Abstract: The present invention provides methods for predicting or modeling a chemotherapy outcome for a given patient, to assist physicians in the selection of chemotherapeutic agents for individualized cancer treatment.

Abstract: The assays, methods, tools and systems discussed herein represent an improved and unified system for monitoring the progression of an individual patient malignancy. The assays, methods, tools and systems discussed herein represent an improved and unified system for monitoring and for identifying cellular and secreted markers, for screening cells to detect phenotypic and genotypic drift and for predicting chemotherapeutic response of patient tumor cells to at least one therapeutic agent. The assays, methods, tools and systems discussed herein also represent an improved and unified system for monitoring and for screening multiple pharmaceutical agents for efficacy and long term effect as to a specific patient.

Abstract: The present invention provides methods for individualizing chemotherapy, and particularly methods for individualizing neoadjuvant chemotherapy. The present invention provides methods for predicting a cancer patient's response to neoadjuvant chemotherapy, including assessing the probability of a positive response upon treatment with candidate agents prior to surgery. In various aspects, the invention involves culturing a monolayer of malignant cells from an explant of a patient's biopsy specimen, such as a transcutaneous biopsy-sized specimen, and testing the malignant cells for resistance or sensitivity to one or a plurality of candidate agents for neoadjuvant therapy. In other aspects, the invention provides methods for accurately scoring and interpreting such assays, and discloses in vitro chemoresponse results that are predictive of a patient's pathological complete response (pCR) upon receiving the corresponding treatment regimen.

Abstract: The present invention provides methods, systems, and kits for evaluating the sensitivity and/or resistance of tumor specimens to one or a combination of chemotherapeutic agents. Particularly, the invention provides malignant cell gene signatures that are predictive of a tumor's response to candidate chemotherapeutic regimens.

Abstract: The assays, methods, tools and systems discussed herein represent an improved and unified system for monitoring the progression of an individual patient malignancy. The assays, methods, tools and systems discussed herein represent an improved and unified system for monitoring and for identifying cellular and secreted markers, for screening cells to detect phenotypic and genotypic drift and for predicting chemotherapeutic response of patient tumor cells to at least one therapeutic agent. The assays, methods, tools and systems discussed herein also represent an improved and unified system for monitoring and for screening multiple pharmaceutical agents for efficacy and long term effect as to a specific patient.

Abstract: The present invention provides methods for individualizing chemotherapy, and particularly methods for individualizing neoadjuvant chemotherapy. The present invention provides methods for predicting a cancer patient's response to neoadjuvant chemotherapy, including assessing the probability of a positive response upon treatment with candidate agents prior to surgery. In various aspects, the invention involves culturing a monolayer of malignant cells from an explant of a patient's biopsy specimen, such as a transcutaneous biopsy-sized specimen, and testing the malignant cells for resistance or sensitivity to one or a plurality of candidate agents for neoadjuvant therapy. In other aspects, the invention provides methods for accurately scoring and interpreting such assays, and discloses in vitro chemoresponse results that are predictive of a patient's pathological complete response (pCR) upon receiving the corresponding treatment regimen.

Abstract: An improved system for assaying expression of various markers, factors or antigens on the cultured cells for diagnostic purposes and for using such expression to monitor the applicability of certain candidate therapeutic or chemotherapeutic agents and the progress of treatment with those agents.

Abstract: An improved system for screening a multiple of candidate therapeutic or chemotherapeutic agents for efficacy as to a specific patient, in which a tissue sample from the patient is harvested, cultured and separately exposed to a plurality of treatments and/or therapeutic agents for the purpose of objectively identifying the best treatment or agent for the particular patient. Specific method innovations such as tissue sample preparation techniques render this method practically as well as theoretically useful. By subjecting uniform samples of cells to a wide variety of active agents (and concentrations thereof), the most promising agent and concentration for treatment of a particular patient can be determined.

Abstract: An improved system for screening a multiple of candidate therapeutic or chemotherapeutic agents for efficacy as to a specific patient, in which a tissue sample from the patient is harvested, cultured and separately exposed to a plurality of treatments and/or therapeutic agents for the purpose of objectively identifying the best treatment or agent for the particular patient. Specific method innovations such as tissue sample preparation techniques render this method practically as well as theoretically useful. By subjecting uniform samples of cells to a wide variety of active agents (and concentrations thereof), the most promising agent and concentration for treatment of a particular patient can be determined.

Abstract: Methods are provided for accurately predicting efficacy of chemotherapeutic agents. Methods of the invention increase the positive predictive value of chemosensitivity assays by assessing both the ability of a chemotherapeutic to destroy cells and the genetic propensity of those cells for resistance. Results obtained using methods of the invention provide insight into the in vivo effectiveness of a therapeutic, and lead to more effective chemotherapeutic treatment.

Abstract: The present invention provides methods for predicting or modeling a chemotherapy outcome for a given patient The method produces chemoresponse data, and presents the chemoresponse data in a clinically meaningful context such that the data can be meaningfully interpreted and evaluated in a clinical context The method of the invention involves correlating in vitro chemoresponse results for a particular patient with historical treatment outcomes Where a population of historical outcomes are matched to the patient by one or more clinical variables and such outcomes are matched to a potential treatment by the in vitro efficacy of the agent received, a meaningful simulation of the potential treatment for the patient can be constructed Simulations, such as survival curves, for a plurality of potential treatments may be generated and compared to contrast the estimated outcomes for several potential treatments, thereby providing the information desirable to design an individualized treatment regimen.

Abstract: An improved method for preparing a cell culture is disclosed. The method includes culturing a multicellular tissue explant in the presence of growth medium that is substantially free of enzymes capable of digesting the explant and, subsequently, removing the explant at a predetermined time.

Abstract: The present invention provides methods for preparing drug response and/or resistance profiles for breast tumor specimens, or cells derived therefrom. The drug response and/or resistance profiles are useful for determining effective chemotherapeutic agents for treatment of the tumor or cell to thereby individualize patient therapy. In other aspects, the invention provides a method for identifying a pathway or gene expression signature indicative of a breast cancer cell's sensitivity to a chemotherapeutic agent, which is useful for identifying a population response rate, or patient sub-population likely to respond to the drug candidate.

Abstract: The present invention provides methods for preparing a gene expression profile of a breast cancer cell, tumor, or cell line, where the gene expression profile may be evaluated for one or more gene expression signatures indicative of multidrug resistance. The signature may be indicative of resistance to one or more chemotherapeutic agents selected from a Taxol (e.g., Docetaxel or Paclitaxel), an antibiotic (e.g., Doxorubicin or Epirubicin), an antimetabolite (e.g., Fluorouracil and/or Gemcitabine), and an alkylating agent (e.g., Cyclophosphamide). Generally, the gene expression profile contains the level of expression for a plurality of genes listed in FIGS. 3, 4, and/or 5. Gene expression profiles for evaluating multidrug resistance for ER positive and ER negative breast cancers are also provided.

Abstract: Methods are provided for accurately predicting efficacy of chemotherapeutic agents. Methods of the invention increase the positive predictive value of chemosensitivity assays by assessing both the ability of a chemotherapeutic to destroy cells and the genetic propensity of those cells for resistance. Results obtained using methods of the invention provide insight into the in vivo effectiveness of a therapeutic, and lead to more effective chemotherapeutic treatment.

Abstract: The present invention provides methods for individualizing therapy for cancer treatment, and particularly for evaluating a patient's responsiveness to one or more antifolate therapeutic agents prior to treatment with such agents. Particularly, the invention provides an in vitro chemoresponse assay for predicting a patient's response to an antifolate agent, such as pemetrexed or methotrexate.

Abstract: An improved system for screening a multiple of candidate therapeutic or chemotherapeutic agents for efficacy as to a specific patient, in which a tissue sample from the patient is harvested, cultured and separately exposed to a plurality of treatments and/or therapeutic agents for the purpose of objectively identifying the best treatment or agent for the particular patient. Specific method innovations such as tissue sample preparation techniques render this method practically as well as theoretically useful. By subjecting uniform samples of cells to a wide variety of active agents (and concentrations thereof), the most promising agent and concentration for treatment of a particular patient can be determined.

Abstract: The present invention provides methods, systems, and kits for evaluating the sensitivity and/or resistance of tumor specimens to one or a combination of chemotherapeutic agents. Particularly, the invention provides malignant cell gene signatures that are predictive of a tumor's response to candidate chemotherapeutic regimens.

Abstract: The present invention provides methods for individualizing chemotherapy for cancer treatment, and particularly for evaluating a patient's responsiveness to one or more epidermal growth factor receptor (EGFR) inhibitors prior to treatment with such agents. Particularly, the invention provides an in vitro chemoresponse assay for predicting a patient's response to a monoclonal EGFR antibody, such as cetuximab. The method generally comprises culturing malignant cells from a patient's specimen (e.g., biopsy specimen), contacting the cultured cells with a monoclonal EGFR antibody that is a candidate treatment for the patient, and evaluating the cultured cells for a response to the drug. In certain embodiments, monolayer(s) of malignant cells are cultured from explants prepared by mincing tumor tissue, and the cells of the monolayer are suspended and plated for chemosenstivity testing.

Abstract: Methods are provided for accurately predicting efficacy of chemotherapeutic agents. Methods of the invention increase the positive predictive value of chemosensitivity assays by assessing both the ability of a chemotherapeutic to destroy cells and the genetic propensity of those cells for resistance. Results obtained using methods of the invention provide insight into the in vivo effectiveness of a therapeutic, and lead to more effective chemotherapeutic treatment.