CHEMOSENSITIVITY TESTING – PATIENT INFORMATION
Chemosensitivity testing of circulating tumour cells (CTCs) is a diagnostic tool that enables
individualised tailoring of cancer treatment (1). Chemosensitivity testing involves exposing
cultures of CTCs to each available cancer therapy agent and then analysing the cell’s
resistance or sensitivity to the treatment. The pathologist can observe sensitivity to treatment
by calculating the extent to which a chemotherapy agent induces destruction of cultured cells
(2). The pathologist can also observe resistant mechanisms present in the culture of CTCs by
observing the extent to which the cells maintain an active cycle despite exposure to the agent
(2). Recent studies that clarify the prospect of individualised cancer treatment through
chemosensitivity testing all affirm the importance of testing resistant mechanisms in cells of
tumour initiating capacity (TICs and CTCs) [1, 2]. These biomolecular markers on TICs and
CTCs may be responsible for the failure of primary therapy and therefore are a promising
target of individualised anti-cancer therapy [1, 3, 2, 4].
A major factor contributing to the possibility of individualised diagnosis through detection
and analysis of CTCs is simply the ease of sample collection and accessibility of the cells [1].
Traditionally, clinicians have had to obtain a tissue sample that needs preservation in
formalin and fixing in paraffin in order to analyse cancer cells [5]. Analysis of cancer cells
isolated from the peripheral circulation overcomes this hassle as well as providing a
continuous source of DNA, being free of selection bias, being instantaneous, less expensive
and far less invasive than a biopsy surgically removed from a solid tumour [6, 7].
RGCC’S CHEMOSENSITIVITY TEST is an in vitro test which identifies the sensitivity
of an individual’s cancer cells to chemotherapy, monoclonal antibodies and biological
response modifiers. It provides a panel of treatment options with objective evidence of
efficacy for the individual patient, from which the best treatment plan can then be selected.
The following agents are tested:
1. Chemotherapy drugs
5FU, ACNU, BCNU, Bendamustin, Bleomycin, Capecitabine, Carboplatin, CCNU, Cisplatin,
Cyclophosphamide, Dacarbazine, Dactinomycin, Daunorubicin, Docetaxel, Doxorubicin, Epirubicin,
Estramustin, Etoposide, Floxuridine, Gemcitabine, Idarubicin, Ifosphamide, Irinotecan, Liposomal
Doxorubicin, Melphalan, Methotrexate, Mitomycin, Mitoxantrone, Oxaliplatin, Paclitaxel, Pemetrexed,
Procarbazine, Ralitrexed, Temozolomide, Topotecan, Treosulfan, Trophosphamide, Uracil-Tegafur,
Vinblastine, Vincristine, Vinorelbine.
2. Targeted agents (growing all the time) including monoclonal antibodies and small
inhibiting molecules
Anastrozole, Bevacizumab, Bortezomib, Cetuximab, Coxibs, Imatinib mesylate, Leprolide,
Monteleucast, mTOR inhibitors, Raloxifen, Rituximab, Sorafenib and Sunitinib, Suramin sulphate,
Tamoxifen, Transtuzumab. Also Thalidomide (anti-angiogenesis and promotion of apoptosis).
Signalling pathways are checked for mutations downstream
3. Immunological modifiers
Cortisol, IFN, IL-2,
4. Biological Modifiers
Inhibitors of mechanisms of resistance: 5-Azacytidine, Disulfiram, Ketoconazole, Verapamil,
A genetic profile of the CTCs is given, with further potentially relevant targets eg NFκβ. Also
hormone receptor status and Heat shock proteins (HSP 27, HSP 90 and HSP 72).
Pharmacogenomics is also included for agents such as 5FU.
5. Natural / Complementary agents:
Acai berry, Acemannan, AHCC-Active Hexose Correlated Compound, Aloe vera extract, Amygdalin
(B17), Annonaceous acetogenins (paw paw), Ascorbic Acid, Astragalus complex, Avemar Pulvis,
Burdock complex, Caesium chloride, Co enzyme Q10, Cruciferous, C-Statin, Curcumin (turmeric),
CV247, Dim Avail, Echinea Premium Blend, Ellagic acid, Ganoderma, Grape Seed Supreme, Green
tea extract, Hydrogen Peroxide, Indol-3-carbinol, Intenzyme, IP6, Larrea, Lycopene, Maitake,
Mistletoe, N-acetyl-cysteine, New PME, Oncoflex, OPC, Pancreatic enzymes, PME, Poly-MVA,
Prolamine 1, Quercetin, Salvestrol, Selenium, Sodium Bicarbonate, Super Artemisinine, Superoxide
Dismutase, Thymex, Ukrain, Ultraretinol Plus, Uncaria tomentosa (samento),Vitamin E (tocopherol),
Vitanox.
Sample requirements:
The sample requirements are as follows:
a) For metastatic disease (circulating tumour cells must be present for this) - a 15 – 20ml
perhipheral (whole) blood sample is required. If there are no CTCs in a blood sample sent for
chemosensitivity testing, then the test will be charged as a screening test for CTCs.
b) For primary or localised disease eg stage 1 disease, brain tumours, tumours that don’t
metastasize - a tumour sample of approx 500mg is required.
Please call the office on 0117 317 1460 or email info@rgcc-europe-nw.com for further
information. We will put you in touch with a doctor in your area who offers these tests
privately.
Chemosensitivity testing by transcriptional profiling is one method of chemosensitivity testing. It goes without
saying that this type of testing will never predict in vivo response to treatment with 100% accuracy and there are
a number of reasons for this eg the role of the tumour microenvironment in drug resistance, pharmacokinetics
and pharmacodynamics in chemotherapy response, and post-translational mechanisms of drug resistance are not
directly measured with DNA microarrays. However, the clinical evidence for this type of ‘guided’ treatment
approach is growing. There are also good clinical results coming out of the clinics worldwide now using the test.
Audited figures from RGCC, collected from a number of clinics 2 months after the tests, have shown a
percentage of greater than 70% of patients either remaining stable or experiencing a degree of remission (some
complete) following treatments guided by the test results. All of these patients were in stage IV disease ie an
advanced stage.
Oncologists in the UK are bound by NICE guidelines and are under no obligation to provide treatments based
on these test results. This information is therefore intended for personal use, to open up options to people with
cancer, help them with their treatment decisions, and provide information about complementary and supportive
approaches relevant for their individual disease.
References:
1.
2.
3.
4.
5.
6.
7.
Yu, S.R., et al., Circulating tumor cells and individualized chemotherapy. Chin J Cancer, 2009. 28(11): p. 1225-32.
Morrison, B.J., et al., Future use of mitocans against tumour-initiating cells? Mol Nutr Food Res, 2009. 53(1): p. 147-53.
Zhou, B.B., et al., Tumour-initiating cells: challenges and opportunities for anticancer drug discovery. Nat Rev Drug Discov,
2009. 8(10): p. 806-23.
Ross, J.S., Breast cancer biomarkers and HER2 testing after 10 years of anti-HER2 therapy. Drug News Perspect, 2009. 22(2): p.
93-106.
Georg, L., et al., Circulating Tumor Cells in Gastrointestinal Malignancies: Current Techniques and Clinical Implications.
Journal of Oncology, 2009. 2010.
Panteleakou, Z., et al., Detection of circulating tumor cells in prostate cancer patients: methodological pitfalls and clinical
relevance. Mol Med, 2009. 15(3-4): p. 101-14.
NCI. Executive Summary of the Tumour Stem Cell & Self-Renewal Genes Think Tank. 2009 [cited 12 December 2009];
Available from: http://dcb.nci.nih.gov/thinktank/Executive_Summary_of_the_Tumor_Stem_Cell.cfm
Acknowledgement – for their contribution to the above text and references
Fluhrer, JG MBBS,FACNEM; Fluhrer, JE BSc (cand ) Biochemistry and
Molecular BiologyEmail: joachim@doctorfluhrer.com.au
© Copyright Fluhrer, JE and Fluhrer JG, April 2010