Predictive method for characterizing the sensitivity of a tumour in response to a dna-breaking treatment

Abstract

A process for evaluating the response of a tumour to a DNA-breaking treatment using a sample of cells from said tumour, in which: (a) a cell sample is prepared from the cells taken from said tumour; (b) said cell sample is subjected to a DNA-breaking treatment characterized by a dose D, (c) the average number of nuclear foci obtained with a marker pH2AX at the observation times t (these average numbers being respectively called NpH2Ax(t)) is determined on said cell sample, said observation times t being the time t=0 min (called tO, state before administration of the dose D) and at least one observation time selected from t = t1, t2, t3 and t4 after administration of the dose D; (d) at least one parameter or score which makes it possible to characterize the response of the sample to said DNA-breaking treatment is determined using at least the average numbers NpH2Ax(t), and in which process t4 is a fixed value which represents the time for which the level of DNA breaks reaches its residual value, t3 is a fixed value which represents the time after which approximately 25% of the double-strand breaks (DSBs) are repaired in control cells from radioresistant patients, t2 is a fixed valuewhich represents the time after which approximately 50% of the DSBs are repaired in control cells from radioresistant patients, t1 is a fixed value which represents the time after which the number ofrecognized DSBs reaches its maximum in control cells from radioresistant patients.

Description

technical field [0001] The present invention relates to the field of medical radiotherapy, more particularly to the field of radiotherapy laboratory methods. The present invention relates to a novel predictive method of cellular, tissue and clinical radiosensitivity based on the determination and cross-checking of various cellular and enzymatic parameters and criteria applied to tumor response. More specifically, the present invention relates to predictive methods for characterizing the susceptibility of tumors in response to radiotherapeutic treatment of DNA fragmentation. Background technique [0002] Non-surgical anticancer treatments are generally aimed at inducing cell death of cancer cells: most of these treatments induce DNA breaks and subsequently induce apoptosis of these cells. This is especially true for tumor treatment using ionizing radiation (radiotherapy). However, methods for predicting tumor response to such antineoplastic treatments are few and not reliab...

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Problems solved by technology

However, individual radiosensitivity was not considered

[0045] Despite the extensive prior art, applicants have observed that these patents do not describe a method for quantifying tumor susceptibility to DNA fragmentation processing, which is suitable for quantitative evaluation of the effect of anticancer therapy, which can be used in any patient and any Types of treatments prone to inducing DSBs, especially for any type of ionizing radiation

Therefore, the problem of providing methods for predicting tumor sensitivity and predicting tumor control irrespective of the clinical parameters used is still not effectively addressed

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