圖1. 美國冷泉港實驗室(CSHL)的科學家們發現了第一個致癌基因，並完成了單一腫瘤內多個個體癌細胞的第一個基因體圖譜。此些是癌腫遺傳學史上，最大的兩項突破。這已經為更有效的癌腫藥物及精確的治療策略開了路。圖上也呈現的是，CSHL導致此些發現的遺傳學家，Michael Wigler教授(右上)及W. Richard McCombie教授(右下)。
Cold Spring Harbor Laboratory scientists identified the first cancer-causing gene and completed the first genomic profile of multiple individual cancer cells within a single tumor. These breakthroughs—two of the biggest in cancer genetics history—have made way for more effective cancer drugs and precise treatment strategies. Pictured above are the CSHL geneticists responsible for these discoveries, Professor Michael Wigler (top right) and Professor W. Richard McCombie (bottom right).
What is cancer? How does it develop and spread? And how do we stop it? Thanks to science, today’s doctors can better answer all of these questions. That’s not because of one eureka moment. Instead, it’s the result of thousands of discoveries that built upon each other. Case in point: two of the most important breakthroughs in the history of cancer genetics took place at Cold Spring Harbor Laboratory (CSHL).
什麼是癌腫？其如何發生與擴散？及如何防止？由於科學，當今的醫生們能更好地回答所有此些問題。不過，這是以相互為基礎之數以千計的發現結果。切題的實例：癌腫遺傳學史上，發生於美國冷泉港實驗室(CSHL)最重要的兩項突破。
The first occurred in the early 1980s when CSHL Professor Michael Wigler and his team helped to identify the first cancer-causing gene (or oncogene) ever found in humans. Wigler’s team showed that a single amino acid change could prompt a normal cell to go rogue, leading to cancer. And this was just the start.
第項發生於20世紀80年代初，當時CSHL教授Michael Wigler及其團隊協助確認了，於人類中，曾被發現的第一個致癌基因(也就是癌腫基因)。Wigler的團隊證實了，單一胺基酸改變可能促使正常細胞變成惡棍，而引發癌腫。 然而，這只是開始。
“We found a whole family of genes that encode very similar proteins,” Wigler says. “All of them could possibly be mutated and help drive a normal cell to turn cancerous.” The discovery also confirmed that cancer isn’t always the result of genetically inherited risk.
Wigler宣稱：「我們發現了，一整群為非常相似之蛋白質編碼的基因。所有這些皆可能發生突變，而協助驅動正常細胞發生癌變。」此發現也證實，癌腫並非總是遺傳上承襲的風險結果。
Another big break came in 2011. This was the year that CSHL Professor W. Richard McCombie, along with Wigler and others, completed the first-ever genomic profile of multiple individual cancer cells within a single tumor.
另一項重大突破出現於2011年。這是CSHL教授W. Richard McCombie與 Wigler等人，有史以來首次完成，於單一腫瘤內，多個體癌細胞之基因體圖譜的年份。
The revelation showed that even in the same tumor from the same person, not every cell is the same. It also proved that tumors can evolve over time. This discovery helped explain why drugs that were once effective for treating a patient will sometimes stop working in the middle of that patient’s treatment regimen.
此揭露顯示，即使來自相同人的相同腫瘤，並非每一細胞皆相同。這也證實，腫瘤會隨著時間推移進行演化。此發現有助於解釋，為什麼曾經對治療患者有效的藥物，有時會在患者治療的療程中途失效。
圖2. 來自2011年，冷泉港實驗室W. Richard McCombie教授，顯示正常(N)及腫瘤(T)細胞百分比，說明了每一樣本遺傳多樣性之突破性成果的組織切片。
Tissue sections from CSHL Profesor W. Richard McCombie’s 2011 breakthrough. Note the normal (N) and tumor (T) cell percentages, which speak to the genetic diversity of each sample.
“It gave us a more detailed appreciation for what a tumor was,” explains McCombie. “You might take a piece of tumor or biopsy and see that a certain drug might work on it, but it won’t work on all the cells in that tumor. Maybe they’re already resistant, or they’ve evolved as the tumor evolved.”
McCombie解釋：「這使我們更詳盡的正確認知，腫瘤是什麼。人們可以取一塊腫瘤，也就是活組織切片檢查，而發現某種藥物能對其起作用，不過不會對那腫瘤中，所有細胞起作用。或許它們已經具有抵抗力，或它們已經隨著腫瘤演化，進行演化了。」
The reverberations of these breakthroughs are still being felt today. New inhibitor drugs that halt the mechanisms by which cancer grows are now being developed based on Wigler’s initial findings. These drugs seek out and bind to cancerous cells in order to stop their growth. And they do so while leaving healthy cells alone.
時至今日，人們仍感受到此些突破的回響。藉以遏阻癌腫生長機制的新藥物抑制劑，目前正根據Wigler的初步發現研發中。為了阻止癌細胞生長，此些藥物尋找出並結合它們。也就是，此些抑制劑這麼做的同時，也沒有影響健康的細胞。
Additionally, the observation that all tumor cells are not one and the same has been a key driver for the burgeoning field of precision medicine. This approach seeks to target the specific tumors a person has, with the understanding that the treatment may need to change over time. Once thought of as the next frontier in cancer care, precision medicine is now well within reach for doctors and patients across the globe.
此外，該所有腫瘤細胞並非完全相同的觀察知識，一直是精準醫學領域，蓬勃發展的關鍵驅動力。此方法尋找鎖定一人具有的特定腫瘤，儘管瞭解治療方法，可能需要隨著時間推移而改變。在癌症護理上，精準醫療曾經被認為是下一個前沿領域。目前，對全球的各地的醫生及患者而言，頗為觸手可及。
網址：https://www.cshl.edu/from-cancer-genetics-to-cancer-treatments/
翻譯：許東榮
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