Publications on Selectivity, Co-Bodies and Cancer
The problems of cancer drive a search for more selective agents in diagnosis and treatment.
Known examples prove that cooperative binding increases both affinity and selectivity; and also modifies specificity if dissimilar ligand groups can act together. Yet these phenomena have attracted scant attention, so the papers listed here emphasise the prospects, including in relation to cancer, where novel specifities and high affinity will be needed for the next generation of therapeutic agents. Every cancer is unique, comprising multiple sub-clones each derived from a first malignant clone that was itself unique; concepts not adopted in current practice and which must be grasped if there is to be any progress.
Two different binding proteins are linked together flexibly such that both can act simultaneously on the same target.
Two proteins are linked in a co-body so that both bind at once.
Cancers are each unique, so full diagnosis or complete elimination require precisely-directed heteropolyvalent agents - co-bodies.
Cancer diagnosis and treatment demand precise selective power.
Discriminatory power ( = selective power or selectivity) is enhanced by using several different pieces of evidence to distinguish between similar objects or appearances, i.e, pattern recognition. This is equally true of histopathology, clinical medicine, biochemical analysis and daily life.
Selection requires recognition of multiple identifiers
Every individual patient's cancer is unique from the outset because the random mutations present are so many. An initiating (malignant-clone-defining) mutation set defines the cancer, permits absolute identification of all cancer cells and suggests a mode of attack by specific polyvalent agents.
Diagnosis and treatment must acknowledge that each cancer is unique
A non-technical description of cancer for non-specialist readers, though referring to research results.
What cancer is, why it is so difficult to treat, new developments and a view of the future.
First published on the web 2008 and updated periodically since then, the last significant changes November 2011.
Cancer is explained truthfully though without jargon.
People recognise or select things as a conscious activity, but the sense is extended by analogy to how molecules or cells 'choose' partners for binding or reaction. This paper explores what molecular structures or characteristics are preferred for these purposes, and the potential particularly with respect to diagnosis of disease and treatment of cancer. A link here is to the text of the lecture. The slides are presented separately through a link on a neighbouring web page.
Recognition is favoured by certain ligand properties.
Royal Society of Medicine, 29th November 2007, ‘Cell Signalling and Novel Cancer Therapeutics.' Joint Meeting of the Oncology Section of the Royal Society of Medicine and the British Association of Cancer Research.
Nucleid acid linkers are favoured for heteropolyvalent binding agents in cancer.
Artificial heteropolyvalency introduces a novel specificity (for the totality of epitopes) and demands a re-examination of our concepts, including about molecular flexibility.
Polyvalent binding enhances affinity, heteropolyvalent binding introduces new specificities
Antibody Fab fragments or similar binding entities may be combined artificially to give agents with novel, combined specificity, plus enhanced affinity and selective power.
Polyvalency increases affinity, selectivity and specificity
An oligonucleotide is attached to each protein and the linked, flexible molecule forms by hybridisation between chains.
Proteins are linked by hybridisation of nucleic acid chains