kettering Cancer Center）合作，研究突變率最高的致癌基因KRAS。KRAS 的縮寫源自鼠肉瘤病毒（Kirsten），Kirsten rat sarcoma virus。KRAS 與胰臟癌、非小細胞肺癌（NSCLC）、結直腸癌等高度致死癌症相關。2023 年 5 月，我們在《自然Nature》雜誌發表了一篇關於標靶治療的文章，經過了四十年，科學家在征服 KRAS 這個「癌症基因的聖母峰」的漫長道路上終於成功邁出了一步。¹

百靈佳殷格翰與夥伴之間的合作關係旨在齊心面對健康公平和患者取得的挑戰。隨著更多新型療法不斷出現，確保全球病患都有機會接觸新療法，並且取得相關資訊至關重要。百靈佳殷格翰正在與軟組織腫瘤患者全球行動網（SPAGN）、國際抗癌聯盟（UICC）、全球肺癌聯盟（GLCC）等單位合作，協助患者了解正在對抗的疾病，以及可行的治療方案。這些努力有也助於提高對癌症早期檢測的重視程度。

能持續提供能改變生活並且優質的治療方案，是百靈佳殷格翰團隊的動力來源。我們渴望讓患者能享有更美好、長久的生活，也為他們的家人和朋友帶來希望。百靈佳殷格翰人類處方用藥負責人 Carinne Brouillon 總結了百靈佳殷格翰的使命感：「癌症為我們帶來極為複雜並且具有挑戰性的科學難題。醫學界皆致力於解開癌症這個難題，因為它對我們社區、我們所愛的人甚至我們自己有著巨大的影響。」

「我們都在同一艘船上。」

Carinne Brouillon, 百靈佳殷格翰人類處方用藥負責人（Head of Human Pharma at Boehringer Ingelheim）

Taking cancer care personally can make a world of difference

Cancer claims 10 million lives prematurely each year. Boehringer Ingelheim understands what's at stake and is committed to developing treatments that will transform cancer care. 

At some point in our lives, most of us will experience a loved one struggling with cancer ... or suffer from it ourselves. Such first-hand experiences motivate many of the researchers at Boehringer Ingelheim and underlie their dedication to oncology and cancer treatment.

“Nearly all of us have somehow been impacted by this disease. That makes this something bigger than just a job. It gives us the determination and inspiration to team up to accelerate life-changing science.”

Norbert Kraut, Global Head of Cancer Research at Boehringer Ingelheim

The team has identified a range of unmet needs in oncology, and Kraut believes that Boehringer's people and culture are uniquely suited to exploring solutions tailored to the characteristics of specific types of cancer, as well as to the individual needs of those living with cancer. 

“Our independent structure fosters a long-term commitment to the patient's greatest needs... but it also lets us live our curiosity as scientists and follow science. I believe that, together, these produce the spark that makes innovation happen.”

Norbert Kraut, Global Head of Cancer Research at Boehringer Ingelheim

Innovating to create a robust pipeline of treatments

By living their curiosity, Boehringer's scientists have developed a robust oncology pipeline that draws on a diversity of mechanisms of action.

For example, T-cell engagers harness the immune system's ability to detect and destroy tumors by attaching themselves to specific proteins expressed by cancer cells. In one ongoing clinical study, a new T-cell engager called BI 764532 shows great promise as a way to fight cancer cells that express the delta-like ligand 3 (DLL3) protein on their surface, such as small cell lung cancer and other metastatic neuroendocrine carcinomas.

Other recent breakthroughs have emerged from precision oncology, which targets key drivers and hallmarks to kill cancer cells directly.

Another drug now being developed by Boehringer that relies on precision oncology is a highly selective and potent small molecule inhibitor that binds to the HER2 protein. The gene that encodes for the HER2 protein is an important oncogene, i.e., a potential cancer causer, and alterations in the gene can turn HER2 into a cancer driver for non-small-cell lung cancer (NSCLC). The condition is diagnosed in roughly 40,000 people every year. 

Teaming up to transform cancer care

These advances have been achieved not in isolation, but in collaboration with other scientists and organizations. The complex challenges presented by cancer call for a diversity of ideas and specializations – which is why Boehringer has built up a strong network of research partners.

Together, the members of this network are leveraging innovations in drug discovery and data analytics to expand their ability to study information drawn from large-scale functional screening in cancer models. Further insights are being drawn from large quantities of anonymized data provided by clinics and biobanks.

Deploying the latest computational techniques will make it possible to build a comprehensive catalogue of cancer drivers and other key cancer dependencies. This work can also pinpoint biomarkers that may help identify patients who will benefit the most from specific compounds. Such biomarkers can also assist in dose selection, explaining mode of action, guiding potential treatment combinations, understanding resistance mechanisms and informing the next generation of treatments.

In one of its most ambitious research projects, Boehringer is working with the Memorial Sloan Kettering Cancer Center to target the oncogene with the highest mutation rate, KRAS, whose name comes from it having been initially identified in Kirsten rat sarcoma virus. KRAS is associated with highly fatal cancers such as pancreatic, NSCLC and colorectal cancer. The publication of an article in Nature in May 2023 on targeted therapy marks a step on the long path to conquering this “Everest of oncogenes,” which scientists have been pursuing for four decades now.¹

Moreover, Boehringer's partnerships seek to address challenges presented by health equity and patient access. As new treatments emerge, it is essential to ensure that patients around the globe have access to them and information about them. Boehringer is working with patient organizations such as SPAGN, UICC and GLCC to help people learn about their diseases and the available treatment options. These efforts also raise awareness about the importance of early detection.

The work of delivering life-changing, best-in-class treatments will continue to inspire the people of Boehringer. Their determination is driven not simply by a desire to help patients live better and longer lives, but by the need to give hope to their families and friends. Carinne Brouillon, Head of Human Pharma at Boehringer Ingelheim, sums up Boehringer Ingelheim's sense of mission: “Cancer presents us with an exceptionally complex and challenging scientific puzzle. The medical community is committed to solving that puzzle because of the huge impact it has on our communities, our loved ones and ourselves.”

“We are all in this together.”

Carinne Brouillon, Head of Human Pharma at Boehringer Ingelheim

¹Kim, D., Herdeis, L., Rudolph, D. et al. Pan-KRAS inhibitor disables oncogenic signalling and tumour growth. Nature 619, 160–166 (2023). https://doi.org/10.1038/s41586-023-06123-3