A patient-derived orthotopic xenograft (PDOX) nude-mouse model precisely identifies effective and ineffective

Zhiying Zhang1, Kaiwen Hu2, Tasuku Kiyuna3

  • 1AntiCancer, Inc., 7917 Ostrow Street, San Diego, CA 92111, USA; Department of Surgery, University of California San Diego, CA 92103, USA; Department of Oncology, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, 100078, China.

Pharmacological Research
|February 27, 2019
PubMed

Insights

Patient-derived orthotopic xenograft (PDOX) models effectively identified effective treatments for leiomyosarcoma, a rare cancer. Gemcitabine/docetaxel, trabectedin, and temozolomide showed promise, unlike standard doxorubicin therapy.

Area of Science:

  • Oncology
  • Translational Cancer Research
  • Preclinical Cancer Models

Background:

  • Leiomyosarcoma is a rare and challenging cancer.
  • Current first-line treatments like doxorubicin are often ineffective.
  • Personalized cancer therapy requires accurate predictive models.

Purpose of the Study:

  • To evaluate the efficacy of various chemotherapeutic agents in a patient-derived orthotopic xenograft (PDOX) model of leiomyosarcoma.
  • To determine if the PDOX model can predict treatment response for leiomyosarcoma.

Main Methods:

  • A recurrent leiomyosarcoma tumor was implanted into the femoral muscle of nude mice to create a PDOX model.
  • The model was treated with doxorubicin, gemcitabine/docetaxel, trabectedin, temozolomide, pazopanib, and olaratumab.
  • Treatment efficacy was assessed based on tumor response within the PDOX model.

Main Results:

  • Gemcitabine/docetaxel, trabectedin, and temozolomide demonstrated high efficacy in the leiomyosarcoma PDOX model.
  • Doxorubicin, pazopanib, and olaratumab were ineffective in this model.
  • The PDOX model successfully differentiated between effective and ineffective treatments.

Conclusions:

  • The patient-derived orthotopic xenograft model is a valuable tool for predicting treatment efficacy in leiomyosarcoma.
  • This model can aid in individualizing therapy for patients with rare and recalcitrant leiomyosarcoma.
  • Effective agents identified include gemcitabine/docetaxel, trabectedin, and temozolomide.

Related Concept Videos

Modeling in Therapy01:26

Modeling in Therapy

Modeling, a key technique in therapy, uses observational learning to help clients acquire and practice new skills by watching therapists demonstrate desired behaviors. This approach, rooted in Albert Bandura's concept of vicarious learning, plays a significant role in therapeutic interventions for various psychological conditions, including social anxiety, ADHD, and depression.
Participant Modeling
Participant modeling involves therapists demonstrating calm and effective behaviors in...
433
Pharmacodynamics in Geriatric Patients: Effects of Age01:27

Pharmacodynamics in Geriatric Patients: Effects of Age

Age-related pharmacokinetic changes are extensively documented, but understanding age-related pharmacodynamic alterations is relatively limited. This knowledge gap can be partly attributed to the complexity of developing appropriate measures of drug responses compared to bioanalytical methods for determining drug concentrations.Most information regarding age-related differences in human pharmacodynamics originates from cross-sectional studies. However, these studies assume that observed mean...
202
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...
27.6K
Directing and Steric Effects in Disubstituted Benzene Derivatives01:18

Directing and Steric Effects in Disubstituted Benzene Derivatives

When disubstituted benzenes undergo electrophilic substitution, the product distribution depends on the directing effect of both substituents. When the directing effects of both substituents reinforce each other, a single product is obtained. For example, bromination of p-nitrotoluene occurs ortho to the methyl group and meta to the nitro group, which is the same position, resulting in a single product. However, if the directing effects of the two groups oppose each other, the...
4.0K
Uncertainty in Measurement: Accuracy and Precision03:37

Uncertainty in Measurement: Accuracy and Precision

Scientists typically make repeated measurements of a quantity to ensure the quality of their findings and to evaluate both the precision and the accuracy of their results. Measurements are said to be precise if they yield very similar results when repeated in the same manner. A measurement is considered accurate if it yields a result that is very close to the true or the accepted value. Precise values agree with each other; accurate values agree with a true value. 
100.9K
Accuracy and Precision01:52

Accuracy and Precision

Scientists typically make repeated measurements of a quantity to ensure the quality of their findings and to evaluate both the precision and the accuracy of their results. Measurements are said to be precise if they yield very similar results when repeated in the same manner. A measurement is considered accurate if it yields a result that is very close to the true or the accepted value. Precise values agree with each other; accurate values agree with a true value.  Highly accurate...
15.2K