Please perform an academic literature review on the prevailing opinions about chemosensitivity testing (aka "functional testing").
Hello there, thank you for using Wonder! I'll provide an answer to your question about an academic literature review on the prevailing opinions about chemosensitivity testing. The short version is that they are mostly positive reviews from scientists about the effectiveness of chemosensitivity tests in cancer treatment. ATP, Kern's, HYDRA and other modern methods have mostly positive reviews while cell culture-based methods of chemosensitivity have got mainly negative reviews.
Find a deep dive into my research methodology and findings below.
I focused my search on authoritative studies and reviews by medical practitioners published in the last three years. I made an effort to find information pertaining to blood cancers in particular. Though I found none, I am confident that most of the the reviews and study results I found apply to cancer in general, including blood cancers.
Chemotherapy is one of the major treatments for cancer patients but it provides benefits to only 30% to 70% of patients. Chemosensitivity testing can be used to predict or determine the effectiveness of several treatment methods for a particular patient. Chemosensitivity tests are grouped into three groups:
Histoculture Drug Response Assays (HDRA). These tests are used to determine the overall effect of drug viability proliferation and metabolism of tumor cells. These methods are especially useful in clinical outcome follow-up. MTT, ATP, DISC, Kern's and clonogenic assays are some of the methods in the modern use.
Molecular Biology Techniques. These methods are used in the study of the structure and function of DNA, RNA, and proteins in the cancer cells. They are also used in predicting drug response.
In Vivo Predicting Response Method. These methods are favored by many medical practitioners because of their convenience, repeatability, and non-invasiveness. They are particularly effective in selecting effective anti-cancer drugs and monitoring drug resistance markers.
An article by Yongzhuang Su published in the Journal of cancer therapy notes that there is no chemosensitivity testing method that is universally used by the medical community. Different methods are used for different tumors and for various drugs.
Chemosensitivity testing has been in use since the 1940s and has, therefore, stood the test of time. The methods have evolved over the years. "Clonogenic assays were believed to have promise in the 1970s", but because of their low evaluation rates and limited use, they have fallen out of favor. Currently, MTT, ATP, DISC, and Kern's assays are more widely used. It is, therefore, reasonable to assume that new methods will continue to be developed to improve the limitations of the current ones.
CELL CULTURE-BASED CHEMOSENSITIVITY TESTS
Cell culture-based chemosensitivity tests are not widely used because of low success rates, long period of time required, and the poor correlation with the clinical response. In fact, the American Society of Clinical Oncology (ASCO) in its latest guidelines (2011) does not recommend the use of Chemotherapy Sensitivity and Resistance Assays (CSRAs) to select chemotherapeutic agents for individual patients outside of the clinical trial setting.
LIMITATIONS OF CHEMOSENSITIVITY TESTS
The effectiveness of chemosensitivity testing is still under debate. Below are some of the reasons given by practitioners who are hesitant to embrace the tests.
Varied Response Rates. Because of heterogeneity and differences in drug sensitivity of tumors, there are differences in response rates, for example between the patients with the same pathological diagnosis. It is known that lymph node metastatic tumors are less resistant than hepatic metastatic tumors. In some cases, cells from different locations in the same tumor have different sensitivity to the drug. This makes chemosensitivity tests unreliable in some situations.
Sometimes the microenvironment of a tumor is different in vivo compared to in vitro. The test can reveal different results in this case. However, it is widely agreed that the tests can be good references in such cases.
The toxicity of the of drugs on surrounding cells. In cases where a drug is as strong on the surrounding cells as it is on the tumor cells, chemosensitivity tests might not give reliable results.
Yongzhuang Su reported that chemosensitivity testing costs range from $1,000 to $4,000. These are seen as prohibitive to some.
Other doctors are critical of the effectiveness of chemosensitivity testing, particularly among lung cancer patients. In this review, Dr. Pinder claims that he's not aware of any randomized trials demonstrating a single benefit of chemosensitivity testing in lung cancer patients.
THE APPLICATIONS OF CHEMOSENSITIVITY TESTS
Several studies have demonstrated a correlation between in vitro testing result and in vivo outcomes. For example, a study on patients with non-small cell lung cancer who received pre-surgical adjuvant chemotherapy with the help of the chemosensitivity assessments over two months enabled medics to quickly and accurately assess the effectiveness of the treatment, prompting the early withdrawal of treatment in cases where it was failing.
A Study published in the Journal of Biotechnology in 2016 cites chemosensitivity as one of the factors that are leading to improved prognosis of medulloblastoma tumor patients.
The tests have been successfully used for predicting of patient outcomes of patients with metastatic Colorectal Cancer CRC. CRC is the third most common cancer and the fourth most frequent cause of cancer death worldwide . Chemosensitivity assays and biomarkers are used to minimize drug toxicity and to optimize the efficacy in CRC patients.
Studies that focus on HYDRA techniques of chemosensitivity have shown the usefulness of the tests. The correlation rate of HDRA clinical response was reported to be as high as 92.1%in different studies. Examples here and here.
To sum it up, they are mostly positive reviews from experts about chemosensitivity testing. Cell-culture based tests have got universally negative reviews because of poor results and invasiveness. However, HYDRA, ATP, Kern’s and similar modern tests have largely garnered positive reviews, with several authoritative studies backing them up. Limitations of these modern tests include inconsistent results and prohibitive costs. But the fact that chemosensitivity tests have stood the test of time indicates that they have a bright future.
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