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Submission declined on 14 December 2023 by
Xegma (
talk). Few sections are unsourced please add sources on it.
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Functional drug sensitivity testing (f-DST) is an in-vitro diagnostic test method in functional precision medicine..
[1] developed to personalize the choice among cytotoxic drugs and drug combinations for patients with an indication for systemic chemotherapy in specific cancer types.
[2]
[3]
[4] f-DST is performed by various in-vitro diagnostic methods which have in common to quantify reactions of individual patient-derived cancer tissue when exposed to cytotoxic drugs. As substrate, testing methods initially require live cancer tissue from an individual patient (metastases or primary tumor).
Bioptic samples containing live cancer tissue are processed to obtain the required type, histologic organization and number of carcinomatous cells, ie. isolated cells, cell clusters, organoids or tumoroids of defined sizes.
The processed cancer specimen, cell or organized cell aggregates, are then cultured in stem cell media to increase in number and expand into a sufficient number of testable cancer cell aggregates as required, depending on the used test model. [5]
After defined time periods of culture, often between 3 and 7 days, cell or organized cell aggregates are counted and transferred to drug screening arrays, where they are exposed to defined concentrations of the cytotoxic drugs or drug combinations in question.
Measurement methods and statistical analyses usually focus on cell/cell aggregate behaviour in vitro under exposure to the test drugs after defined periods of time.
In vitro reactions of those patient-derived cancer cell or cell aggregates following exposure to standardized cytotoxic drug concentrations over a specified time are then calculated based on positive and negative controls and/or to calibration curves obtained from reference populations. [6]
Cytotoxic sytemic chemotherapies are generally considered effective across larger patient populations on average [7], but are known to come with different individual and side effect profiles. Therapeutic choices are currently based on the individual patient's overall medical situation and potential side effect tolerability. However, individual responses to systemic chemotherapy is known to vary due to differences in tumor biology, genetic makeup, and other factors. [8] This variability can affect the therapeutic risk/benefit ratio.
f-DST methodology comprises three basic steps: Pre-analytical processing of cancerous tissue samples, cultivation of the testable cellular product (ie. tumoroids, organoids, cell clusters, single cells) and subsequent exposition to the clinically most important cytotoxic agents (5-FU, oxaliplatin, irinotecan, individually or in combinations (CAPOX, FOLFOX, FOLFIRI, FOLFOXIRI), as well as to other cytotoxic substances [9], [10]
f-DST provides information on an individual patient's tumoroids / organoids / cell cluster / cell vulnerabilities towards cytotoxic chemotherapies in vitro [11]
f-DST requires repeat, fresh cancerous tissue biopsy procedures, which is not standard of care in the routine diagnostic workup of solid tumor patients in all stages of the disease [12].
If organoids or tumoroids are cultured for the purpose of fDST, results start being available from between 14 to 21 days after the bioptic procedure [13].
Like other functional testing methods (e.g. antibiograms), none of the current f-DST methods claims to fully replicate the intricate interactions of tumor tissue within a patient's body. However, information obtained by f-DST is being clinically investigated regarding relevant endpoints such as progression free survival [14].
f-DST is an emerging in vitro diagnostic tool. It has the potential to shift the current average cytotoxic drug efficacy / side effects risk balance of classic systemic chemotherapies for which no individual biomarkers exist.
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Submission declined on 14 December 2023 by
Xegma (
talk). Few sections are unsourced please add sources on it.
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How to improve a draft
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This draft has been resubmitted and is currently awaiting re-review. |
Functional drug sensitivity testing (f-DST) is an in-vitro diagnostic test method in functional precision medicine..
[1] developed to personalize the choice among cytotoxic drugs and drug combinations for patients with an indication for systemic chemotherapy in specific cancer types.
[2]
[3]
[4] f-DST is performed by various in-vitro diagnostic methods which have in common to quantify reactions of individual patient-derived cancer tissue when exposed to cytotoxic drugs. As substrate, testing methods initially require live cancer tissue from an individual patient (metastases or primary tumor).
Bioptic samples containing live cancer tissue are processed to obtain the required type, histologic organization and number of carcinomatous cells, ie. isolated cells, cell clusters, organoids or tumoroids of defined sizes.
The processed cancer specimen, cell or organized cell aggregates, are then cultured in stem cell media to increase in number and expand into a sufficient number of testable cancer cell aggregates as required, depending on the used test model. [5]
After defined time periods of culture, often between 3 and 7 days, cell or organized cell aggregates are counted and transferred to drug screening arrays, where they are exposed to defined concentrations of the cytotoxic drugs or drug combinations in question.
Measurement methods and statistical analyses usually focus on cell/cell aggregate behaviour in vitro under exposure to the test drugs after defined periods of time.
In vitro reactions of those patient-derived cancer cell or cell aggregates following exposure to standardized cytotoxic drug concentrations over a specified time are then calculated based on positive and negative controls and/or to calibration curves obtained from reference populations. [6]
Cytotoxic sytemic chemotherapies are generally considered effective across larger patient populations on average [7], but are known to come with different individual and side effect profiles. Therapeutic choices are currently based on the individual patient's overall medical situation and potential side effect tolerability. However, individual responses to systemic chemotherapy is known to vary due to differences in tumor biology, genetic makeup, and other factors. [8] This variability can affect the therapeutic risk/benefit ratio.
f-DST methodology comprises three basic steps: Pre-analytical processing of cancerous tissue samples, cultivation of the testable cellular product (ie. tumoroids, organoids, cell clusters, single cells) and subsequent exposition to the clinically most important cytotoxic agents (5-FU, oxaliplatin, irinotecan, individually or in combinations (CAPOX, FOLFOX, FOLFIRI, FOLFOXIRI), as well as to other cytotoxic substances [9], [10]
f-DST provides information on an individual patient's tumoroids / organoids / cell cluster / cell vulnerabilities towards cytotoxic chemotherapies in vitro [11]
f-DST requires repeat, fresh cancerous tissue biopsy procedures, which is not standard of care in the routine diagnostic workup of solid tumor patients in all stages of the disease [12].
If organoids or tumoroids are cultured for the purpose of fDST, results start being available from between 14 to 21 days after the bioptic procedure [13].
Like other functional testing methods (e.g. antibiograms), none of the current f-DST methods claims to fully replicate the intricate interactions of tumor tissue within a patient's body. However, information obtained by f-DST is being clinically investigated regarding relevant endpoints such as progression free survival [14].
f-DST is an emerging in vitro diagnostic tool. It has the potential to shift the current average cytotoxic drug efficacy / side effects risk balance of classic systemic chemotherapies for which no individual biomarkers exist.