+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Multicellular resistance: a paradigm for clinical resistance?

Multicellular resistance: a paradigm for clinical resistance?

Critical Reviews in Oncology/Hematology 36(2-3): 193-207

Research on resistance to cancer treatment was mainly focused for 20 years on multidrug resistance (MDR). No useful method of reversing MDR, suitable for clinical use, has yet emerged from this large quantity of work. The reason could be an inadequate evaluation of the target. When grown in spheroids, cancer cells exhibit a phenomenon known as 'multicellular resistance' (MCR). Tumours in patients seem to present the same characteristics. The mechanisms underlying MCR can be classified into two forms: contact resistance and resistance inherent in the spheroid structure. Mechanisms of MCR include: inhibition of apoptosis, high proportion of quiescent cells, modulation of protein expression (including topoisomerases and repair enzymes), potential permeability problems, presence of a hypoxic and necrotic centre and other possible mechanisms that remain to be discovered. A new therapeutic class of drugs is required to overcome MCR. Compounds, which are able to disrupt communication and binding between tumour cells and their microenvironment, seem to be able to circumvent MCR. Interesting results are obtained in vitro and in vivo in mice with specific antibodies or peptides recognised by cell binding proteins. Interestingly, these compounds also appear to be able to inhibit metastasis. Hyaluronidase has already been used with anticancer drugs in patients and was shown to increase drug potency. The explanation given is that it improves drug penetration into spheroids. We now hypothesise that hyaluronidase, in fact, decreases MCR and thus could be the first member of a new therapeutic class.

(PDF emailed within 0-6 h: $19.90)

Accession: 035349716

Download citation: RISBibTeXText

PMID: 11033306

DOI: 10.1016/s1040-8428(00)00086-x

Related references

Multicellular resistance: a new paradigm to explain aspects of acquired drug resistance of solid tumors. Cold Spring Harbor Symposia on Quantitative Biology 59: 661-672, 1994

Multicellular resistance to alkylating agents defines a new concept of drug resistance in cancer. Proceedings of the American Association for Cancer Research Annual Meeting 34(0): 269, 1993

Multicellular resistance to tirapazamine is due to restricted extravascular transport: a pharmacokinetic/pharmacodynamic study in HT29 multicellular layer cultures. Cancer Research 63(18): 5970-5977, 2003

E-cadherin increasing multidrug resistance protein 1 via hypoxia-inducible factor-1α contributes to multicellular resistance in colorectal cancer. Tumour Biology 37(1): 425-435, 2015

Multicellular resistance: another mechanism for multidrug resistance?. Bulletin du Cancer 85(9): 785-785, 1998

Multicellular resistance: another mechanisms of pleiotropic resistance?. Bulletin du Cancer 85(9): 785-793, 1998

Life stressors, resistance factors, and improved psychological functioning: an extension of the stress resistance paradigm. Journal of Personality and Social Psychology 58(5): 909-917, 1990

The relationship between quinolone exposures and resistance amplification is characterized by an inverted U: a new paradigm for optimizing pharmacodynamics to counterselect resistance. Antimicrobial Agents and ChemoTherapy 51(2): 744-747, 2006

Functional genomics to discover antibiotic resistance genes: The paradigm of resistance to colistin mediated by ethanolamine phosphotransferase in Shewanella algae MARS 14. International Journal of Antimicrobial Agents 46(6): 648-652, 2016

Modulation of multidrug resistance: a paradigm for translational clinical research. Oncology 13(5a): 183-187, 1999

Anticipating clinical resistance to target-directed agents : the BCR-ABL paradigm. Molecular Diagnosis & Therapy 10(2): 67-76, 2006

Clinical studies of drug resistance. I. Clinical study on drug resistance (from the bacteriological stand point methods of measuring resistance and the clinic. Kekkaku 36: 475-479, 1961

Antibiotic resistance - is resistance detected by surveillance relevant to predicting resistance in the clinical setting?. Current Opinion in Pharmacology 2(5): 487-492, 2002

A study on PAS-resistance; its relation to clinical symptoms and SM-resistance, the change of resistance in the course of treatment. Kekkaku 30(11): 643-647, 1955

Development and application of a genotypic AZT resistance assay: quantitative assessment of the resistance profile of clinical samples and the relative predictive ability of a resistance index. Journal of Acquired Immune Deficiency Syndromes 28(3): 211-220, 2001