One of the challenges in cancer treatment is the development of resistance against anti-cancer drugs. It would be necessary to switch to new drugs, but knowing which drugs are the most effective for the patient is difficult, and testing different drugs puts the patient at risk. Mouse “avatars” might be a rescue.
The term “avatars” are informally given by cancer researchers to refer to mice or other animals with human tissue implanted onto them. More formally, these models are known as xenografts (implantation of a tissue donated from one species onto a recipient of another species). Patient-derived human tumor tissue xenograft models are made by implanting mice with a portion of patient’s tumor tissues. The expectation is heightening in the recent years as researchers hope that this method will guide us to personalized cancer therapy.
Ideally, clinicians would like to have a line-up of drugs for a patient so that by the time the patient’s cancer develops resistance against a particular drug, new drugs and treatment methods are ready at hand. The use of xenograft models may allow for this situation. The advantage of using a personalized xenograft model is that a large number of cancer drugs can be tested for their effectiveness on a particular patient before giving the drugs to the patient. The technique also reduces the risk for patients by allowing for pre-screening of the drugs before application.
In addition, xenograft model often resembles the tumor in the patient better than cultured cancer cells on a petri dish, and thus it is a better method for screening drugs before clinical trials. Since only ~5% of the potential anti-cancer drugs make it through preclinical tests and clinical trials, researchers are hoping that xenograft models serve as the improved method for predicting the performance of the drugs in clinical trials.
Mouse avatars have already been shown useful in the treatment of several advanced-stage cancer patients, including pancreatic, prostate, and adenoid cystic cancers. In particular, a case report of a patient with advanced pancreatic cancer has shown that a certain drug found effective in treatment of the patient’s personalized xenograft mice was also effective on the patient. The patient was symptom-free for three years after the new treatment, whereas the average survival rate for the condition is three months.
However, avatars are not perfect yet, and there are still challenges and limitations with this method. For one thing, it is difficult to make xenografts. Success rates of tumor implantation depend according to cancer types, and it can be as low as <1% in prostate cancer and ~9% in breast cancer. In addition, the creation of xenograft models and drug screening take about 6-8 months, a length of time many patients cannot wait. The technique involves a long-term collaboration and joint effort among clinicians, biologists, scientists, and patients. Hopefully, we will start seeing more examples of successful cancer treatment using xenograft models.
Thank you for reading this post, and see you next week!
Mouse ‘avatars’ could aid pancreatic cancer therapy
Personalizing Cancer Treatment in the Age of Global Genomic Analyses: PALB2 Gene Mutations and the Response to DNA Damaging Agents in Pancreatic Cancer
Prioritizing Phase I Treatment Options Through Preclinical Testing on Personalized Tumorgraft
Next Generation Sequencing of Prostate Cancer from a Patient Identifies a Deficiency of Methylthioadenosine Phosphorylase, an Exploitable Tumor Target
Primary human tumor xenografted models (‘tumorgrafts’) for good management of patients with cancer
Patient-derived human tumour tissue xenografts in immunodeficient mice: a systematic review