With an invitation to the 2023 American Association for Cancer Research (AACR) meeting in Orlando, we reported results with our ex vivo analysis of programmed cell death (EVA/PCD™) in over 10,000 cancer patients (Nagourney, AACR April 18, 2023: 4910).
This included over 2000 ovarian, 1800 breast, 1000 lung and almost 900 colorectal cancers. Indeed, virtually every type of cancer has been studied from pancreatic (400) and hematologic (900) to sarcoma (400), prostate (100), and brain (100).
Survival curves from our peer-reviewed published studies confirmed that patients who receive laboratory-directed therapy have superior response, time-to-disease-progression, and survival. Most importantly, all these results are statistically significant!
We showed that our laboratory’s published discoveries went on to become practice-changing in cancer medicine, from the first description of 2-CDA in Hairy Cell Leukemia (the curative therapy used around the world) to the discovery of the Cytoxan plus Fludarabine doublet, the most widely used treatment for patients with CLL (Nagourney. Br J Cancer 1993).
We were the first to describe Trastuzumab plus Vinorelbine in HER2 breast cancer (Nagourney Proc SABCS, 1999), also now used worldwide. Additionally, our discovery of cisplatin plus gemcitabine changed the worldwide management of breast, ovarian, uterine and bladder cancers, among others.
Our ground-breaking use of the EVA/PCD™ to select “1st-line” therapy in metastatic lung cancer (Nagourney. Anticancer Res. 2012) provided the best time to progression and survival ever reported at the time of its publication, with some survivors out 15 years.
Now with a growing interest in this field, some of the world’s most prestigious institutions are attempting to recreate our results.
The problem: they are using artificial cancer cell growth conditions to create three-dimensional cultures known as “3-D organoids” and suggesting, without evidence, that their tests can accurately predict cancer patient outcomes.
Like the old movie adage “Coming to a theater near you!”, your cancer doctor will soon tell you “We do that too”. Don’t be fooled.
Relying on needle biopsies and tiny specimens, these investigators are forced to grow cancer cells to expand the tumor cell numbers. While this provides researchers plenty of cells, making for lots of fun research, it irreversibly changes the tumor behavior, taking the cancer cells from their natural state to one of artificial expansion.
These cultures no longer reflect the cancer that the patients are confronting, but instead a new life form, a laboratory invention: the 3-D organoid. These doctors will soon provide the world with the cure of the “3-D organoid” Nobel-prize worthy, no doubt!
What is missing is the natural environment of the cancer cells; what we call the cancer cell microenvironment.
This can only be recreated by taking tumor cells out of body and placing them directly in the culture environment. No propagation, no expansion, no growth factors, no artificial matrix, and no feeder layers, just your tumor cells – plain and simple.
I am now genuinely concerned that a new generation of investigators, suddenly enamored with chemosensitivity testing, are quite simply doing it wrong.
This not only runs the risk of erroneous information for patients with profound adverse clinical implications (giving cancer patients the wrong drug or combination), but it also squanders the patient’s best and often only chance to do this right.
Moreover, as many of these studies will likely fail to accurately predict clinical response and survival, once clinically tested, these failures will sour the medical community on this extraordinarily important field.
Cancer patients need clinical care that is designed to meet their individual needs. Patients should not be unwitting guinea pigs for institutions that employ techniques that expand or amplify their cancer cell cultures for the purpose of conducting interesting experiments.
Unproven technologies should not be applied clinically until they have been shown to actually work.
Our AACR presentation concluded with an outline of several simple ways to establish whether any of these new drug sensitivity tests will work.
1. Do the “in vitro” results accurately reproduce the known activities of drugs currently in use today? That is, do drugs like corticosteroids used in childhood leukemia work better in childhood leukemia samples than in lung cancer samples, etc. Yes, or no? Is Taxol more active in breast than colon? Yes, or no?
2. Have they taken the trouble to show that test tube “sensitive” results (drugs found active in vitro and recommended for the patient treatment) actually predict a patient’s clinical response? Yes, or no?
3. Have they established performance characteristics like sensitivity, specificity, and predictive accuracy to provide statistical evidence of their platform’s clinical utility? Basically, “Does your test work?” Yes, or no?
If your doctor can show that their technique works, use it. But, if these tests have not been proven, then you will miss your one opportunity to get the right treatment.
You never have a second chance at first-line chemotherapy, but it is first-line chemotherapy that provides the greatest chance of cure.
Our EVA/PCD™ laboratory tests conducted in over 10,000 cancer patients with patient survivals reported in the peer-reviewed literature have been proven to work. Enough said!