PRIMEVIEW

CANCER-ASSOCIATED CACHEXIA
For the Primer, visit doi:10.1038/nrdp.2017.105

Cachexia is a disorder characterized Active MANAGEMENT

OUTLOOK research areas
by the involuntary loss of body weight,
in cancer‑associated
with loss of homeostatic control of both

TRA
cachexia include the The provision of adequate nutrition through
energy and protein balance. Cancer-
basic mechanisms that supplements or provision of more and

NS L
associated cachexia leads to progressive
underlie the clinical high‑quality food is the mainstay of cachexia

ATI
functional impairment, cancer-related phenotypes and treatment. Patients who cannot take food in

O
mortality, treatment-related complications treatment

NA
orally (for example, owing to obstruction of the
and poor quality of life. approaches.

LR
oesophagus) are offered enteral or parenteral

ES
nutritional support. Research is underway

EA
Aetiology‑based
to find methods to address the metabolic

RC
MECHANISMS diagnostic criteria
aspects of cancer-associated cachexia, which

H
for cancer-associated
cannot be overcome by nutrition alone.
cachexia are needed.
Sarcopenia (skeletal muscle depletion) is a key Furthermore, patients require adequate pain
Biomarkers are being
feature of cancer-associated cachexia; other sought, using genomics and symptom management.
tissues — including adipose tissue — and metabolomics
are also affected. Patients with cancer approaches. Contributors of weight loss that
often have reduced food intake (which can be treated include pain, nausea,
affects weight), decreased synthesis of vomiting, problems swallowing, early
muscle protein and increased muscle catabolism. satiety, oesophageal obstruction, anxiety,
Understanding how these factors interact is the RCH depression, distress and inability to sleep
SEA Mechanistic
subject of intense research that relies heavily C RE
B ASI insights continue to emerge from
on animal models as collecting data in patients studies in animal models. For example, the roles
is often difficult owing to patient vulnerability. of skeletal muscle stem cells and bone metastases in
Cancer affects the normal homeostatic control of cachexia are being examined. QUALITY OF LIFE
energy balance, and tumours produce a range of
factors that are thought to contribute to cachexia.
Amongst these, pro-inflammatory mediators — Negative interactions with food and eating occur
L RE SEARCH
including tumour necrosis factor (TNF) and IL-6 IC A at every stage of cancer-associated cachexia;
IN
— have been shown to promote (through their CL the taste, smell and texture of food can become
Building on the mechanistic and
respective signalling cascades) the transcription of unpleasant for patients. Additionally, chewing
biomarker insights will be the
ubiquitin–proteasome and autophagy components, and swallowing can be painful, early satiety
development of targeted therapies
which contribute to enhanced breakdown of to address the catabolic processes makes patients feel too full to continue eating
skeletal muscle. of cancer-associated cachexia. and patients express distress
Additionally, the design of clinical about weight loss and
TNF IL-6 TGFβ Myostatin not eating enough.
trials and the end points used are
TWEAK IFNγ Activins evolving with the aim of avoiding Importantly, patients are
confounding factors such as death, highly aware of death
EPIDEMIOLOGY dropout and missing data. as the ultimate result of
the weight loss, further
↑ Transcription Half of all cancer deaths pulmonary, cancer stage, male adding to their distress.
Ubiquitin proteasome genes Skeletal worldwide are attributed to hepatic and colorectal sex, advanced age, genetic
Autophagy genes muscle the cancers most frequently cancers. Risk factors for factors, comorbidities and
breakdown
associated with cachexia: developing cachexia have been administration of several drugs
pancreatic, oesophageal, gastric, identified and include advanced used in cancer therapy.

Written by Mina Razzak; designed by Laura Marshall Article number: 17106; doi:10.1038/nrdp.2017.106; published online 18 Jan 2018
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