READING

READING PASSAGE 1
You should spend about 20 minutes on Questions 1–13, which are based on
Reading Passage 1 on pages 12 and 13.
Questions 1–7
Reading Passage 1 has seven sections, A–G.
Choose the correct heading for each section from the list of headings below.
Write the correct number, i–x, in boxes 1–7 on your answer sheet.

List of Headings
iUnsatisfactory outcomes
iiThe benefits of the new method for various diseases
iiiAn obscure origin
ivTreatment efficacy still to be assessed
vDisappointment at the lack of development
viNo exact answer
viiPatients with uncommon symptoms
viiiA shift in focus
ixSomething atypical of its kind
xThe importance of the new direction

1 Section A
2 Section B
3 Section C
4 Section D
5 Section E
6 Section F
7 Section G

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Test 3

Understanding cancer’s secret syndrome

Revealing the molecular make-up of cancer cells could help scientists
develop therapies for one of the most dangerous and puzzling forms of the disease

A The patients who walk into Alwin Krämer’s clinic are seeking medical help for a range
of symptoms. There’s a woman who has found a lump in her armpit but feels otherwise
well, another is experiencing frequent headaches and blurred vision, while a middle-
aged man has been suffering from ongoing stomach pain. Because their symptoms
are so vague and non-specific, it has often taken months for their general practitioners
to refer them for further investigations. Then an MRI or ultrasound scan reveals a
suspicious growth and a biopsy confirms cancer. Even so, these are no ordinary
cancer patients.
B In most cancer patients, the tumour is discovered at the location in the body where a
genetic mutation has prompted a cell to start growing uncontrollably. Cells sometimes
break off from this ‘primary site’ and seed additional tumours – metastases –
elsewhere in the body. But it is the primary tumour which raises the alarm. However,
Krämer specialises in the diagnosis and treatment of cancer of unknown primary
(CUP) syndrome, where the discovered tumour bears little relationship to the organ or
tissue it is growing in.
C This suggests it is the product of one of these cancer seeds – yet the primary tumour
that released them either eludes detection or has mysteriously vanished. There are
various theories, none of them definitive. For instance, in a handful of documented
cases a patient’s primary tumour was destroyed by their immune system, while their
metastases continue to grow. Something similar may be happening in CUP patients.
Alternatively, the primary tumour may be too small and slow growing to be detected.
But some of its cells have developed mutations which make them more aggressive
and prone to peeling off, resulting in faster-growing metastases.
D In the past decade, molecular sequencing methods have emerged which should have
made this hunt for the primary tumour easier. By studying the pattern of gene
expression with RNA as well as genetic and epigenetic markers on tumour cell DNA, it
is possible to identify a tumour’s tissue of origin. The hope was that doing so would
lead to improvements in patients’ survival. But the results of two recent studies using
RNA-based methods to decide which treatment CUP patients should receive, have
been disappointing: ‘Neither showed an advantage for the gene expression based
treatment,’ says Krämer.
E Now there is a different approach based on a growing sense that CUP may be a
specific type of cancer itself, one that is characterised by the very early or immediate
spread of metastases rather than the growth of a single primary tumour. That’s why
the primary tumour may not be found. Cancers also constantly evolve. And a
metastatic tumour may carry different ‘driver’ mutations to the primary tumour. So
rather than trying to identify a CUP’s tissue of origin, scientists are now using genomic
techniques to pinpoint these driver mutations and using this information to inform
patient treatment instead.

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 Reading

F Although various types of genomic alteration can lead to cancer, no single sequencing
method can identify all of them, so multiple tests are run in parallel to single out driver
mutations which might be targeted with specific drugs. For instance, a CUP patient
whose tumour harbours a specific mutation in the BRCA1 or BRCA2 gene might be
offered a drug called a PARP inhibitor that exploits a weakness in cells carrying these
mutations, triggering their destruction. One study which analysed tissue from 200 CUP
patients found 85 percent of them had at least one clinically relevant mutation which
could be used to personalise their therapy. Clinical trials are currently underway to test
whether this new approach to treating CUP syndrome has any impact on patients’
survival. If it does, this could herald a new approach to treating cancer more generally.
The current approach hinges on early diagnosis and the removal of the primary
tumour, accompanied by drugs or radiotherapy to destroy any embryonic metastases.
But once metastases become established, the disease becomes much harder to treat.
G Yet mounting evidence from animal studies suggests that metastasis may occur far
earlier than had been assumed, and that these tumour seeds develop independently,
acquiring new mutations. CUP patients may be suffering from this extreme end of
normal cancer evolution. That’s why a better understanding of the molecular
signatures associated with CUP syndrome may provide new insights into the biology of
metastasis more generally, as well as alternative ways to treat it. Since 2017, three
drugs have been approved for the treatment of tumours which harbour specific
mutations – regardless of where they occur in the body. The dawn of such ‘tumour-
agnostic’ therapy is good news for patients with CUP syndrome because most
targeted therapies are only approved for use in anatomically defined cancers, for
example in the lung or colorectal area. But it is also good news for anyone with an
aggressive tumour. ‘Maybe it really doesn’t matter if you say someone has this or that
cancer, or someone has a CUP syndrome, in the end it is the mutational spectrum and
the molecular features that define a certain individual cancer, and not the organ where
the primary tumour has developed,’ Krämer says.

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Test 3

Questions 8–13
Complete the notes below.
Choose NO MORE THAN TWO WORDS from the passage for each answer.
Write your answers in boxes 8–13 on your answer sheet.
Cancer treatment

Conventional approach
 aimed at identifying the 8 ……………………
 capable of destroying 9 …………………… in an early stage
 far less useful when metastases are 10 ……………………

RNA-based method
 ineffective in prolonging 11 ……………………

Genomic technique
 employed to detect 12 ……………………

PARP inhibitor drugs:

 used to kill BRCA1 and BRCA2 defective 13 …………………