Related Experiment Video

Updated: Feb 7, 2026

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
09:29

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies

Published on: September 30, 2016

14.4K

Cachectic Cancer Patients: Immune to Checkpoint Inhibitor Therapy?

Christopher C Coss1,2, Steven K Clinton2,3, Mitch A Phelps4,2

  • 1Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, Ohio. coss.16@osu.edu.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|July 19, 2018
PubMed

Insights

Cancer cachexia complicates immunotherapy. Patients with cancer cachexia show faster drug metabolism and reduced effectiveness of immune checkpoint inhibitors like pembrolizumab.

Area of Science:

  • Oncology
  • Immunotherapy
  • Pharmacology

Background:

  • Immune checkpoint inhibitors (ICIs) have transformed cancer treatment, improving outcomes in various malignancies.
  • However, responses to ICIs are heterogeneous and not fully understood.
  • Cancer cachexia presents a significant challenge in optimizing ICI efficacy.

Purpose of the Study:

  • To investigate the impact of cancer cachexia on the pharmacokinetics and response to immune checkpoint inhibition.
  • To elucidate mechanisms underlying the altered drug metabolism in cachectic cancer patients.

Main Methods:

  • Analysis of patient data including cancer types, cachexia status, and treatment response.
  • Pharmacokinetic studies to measure drug clearance (e.g., pembrolizumab).
  • Correlation of clinical outcomes with pharmacokinetic parameters and cachexia markers.

Main Results:

  • Cachectic cancer patients demonstrated significantly elevated pembrolizumab clearance compared to non-cachectic individuals.
  • Higher drug clearance in cachectic patients was associated with poorer treatment response to pembrolizumab.
  • Cancer cachexia is identified as a key factor influencing ICI efficacy.

Conclusions:

  • Cancer cachexia significantly impacts the pharmacokinetics of immune checkpoint inhibitors, leading to reduced therapeutic effectiveness.
  • Addressing cancer cachexia is crucial for improving patient outcomes in ICI therapy.
  • Further research is needed to develop strategies to mitigate the negative effects of cachexia on immunotherapy.

More Related Videos

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts10:27

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

Published on: July 25, 2020

8.0K
Cerenkov Luminescence Imaging CLI for Cancer Therapy Monitoring08:45

Cerenkov Luminescence Imaging CLI for Cancer Therapy Monitoring

Published on: November 13, 2012

14.3K

Related Concept Videos

Cancer Therapies02:49

Cancer Therapies

Cancer therapies are various modes of treatment, such as surgery, radiation therapy, and chemotherapy that are administered to cancer patients.
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
10.2K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
8.9K
The Spindle Assembly Checkpoint02:19

The Spindle Assembly Checkpoint

The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
3.9K
Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
11.0K
What is the Immune System?01:38

What is the Immune System?

Overview
130.8K
Gene Therapy00:59

Gene Therapy

Gene therapy is a technique where a gene is inserted into a person’s cells to prevent or treat a serious disease. The added gene may be a healthy version of the gene that is mutated in the patient, or it could be a different gene that inactivates or compensates for the patient’s disease-causing gene. For example, in patients with severe combined immunodeficiency (SCID) due to a mutation in the gene for the enzyme adenosine deaminase, a functioning version of the gene can be...
27.7K