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Novel targeted therapies for cancer cachexia.

Abstract Anorexia and metabolic alterations are the main components of the cachectic syndrome. Glucose intolerance, fat depletion, muscle protein catabolism and other alterations are involved in the development of cancer cachexia, a multi-organ syndrome. Nutritional approach strategies are not satisfactory in reversing the cachectic syndrome. The aim of the present review is to deal with the recent therapeutic targeted approaches that have been designed to fight and counteract wasting in cancer patients. Indeed, some promising targeted therapeutic approaches include ghrelin agonists, selective androgen receptor agonists, β-blockers and antimyostatin peptides. However, a multi-targeted approach seems absolutely essential to treat patients affected by cancer cachexia. This approach should not only involve combinations of drugs but also nutrition and an adequate program of physical exercise, factors that may lead to a synergy, essential to overcome the syndrome. This may efficiently reverse the metabolic changes described above and, at the same time, ameliorate the anorexia. Defining this therapeutic combination of drugs/nutrients/exercise is an exciting project that will stimulate many scientific efforts. Other aspects that will, no doubt, be very important for successful treatment of cancer wasting will be an optimized design of future clinical trials, together with a protocol for staging cancer patients in relation to their degree of cachexia. This will permit that nutritional/metabolic/pharmacological support can be started early in the course of the disease, before severe weight loss occurs. Indeed, timing is crucial and has to be taken very seriously when applying the therapeutic approach.
PMID
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Authors

Mayor MeshTerms
Keywords

cachexia

drug therapy

muscle wasting

Journal Title the biochemical journal
Publication Year Start




PMID- 28751550
OWN - NLM
STAT- MEDLINE
DA  - 20170728
DCOM- 20170803
LR  - 20170803
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 474
IP  - 16
DP  - 2017 Jul 27
TI  - Novel targeted therapies for cancer cachexia.
PG  - 2663-2678
LID - 10.1042/BCJ20170032 [doi]
AB  - Anorexia and metabolic alterations are the main components of the cachectic
      syndrome. Glucose intolerance, fat depletion, muscle protein catabolism and other
      alterations are involved in the development of cancer cachexia, a multi-organ
      syndrome. Nutritional approach strategies are not satisfactory in reversing the
      cachectic syndrome. The aim of the present review is to deal with the recent
      therapeutic targeted approaches that have been designed to fight and counteract
      wasting in cancer patients. Indeed, some promising targeted therapeutic
      approaches include ghrelin agonists, selective androgen receptor agonists,
      beta-blockers and antimyostatin peptides. However, a multi-targeted approach
      seems absolutely essential to treat patients affected by cancer cachexia. This
      approach should not only involve combinations of drugs but also nutrition and an 
      adequate program of physical exercise, factors that may lead to a synergy,
      essential to overcome the syndrome. This may efficiently reverse the metabolic
      changes described above and, at the same time, ameliorate the anorexia. Defining 
      this therapeutic combination of drugs/nutrients/exercise is an exciting project
      that will stimulate many scientific efforts. Other aspects that will, no doubt,
      be very important for successful treatment of cancer wasting will be an optimized
      design of future clinical trials, together with a protocol for staging cancer
      patients in relation to their degree of cachexia. This will permit that
      nutritional/metabolic/pharmacological support can be started early in the course 
      of the disease, before severe weight loss occurs. Indeed, timing is crucial and
      has to be taken very seriously when applying the therapeutic approach.
CI  - (c) 2017 The Author(s); published by Portland Press Limited on behalf of the
      Biochemical Society.
FAU - Argiles, Josep M
AU  - Argiles JM
AD  - Cancer Research Group, Departament de Bioquimica i Biomedicina Molecular,
      Facultat de Biologia, Universitat de Barcelona, Diagonal 643, Barcelona 08028,
      Spain [email protected]
AD  - Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Spain.
FAU - Lopez-Soriano, Francisco Javier
AU  - Lopez-Soriano FJ
AD  - Cancer Research Group, Departament de Bioquimica i Biomedicina Molecular,
      Facultat de Biologia, Universitat de Barcelona, Diagonal 643, Barcelona 08028,
      Spain.
AD  - Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Spain.
FAU - Stemmler, Britta
AU  - Stemmler B
AD  - BS Nutrition Centre, 08195 Barcelona, Spain.
FAU - Busquets, Silvia
AU  - Busquets S
AD  - Cancer Research Group, Departament de Bioquimica i Biomedicina Molecular,
      Facultat de Biologia, Universitat de Barcelona, Diagonal 643, Barcelona 08028,
      Spain.
AD  - Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Spain.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20170727
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Adrenergic beta-Antagonists)
RN  - 0 (Androgen Receptor Antagonists)
RN  - 0 (Ghrelin)
RN  - 0 (MSTN protein, human)
RN  - 0 (Myostatin)
RN  - 0 (Peptides)
SB  - IM
MH  - Adrenergic beta-Antagonists/therapeutic use
MH  - Androgen Receptor Antagonists/therapeutic use
MH  - Anorexia/metabolism/pathology/therapy
MH  - Cachexia/metabolism/pathology/*therapy
MH  - Diet Therapy/methods
MH  - Exercise Therapy/methods
MH  - Ghrelin/agonists
MH  - Humans
MH  - Myostatin/antagonists & inhibitors/metabolism
MH  - Neoplasms/metabolism/pathology/*therapy
MH  - Peptides/therapeutic use
OTO - NOTNLM
OT  - cachexia
OT  - drug therapy
OT  - muscle wasting
EDAT- 2017/07/29 06:00
MHDA- 2017/08/05 06:00
CRDT- 2017/07/29 06:00
PHST- 2017/04/13 [received]
PHST- 2017/06/21 [revised]
PHST- 2017/06/23 [accepted]
AID - BCJ20170032 [pii]
AID - 10.1042/BCJ20170032 [doi]
PST - epublish
SO  - Biochem J. 2017 Jul 27;474(16):2663-2678. doi: 10.1042/BCJ20170032.