How does chemotherapy work Hyunsoo Joshua No

During World War I, one of the
horrors of trench warfare

was a poisonous yellow cloud
called mustard gas.

For those unlucky enough to be exposed,

it made the air impossible to breathe,
burned their eyes,

and caused huge blisters on exposed skin.

Scientists tried desperately to develop an
antidote to this vicious weapon of war.

In the process they discovered the gas
was irrevocably damaging the bone marrow

of affected soldiers— halting its
ability to make blood cells.

Despite these awful effects,
it gave scientists an idea.

Cancer cells share a characteristic with
bone marrow: both replicate rapidly.

So could one of the atrocities of war

become a champion in the
fight against cancer?

Researchers in the 1930s
investigated this idea

by injecting compounds derived
from mustard gas

into the veins of cancer patients.

It took time and trial and error to find
treatments that did more good than harm,

but by the end of World War II,

they discovered what became known
as the first chemotherapy drugs.

Today, there are more than 100.

Chemotherapy drugs are delivered
through pills and injections

and use “cytotoxic agents,” which means
compounds that are toxic to living cells.

Essentially, these medicines cause some
level of harm to all cells in the body—

even healthy ones.

But they reserve their most powerful
effects for rapidly-dividing cells,

which is precisely the hallmark of cancer.

Take, for example, those first
chemotherapy drugs,

which are still used today and
are called alkylating agents.

They’re injected into the bloodstream,

which delivers them to
cells all over the body.

Once inside, when the cell exposes
its DNA in order to copy it,

they damage the building blocks of
DNA’s double helix structure,

which can lead to cell death unless
the damage is repaired.

Because cancer cells multiply rapidly,

they take in a high concentration
of alkylating agents,

and their DNA is frequently exposed
and rarely repaired.

So they die off more often
than most other cells,

which have time to fix damaged DNA

and don’t accumulate the same
concentrations of alkylating agents.

Another form of chemotherapy involves
compounds called microtubule stabilizers.

Cells have small tubes that assemble
to help with cell division

and DNA replication, then break back down.

When microtubule stabilizers
get inside a cell,

they keep those tiny tubes
from disassembling.

That prevents the cell from completing
its replication, leading to its death.

These are just two examples of the six
classes of chemotherapy drugs

we use to treat cancer today.

But despite its huge benefits,
chemotherapy has one big disadvantage:

it affects other healthy cells in the body
that naturally have to renew rapidly.

Hair follicles, the cells of the mouth,
the gastrointestinal lining,

the reproductive system, and bone marrow
are hit nearly as hard as cancer.

Similar to cancer cells, the rapid
production of these normal cells

means that they’re reaching for
resources more frequently—

and are therefore more exposed to
the effects of chemo drugs.

That leads to several common side
effects of chemotherapy,

including hair loss, fatigue, infertility,
nausea, and vomiting.

Doctors commonly prescribe options
to help manage these side-effects,

such as strong anti-nausea medications.

For hair loss, devices called cold caps
can help lower the temperature

around the head and
constrict blood vessels,

limiting the amount of chemotherapy
drugs that reach hair follicles.

And once a course of chemo
treatment is over,

the healthy tissues that’ve been badly
affected by the drug will recover

and begin to renew as usual.

In 2018 alone, over 17 million people
world-wide received a cancer diagnosis.

But chemotherapy and other treatments
have changed the outlook for so many.

Just take the fact that up to 95% of
individuals with testicular cancer

survive it, thanks to advances
in treatment.

Even in people with acute myeloid
leukemia— an aggressive blood cancer—

chemotherapy puts an estimated
60% of patients under 60

into remission following their
first phase of treatment.

Researchers are still developing
more precise interventions

that only target the intended
cancer cells.

That’ll help improve survival rates
while leaving healthy tissues

with reduced harm,

making one of the best tools we have
in the fight against cancer even better.

第一次世界大战期间,
堑壕战的恐怖之一

是一种叫做芥子气的有毒黄色云

对于那些不幸暴露在外的人来说,

它使空气无法呼吸,
灼伤他们的眼睛,

并在暴露的皮肤上造成巨大的水泡。

科学家们拼命地试图开发一种
解毒剂来对付这种邪恶的战争武器。

在此过程中,他们发现这种
气体不可逆转地损害了

受影响士兵的骨髓——阻止了其
制造血细胞的能力。

尽管有这些可怕的影响,
但它给了科学家们一个想法。

癌细胞与骨髓有一个共同特点
:两者都快速复制。

那么战争的暴行之一能否

成为
抗击癌症的冠军?

1930 年代的研究人员

通过将源自芥子气的化合物

注入癌症患者的静脉来研究这一想法。

找到利大于弊的治疗方法需要时间和反复试验

但到二战结束时,

他们发现了被
称为第一个化疗药物的药物。

今天,有100多种。

化疗药物
通过药丸和注射

剂输送,并使用“细胞毒剂”,
即对活细胞有毒的化合物。

从本质上讲,这些药物会对
身体的所有细胞——甚至是健康的细胞——造成一定程度的伤害

但它们将最强大的
作用保留给快速分裂的细胞,

而这正是癌症的标志。

以那些今天仍在使用的第一批
化疗药物为例,

它们被称为烷化剂。

它们被注射到血液中,血液

将它们输送
到全身的细胞中。

一旦进入内部,当细胞
为了复制它而暴露其 DNA 时,

它们会破坏
DNA 双螺旋结构的组成部分,

这可能导致细胞死亡,
除非损伤得到修复。

由于癌细胞繁殖迅速,

它们会吸收高浓度
的烷化剂,

而且它们的 DNA 经常暴露
并且很少被修复。

因此,它们
比大多数其他细胞更容易死亡,

后者有时间修复受损的 DNA,

并且不会积累相同
浓度的烷化剂。

另一种形式的化学疗法涉及
称为微管稳定剂的化合物。

细胞有小管,它们组装
起来帮助细胞分裂

和 DNA 复制,然后分解。

当微管稳定剂
进入细胞内时,

它们会阻止这些微小的
管子分解。

这会阻止细胞
完成复制,从而导致其死亡。

这些只是我们今天用来治疗癌症的
六类化疗药物中的两个例子

但是,尽管有巨大的好处,
化学疗法有一个很大的缺点:

它会影响身体
中自然必须快速更新的其他健康细胞。

毛囊、口腔细胞
、胃肠道内壁

、生殖系统和骨髓
受到的打击几乎与癌症一样严重。

与癌细胞类似
,这些正常细胞的快速产生

意味着它们
更频繁地获取资源——

因此更容易受到
化疗药物的影响。

这会导致化疗的几种常见
副作用,

包括脱发、疲劳、不孕、
恶心和呕吐。

医生通常会开一些选项
来帮助控制这些副作用,

例如强效抗恶心药物。

对于脱发,称为冷帽的装置
可以帮助降低

头部周围的温度并
收缩血管,

从而限制
到达毛囊的化疗药物的数量。

一旦一个疗程的化疗
结束,

受到药物严重影响的健康组织
就会恢复

并开始像往常一样更新。

仅在 2018 年,全球就有超过 1700 万人
接受了癌症诊断。

但化疗和其他
治疗改变了许多人的前景。

只需考虑一个事实,由于治疗的进步,多达 95
% 的睾丸癌患者

能够幸存下来

即使在患有急性髓性
白血病(一种侵袭性血癌)的患者中,

化疗也使大约
60% 的 60 岁以下患者在

第一阶段治疗后病情缓解。

研究人员仍在开发
更精确的干预措施

,只针对预期的
癌细胞。

这将有助于提高存活率,
同时

减少对健康组织的伤害,

使我们在抗击癌症方面拥有的最佳工具之一
变得更好。