Prostate Cancer Lab #30: Using Functional Profiling to Predict Drug Response (Dr. Robert Nagourney)
Channel: Cancer Patient Lab
Date: 2023-07-07

October 19, 2022
Discussion forum: https://community.cancerpatientlab.org/home

Full transcript: https://cancerhackerlab.com/prostate-cancer-lab-30-using-functional-profiling-predict-drug-response-dr-robert-nagourney/

“The proper study of human tumors is human tumors.

“We must have the humility to recognize that cancer biology is demonstrably more complex than even our best scientists’ capabilities. This is an extremely complex interacting system with lots of moving parts… If we’re going to fix this, we have to listen carefully to what the tumor is telling us.

“Moving from genomics, transcriptomics, and proteomics to phenotypic metabolomics, the future will be bright.” - Dr. Robert Nagourney

Meeting Summary
Advanced cancer patients face complex treatment decisions. Screening drug options by putting the drugs on tumor tissue (functional testing) is a seemingly obvious way to get insights on what might and might not work. Drug combinations, dosing options, and random batches of FDA-approved drugs can be run through a functional testing process, often uncovering novel insights. Most clinicians are skeptical that there is any information to be gained from “ex vivo” (outside the body) tests. Advanced cancer patients are looking for any edge that can help guide them to a treatment.
Robert Nagourney, MD, is uniquely qualified to provide insights on the value of functional testing. He is a rare artisan in the medical field: an experienced physician treating patients who also runs a lab to guide treatment decisions, The Nagourney Cancer Institute. He bridges from testing to treatment, from pathology to oncology. Over the last 2 decades he pioneered functional testing as a means to predict which chemotherapies and drug combinations will be effective for patients. He helps patients who fit a profile - those with advanced disease and easy access to fresh tumor tissue. He guides their personalized care based on his extensive experience, using functional testing and recently metabolomics (analysis of how cells get energy).

How should we think about diagnosing and treating cancer?
To help advanced cancer patients make complex decisions about which treatments will work, one must listen carefully to what the tumor is telling us. Most advanced cancer patients get genomic sequencing which identifies unique biomarkers for a patient. To hit a biomarker target, you need confidence that the treatment will work. Cancer is not a gene, mutation, amplification, or a fusion. Cancer is a cell that has advantages that allow it to do what it’s doing to you. All it wants to do is stay alive - we’re trying to kill it.

Is therapy screening using functional testing worthwhile?
The Nagourney Cancer Institute/Rational Therapeutics has conducted a meta-analysis of clinical outcomes in peer-reviewed literature for over 2500 patients with solid tumors they have treated. It shows that their predictive therapy recommendations have provided higher reductions in the tumor burden (over 2x) and higher one-year survival (1.4x).

The information and opinions expressed on this website or platform, or during discussions and presentations (both verbal and written) are not intended as health care recommendations or medical advice by Cancer Patient Lab/Prostate Cancer Lab, its principals, presenters, participants, or representatives for any medical treatment, product, or course of action. You should always consult a doctor about your specific situation before pursuing any health care program, treatment, product or other course of action that might affect your health.

00:00:00 Meeting Intro
00:02:57 Presentation
00:05:57 Some Perspective: Cancer in 2022
00:07:19 Assay Endpoints - The Great Divide
00:06:45 The Task
00:08:22 Functional Profiling - Paradigm #1
00:09:02 B-Cell Leukemia  Saline Exposed
00:10:42 Dexamethasone in Childhood ALL
00:11:13 2 Chlorodeoxyadenosine (2-CDA)
00:13:56 Functional Profiling - Paradigm #2
00:14:33 Tumor Biology as Tumor Ecology
00:17:52 Subculturing...
00:18:32 Cancer Cell Response
00:19:17 We Do Not Create Human Cancers, We Observe Human Cancers
00:20:27 Your Cancer On Drugs
00:22:18 Gemcitabine (dfdc)
00:23:23 Gemcitabine Synergy in Solid Tumors
00:24:13 Gemcitabine plus Cisplatin Repeating Doublet Therapy
00:25:53 Cisplatin/Gemcitabine in Breast Cancer
00:25:17 Phase II Trial of Gemcitabine plus Cisplatin Repeating Doublet Therapy
00:25:54 Cisplatin/Gemcitabine in Ovarian Cancer
00:26:14 Functional Analysis of Human Tumor Microspheroids for Selection of Chemotherapy
00:27:17 Assay Directed Phase II Trial in NSCLC
00:27:36 Platinum Resistance in Gynecologic Malignancies
00:28:38 Nagourney Cancer Institute/Rational Therapeutics
00:30:10 Prostate Cancer: Actionable Targets; DNA Damage Repair
00:36:26 Appropriately Conducted Human Tumor Primary Culture Analysis
00:36:52 METABOLOMICS
00:37:24 Metabolism
00:37:45 Mass Spectrometry Human Metabolomics
00:38:38 Metabolomic Analysis of Prostate Cancer Plasma
00:41:38 Wrap Up/Q&A