The Role of Muscle Cachexia in Pancreatic Cancer
| Status: | Recruiting |
|---|---|
| Conditions: | Cancer, Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - 80 |
| Updated: | 10/28/2018 |
| Start Date: | March 2016 |
| End Date: | December 2025 |
| Contact: | Jose G Trevino, MD |
| Email: | jose.trevino@surgery.ufl.edu |
| Phone: | 352-266-0761 |
The relationship between myopenia, nutritional status, and long-term oncologic outcomes
remains poorly characterized in patients with anatomically resectable pancreatic cancer (PC).
The investigators want to look at muscle properties in pancreatic cancer patients to
determine possible therapeutic options toward better nutritional status. Patients with benign
right upper quadrant pathology will be utilized as controls for the study.
The researchers hypothesize that improving cancer cachexia in PC will improve the quality of
life and ultimately increase overall survival. The long term goal of is to identify areas of
intervention to prevent and/or improve cachectic events in PC in order to significantly
improve clinical outcomes. The first step in this long term goal is to fully characterize
cachexia in the condition of PC. This research is to understand and modify the local response
within skeletal muscle leading to a clinically relevant persistent wasting and to understand
and interrupt the systemic stimulus produced by the tumor local environment resulting in
these muscle specific mechanisms.
remains poorly characterized in patients with anatomically resectable pancreatic cancer (PC).
The investigators want to look at muscle properties in pancreatic cancer patients to
determine possible therapeutic options toward better nutritional status. Patients with benign
right upper quadrant pathology will be utilized as controls for the study.
The researchers hypothesize that improving cancer cachexia in PC will improve the quality of
life and ultimately increase overall survival. The long term goal of is to identify areas of
intervention to prevent and/or improve cachectic events in PC in order to significantly
improve clinical outcomes. The first step in this long term goal is to fully characterize
cachexia in the condition of PC. This research is to understand and modify the local response
within skeletal muscle leading to a clinically relevant persistent wasting and to understand
and interrupt the systemic stimulus produced by the tumor local environment resulting in
these muscle specific mechanisms.
Cancer cachexia (CC) is a devastating condition affecting up to 80% of cancer patients,
diminishing quality of life and contributing to increased mortality. Cancer cachexia is a
complex metabolic syndrome characterized by the loss of skeletal muscle mass and weakness.
The muscle pathology of cancer cachexia is not only related to muscle atrophy but also to
disruptions to the contractile apparatus of the muscle. While physiologic disruptions in
muscle sarcomere and myofiber membrane integrity have been observed despite the lack of
injury, the totality of the muscle specific mechanisms contributing to these phenotypes have
not been described, nor investigated in the context of pancreatic cancer (PC) where cachexia
is a significant clinical problem. Therefore, delineating specific mechanisms of muscle
catabolism in PC is critical to developing clinical therapies to control wasting and improve
patient quality of life, clinical outcomes and long-term survival.
A variety of tumor promoting and inflammatory cell signaling pathways have been implicated in
cancer cachexia, whereby pro-inflammatory cytokines have been implicated as a driving force.
Remarkably, approximately half of all patients with PC demonstrate a measurable acute phase
response, which is associated with poor clinical outcomes. Importantly, systemic elevations
of these inflammatory mediators are due to a complex local interplay between the developing
tumor and the immune system which subsequently leads to a systemic chronic inflammatory
state. PC appears to manipulate the immune system to promote its survival at the expense of
nutritional stores which results in cachexia. Therefore, understanding of the local and
systemic inflammatory response in PC and its relation to muscle specific mechanisms is
crucial to developing effective therapies for cancer cachexia.
PC associated cachexia results in a significant therapeutic dilemma. Local approaches such as
surgery for curative intent encounter a high recurrence rate which is indicative of the
systemic nature of even very early-stage disease. Therefore, systemic therapies are necessary
for long-term survival. Unfortunately, effective chemotherapies are only offered to patients
with good clinical parameters such as nutritional status. In other words, if the patient is
too weak, they are not offered effective therapies for the risk of causing more harm than
good.
diminishing quality of life and contributing to increased mortality. Cancer cachexia is a
complex metabolic syndrome characterized by the loss of skeletal muscle mass and weakness.
The muscle pathology of cancer cachexia is not only related to muscle atrophy but also to
disruptions to the contractile apparatus of the muscle. While physiologic disruptions in
muscle sarcomere and myofiber membrane integrity have been observed despite the lack of
injury, the totality of the muscle specific mechanisms contributing to these phenotypes have
not been described, nor investigated in the context of pancreatic cancer (PC) where cachexia
is a significant clinical problem. Therefore, delineating specific mechanisms of muscle
catabolism in PC is critical to developing clinical therapies to control wasting and improve
patient quality of life, clinical outcomes and long-term survival.
A variety of tumor promoting and inflammatory cell signaling pathways have been implicated in
cancer cachexia, whereby pro-inflammatory cytokines have been implicated as a driving force.
Remarkably, approximately half of all patients with PC demonstrate a measurable acute phase
response, which is associated with poor clinical outcomes. Importantly, systemic elevations
of these inflammatory mediators are due to a complex local interplay between the developing
tumor and the immune system which subsequently leads to a systemic chronic inflammatory
state. PC appears to manipulate the immune system to promote its survival at the expense of
nutritional stores which results in cachexia. Therefore, understanding of the local and
systemic inflammatory response in PC and its relation to muscle specific mechanisms is
crucial to developing effective therapies for cancer cachexia.
PC associated cachexia results in a significant therapeutic dilemma. Local approaches such as
surgery for curative intent encounter a high recurrence rate which is indicative of the
systemic nature of even very early-stage disease. Therefore, systemic therapies are necessary
for long-term survival. Unfortunately, effective chemotherapies are only offered to patients
with good clinical parameters such as nutritional status. In other words, if the patient is
too weak, they are not offered effective therapies for the risk of causing more harm than
good.
Inclusion Criteria:
- Pancreatic Cancer Patients who are potentially surgically resectable.
Exclusion Criteria:
- Patients who do not meet the criteria for surgical resection.
We found this trial at
1
site
Click here to add this to my saved trials
