This study is a revolutionary method for screening patients with twice and/or thrice negative breast cancer (HER2-, ER-, PR-) responding and not responding to monotherapy and/or combination therapy with the drugs fluorouracil, carboplatin, paclitaxel, gemzar, docetaxel, doxorubicin, cyclophosphamide, herceptin

Core Protocol

1. Objectives & Hypotheses

The objectives of this retrospective, study are to:

• 1) To determine the spectral characteristics of the effect of the studied drugs on macromolecular aggregates in whole blood and/or single-core peripheral blood cells in patients with thrice-negative breast cancer and twice-negative breast cancer.
• 2) Identify biomarkers and spectral profiles associated with response.
• 3) To determine responders and non- responder profiles treated with fluorouracil, carboplatin, paclitaxel, gemzar, docetaxel, doxorubicin, cyclophosphamide, herceptin as single therapy and/or in combination with an immune check-point blockade antibody, using with the aim to:

1. Predict responders/non-responders before the onset of treatment
2. Provide guidance for development of new therapies for the non-responder group

Expected impacts

The result of this proposal is the development of reliable methods to improve the effectiveness of treatment and personalized medicine. These new methods simplify the clinical monitoring of the treatment of twice and thrice negative breast cancer and allow for detailed data analysis, which will stimulate the development of new treatment methods. These new techniques can be adapted to other pathologies.

This could have a highly beneficial impact on patient health through personalized therapy which would significantly decrease negative side effects. These methodologies could reduce the costs of clinical trials by at least 30% thanks to the reliability of the small-scale clinical data trials to which these methods are applied.

2. Background & Rationale, Significance of Selected Topic & Preliminary Data

Cancer treatment is the perfect example of wasteful one size fits all therapy as the ideal treatment requires personalized and constant monitoring of disease and other biomarkers. The genetic markers that most current therapies are based on lack clinical relevance, especially after several rounds of unresponsive therapy change the tumor microenviroment.

Cancer constantly evolves from bad to worse. This can be accelerated if the chosen treatment fails to stop its progression due to iatrogenic modification. The challenge we are facing is to identify and validate markers that are able to predict treatment efficacy in a fast and highly reliable fashion in order to avoid missing the therapeutic window or at least to prevent worsening of clinical condition due to inadequate treatment strategy.

A breakthrough approach for screening responders and non-responders to   treatment fluorouracil, oxaliplatin, xeloda, irinotecan, avstin (bevacizumab) as single therapy and/or in combination with anti-PD-1 immunotherapy in patients compared with microsatellite stable metastatic colorectal cancer and  microsatellite instable metastatic colorectal cancer

Core Protocol

1. Objectives & Hypotheses

The objectives of this retrospective, study are to:

• 1) Determine the spectral characteristics of study drugs on macromolecular assemblies in whole blood and / or PBMCs from patients with microsatellite stable metastatic colorectal cancer and microsatellite instable metastatic colorectal cancer
• 2) Identify biomarkers and spectral profiles associated with response.

To determine responders and non- responder profiles treated with fluorouracil, oxaliplatin, xeloda, irinotecan, avstin (bevacizumab) as single therapy and/or in combination with an immune check-point blockade antibody, using with the aim to:

1. Predict responders/non-responders before the onset of treatment
2. Provide guidance for development of new therapies for the non-responder group

Expected impacts

The outcome of this proposal is the development of robust methodologies for increased treatment efficacy and personalized medicine. These new methods simplify clinical monitoring of treatment for microsatellite stable metastatic colorectal cancer and microsatellite instable metastatic colorectal cancer and allow for detailed data analysis that will spur development of new therapies. These new methodologies could be adapted to other pathologies.

This could have a highly beneficial impact on patient health through personalized therapy which would significantly decrease negative side effects. These methodologies could reduce the costs of clinical trials by at least 30% thanks to the reliability of the small-scale clinical data trials to which these methods are applied.

2. Background & Rationale, Significance of Selected Topic & Preliminary Data

Cancer treatment is the perfect example of wasteful one size fits all therapy as the ideal treatment requires personalized and constant monitoring of disease and other biomarkers. The genetic markers that most current therapies are based on lack clinical relevance, especially after several rounds of unresponsive therapy change the tumor microenviroment.

Cancer constantly evolves from bad to worse. This can be accelerated if the chosen treatment fails to stop its progression due to iatrogenic modification. The challenge we are facing is to identify and validate markers that are able to predict treatment efficacy in a fast and highly reliable fashion in order to avoid missing the therapeutic window or at least to prevent worsening of clinical condition due to inadequate treatment strategy.