HUMAN PAPILLOMA VIRUS AS PREDICTOR OF CANCER PROGNOSIS

Methods of treating a head and neck cancer are disclosed. 1. A method of treating a subject having a squamous cell carcinoma of the head and neck (HNSCC) , comprising:acquiring knowledge that the subject is negative for the human papillomavirus (HPV−); andadministering to the subject a cyclin dependent kinase (CDK) inhibitor,thereby treating the HNSCC in the subject.2. The method of claim 1 , wherein the CDK inhibitor inhibits one or both of CDK4 or CDK6.3. The method of claim 1 , wherein the CDK inhibitor is LEE011 claim 1 , LY-2835219 or PD 0332991.4. The method of claim 1 , wherein the CDK inhibitor is LEE011.5. The method of claim 1 , wherein the CDK inhibitor is LY-2835219.6. The method of claim 1 , wherein the CDK inhibitor is PD 0332991.7. The method of claim 1 , wherein the CDK inhibitor is Indisulam claim 1 , AZD5438 claim 1 , SNS-032 claim 1 , SCH 727965 claim 1 , JNJ-7706621 claim 1 , indirubin or Seliciclib.8. The method of claim 1 , wherein the subject is HPV− and has a mutation in a cell cycle gene chosen from cyclin dependent kinase inhibitor 2A (CDKN2A) claim 1 , cyclin dependent kinase inhibitor 2B (CDKN2B) claim 1 , Cyclin E1 (CCNE1) claim 1 , Cyclin D1 (CCND1) claim 1 , Cyclin D2 (CCND2) claim 1 , Cyclin D3 (CCND3) claim 1 , cyclin dependent kinase 4 (CDK4) or cyclin dependent kinase 6 (CDK6) claim 1 , or a gene described in Table 1 or Table 4.9. The method of claim 1 , wherein the subject has one or more of:(i) a loss-of-function mutation in the CDKN2A gene;(ii) a gain-of-function mutation in the CCND1 gene;(iii) a mutation or a mutant polypeptide described in Table 1 or 4; or(iv) a mutant CDKN2A, CDKN2B or CCND1 polypeptide.10. The method of claim 1 , further comprising acquiring knowledge of whether the subject has a mutation in a cell cycle gene chosen from CDKN2A claim 1 , CDKN2B claim 1 , CCNE1 claim 1 , CCND1 claim 1 , CCND2 claim 1 , CCND3 claim 1 , CDK4 or CDK6 claim 1 , or a gene described in Table 1 or Table 4.11. The method of claim 10 ...

METHODS OF TREATING UROTHELIAL CARCINOMA

Methods and compositions for treating a urothelial and/or a micropapillary carcinoma, such as a micropapillary urothelial carcinoma are disclosed. 130.-. (canceled)31. A method of treating a subject having a urothelial carcinoma , comprising administering to the subject an effective amount of an agent that targets and/or inhibits HER2 , thereby treating the urothelial carcinoma.32. The method of claim 31 , wherein the urothelial carcinoma is a micropapillary urothelial carcinoma (MPUC).33. The method of claim 31 , further comprising identifying the subject claim 31 , or a cancer or tumor sample from the subject claim 31 , as having one or both of:(a) the presence or absence of an alteration in HER2; or(b) the presence or absence of a micropapillary histology.34. A method of treating a subject having a carcinoma claim 31 , comprising:acquiring knowledge of:(a) the presence of an alteration in HER2; and(b) the presence of a micropapillary histology in the subject, or a cancer or tumor sample from the subject; andadministering to the subject an effective amount of an agent that targets and/or inhibits HER2, wherein the carcinoma is chosen from a cancer of the urinary tract, bladder, or urothelial cells,thereby treating the carcinoma.35. The method of claim 34 , wherein the carcinoma does not have claim 34 , or is identified as not having claim 34 , a gene amplification or overexpression of HER2 or a HER2 gene product.36. The method of claim 34 , wherein the carcinoma comprises claim 34 , or is identified as having claim 34 , an alteration in HER2 that results in an increased activity of a HER2 gene product claim 34 , compared to a wild type activity of HER2.37. The method of claim 34 , wherein the alteration in HER2 is chosen from:(i) a substitution, a deletion or an insertion;(ii) an alteration in the extracellular domain of HER2;(iii) an alteration in domain II of HER2;(iv) a missense mutation;(v) a substitution at position 310 of HER2;(vi) a substitution of a serine ...

NOVEL KIF5B-RET FUSION MOLECULES AND USES THEREOF

Novel RET fusion molecules and uses are disclosed. In one embodiment, a KIF5B-RET fusion includes an in-frame fusion of an exon of KIF5B (e.g., one or more exons encoding a kinesin motor domain or a fragment thereof) and an exon of RET (e.g., one or more exons encoding a RET tyrosine kinase domain or a fragment thereof). For example, the KIF5B-RET fusion can include an in-frame fusion of at least exon 15 of KIF5B or a fragment thereof (e.g., exons 1-15 of KIF5B or a fragment thereof) with at least exon 12 of RET or a fragment thereof (e.g., exons 12-20 of RET or a fragment thereof). 1. A method of reducing an activity of a KIF5B-RET fusion comprising:optionally, acquiring knowledge of the presence of the KIF5B-RET fusion; andcontacting the KIF5B-RET fusion, or a KIF5B-RET-expressing cell, with an agent that inhibits an activity or expression of KIF5B-RET.2. The method of claim 1 , wherein the contacting step is effected in vitro.3. The method of claim 1 , wherein the contacting step is effected in cells in culture.4. The method of claim 1 , wherein the contacting step is effected in a subject.5. The method of claim 1 , wherein the contacting step is effected in an animal subject.6. A method of treating a subject having cancer claim 1 , comprising:acquiring knowledge of the presence of a KIF5B-RET fusion in said subject; andadministering to the subject an effective amount of an anti cancer agent, thereby treating cancer in the subject.7. The method of claim 6 , wherein said anti cancer agent is a kinase inhibitor.8. The method of claim 7 , wherein the kinase inhibitor is administered responsive to the determination of presence of the KIF5B-RET fusion in a tumor sample from said subject.9. The method of claim 6 , wherein said administration is administered responsive to acquiring knowledge or information of the presence of the KIF5B-RET fusion in said subject.10. The method of claim 6 , wherein said administration is administered responsive to acquiring knowledge or ...

SYSTEM AND METHOD FOR MANAGING GENOMIC INFORMATION

A system for managing genomic information includes a processor to collect and store biomarker data, receive and store patient-specific pathology information, generate a graph-based data structure of complex data elements arranged into a walkable graph representation that includes at least one of a disease alteration group association (DAGA) element representing a relationship between a disease and an alteration group (AG), at least one of a disease therapy association (DTA) element representing a relationship between a disease and a therapy for treating the disease, and a therapy genomic effect (TGE) element representing a relationship between a gene and a known effect of a therapy on the gene. The processor follows links in the walkable graph representation to determine at least one inferred path, generates inferential matches to actionable items based on an accumulated trust score of the at least one inferred path, and determines a treatment decision for a cancer patient. 1 collect biomarker data and store the biomarker data in the memory;', 'receive patient-specific pathology information relating to the cancer patient and storing the patient-specific pathology information in the memory;', at least one of a disease alteration group association (DAGA) element representing a relationship between a disease and an alteration group (AG) that defines a unique set of clinically relevant biomarker data;', 'at least one of a disease therapy association (DTA) element representing a relationship between a disease and a therapy for treating the disease; and', 'a therapy genomic effect (TGE) element representing a relationship between a gene and a known effect of a therapy on the gene;, 'generate a graph-based data structure comprising a plurality of complex data elements arranged by the system into a walkable graph representation that comprises, 'traverse the walkable graph representation by following links between biomarker data, patient-specific pathology information, DAGA ...

METHODS OF TREATING UROTHELIAL CARCINOMA

Methods and compositions for treating a urothelial and/or a micropapillary carcinoma, such as a micropapillary urothelial carcinoma are disclosed. 1. A method of treating a subject having , or is at risk of having , a micropapillary urothelial carcinoma (MPUC) , comprising administering to the subject an effective amount of an agent that inhibits HER2 , thereby treating the MPUC.3. The method of claim 1 , wherein the agent is administered responsive to a determination of the presence of the HER2 alteration claim 1 , the micropapillary histology claim 1 , or both claim 1 , in the subject claim 1 , or a cancer or tumor sample from the subject.4. The method of claim 1 , wherein the subject is a human having a cancer.5. The method of claim 1 , wherein the carcinoma is not claim 1 , or is identified as not being claim 1 , an ERBB2-amplified cancer or carcinoma.6. The method of claim 1 , wherein the subject does not have claim 1 , or is identified as not having claim 1 , an elevated level of a HER2 gene product.7. The method of claim 1 , wherein the carcinoma comprises claim 1 , or is identified as having claim 1 , an alteration in HER2 that results in an increased activity of a HER2 gene product claim 1 , compared to a wild type activity of HER2 claim 1 , (i) a substitution, a deletion or an insertion;', '(ii) the alteration is found in the extracellular domain of HER2;', '(iii) the alteration is found in domain II of human HER2;', '(iv) a missense mutation;', '(v) a substitution at residue 310 of HER2;', '(vi) a substitution of residue S310 to phenylanine or tyrosine of HER2; or', '(vii) a substitution at residue 157., 'wherein the alteration in HER2 is chosen from8. The method of claim 1 , wherein the subject is undergoing or has undergone a treatment with a non-HER2 therapeutic agent or therapeutic modality.9. The method of claim 8 , wherein the non-HER2 therapeutic agent or therapeutic modality comprises one or more of: methotrexate claim 8 , vinblastine claim 8 , ...

HUMAN PAPILLOMA VIRUS AS PREDICTOR OF CANCER PROGNOSIS

Methods of treating a head and neck cancer are disclosed. 120-. (canceled)21. A method of treating a subject having a squamous cell carcinoma of the head and neck (HNSCC) , comprising:acquiring knowledge that the subject is positive for the human papillomavirus (HPV+); andadministering to the subject an anti-cancer agent other than a CDK inhibitor, thereby treating the HNSCC in the subject.22. The method of claim 21 , wherein the anti-cancer agent is cisplatin claim 21 , cetuximab claim 21 , fluorouracil (5-FU) claim 21 , carboplatin claim 21 , or paclitaxel.23. The method of claim 21 , wherein the subject is HPV+ claim 21 , and has a mutation in a phosphoinositide-3-kinase claim 21 , catalytic claim 21 , alpha polypeptide (PIK3CA) gene claim 21 , a phosphatase and tensin homolog (PTEN) gene claim 21 , or a serine/threonine kinase 11 (STK11) gene.24. (canceled)25. The method of claim 21 , wherein the subject is administered an mTOR inhibitor claim 21 , a PI3K inhibitor claim 21 , a PI3K/mTOR inhibitor claim 21 , or a PI3K/Akt/mTOR inhibitor.26. The method of claim 25 , wherein the mTOR inhibitor is rapamycin or a rapamycin derivative claim 25 , resveratrol claim 25 , or everolimus.27. (canceled)28. The method of claim 25 , wherein the PI3K/mTOR inhibitor is BEZ235 claim 25 , BGT226 claim 25 , BKM120 claim 25 , LY294002 or wortmannin.29. (canceled)30. A kit for assessing a subject having a squamous cell carcinoma of the head and neck (HNSCC) claim 25 , containing methods for determining whether a subject is HPV+ or HPV− claim 25 , and to accordingly identify an appropriate therapeutic agent to treat the HNSCC;wherein said kit comprises at least one or more of the following detection agents:(i) one or more PCR primers for detecting an HPV in a sample from the subject;(ii) one or more probes for detecting an HPV in a sample from the subject;(iii) one or more antibodies for detecting an HPV protein in a sample from the subject.31. The kit of further comprising one or ...

System and method for managing genomic information

Various embodiments provide interfaces to access genomic testing information and incorporate it into daily physician practice. According to one aspect, a graph-based data model is used that may be used to organizes and revise precision medicine knowledge. In one example structure, gene states are abstracted into alteration groups, where alteration groups are built using reverse engineering actionable information and storing that information within the graph-based data structure. Volumes of genomic alterations and associated information (e.g., journal articles, clinical trial information, therapies, etc.) are analyzed and synthesized into actionable information items viewable on an alteration system in a graph-based data format. According to one embodiment, the system can be configured to focus practitioners on discrete portions of the alteration information on which they can act. According to other aspects, curated information is provided on the system to enable practitioners to make informed decisions regarding the implications of the presence of specific genomic alterations.

System and method for managing genomic information

Various embodiments provide interfaces to access genomic testing information and incorporate it into daily physician practice. According to one aspect, a graph-based data model is used that may be used to organizes and revise precision medicine knowledge. In one example structure, gene states are abstracted into alteration groups, where alteration groups are built using reverse engineering actionable information and storing that information within the graph-based data structure. Volumes of genomic alterations and associated information (e.g., journal articles, clinical trial information, therapies, etc.) are analyzed and synthesized into actionable information items viewable on an alteration system in a graph-based data format. According to one embodiment, the system can be configured to focus practitioners on discrete portions of the alteration information on which they can act. According to other aspects, curated information is provided on the system to enable practitioners to make informed decisions regarding the implications of the presence of specific genomic alterations.

NOVEL NTRK1 FUSION MOLECULES AND USES THEREOF

Novel NTRK1 fusion molecules, detection reagents, and uses and kits for evaluating, identifying, assessing and/or treating a subject having a cancer are disclosed. 151.-. (canceled)52. A method of treating a subject having a lung cancer , comprising:administering to the subject an effective amount of an NTRK1-kinase specific inhibitor,thereby treating the lung cancer in the subject.53. The method of claim 52 , wherein the NTRK1-kinase specific inhibitor is chosen from danusertib (PHA-739358) claim 52 , lestaurtinib (CEP-701) claim 52 , AZ-23 claim 52 , or ARRY-470.54. The method of either of claim 52 , wherein the NTRK1 kinase inhibitor is administered responsive to a determination of the presence of claim 52 , or requiring knowledge or information of the presence of claim 52 , an MPRIP-NTRK1 fusion in a tumor sample from said subject.5558.-. (canceled)59. The method of claim 52 , further comprising determining the presence of an MPRIP-NTRK1 fusion by sequencing.60. The method of claim 52 , wherein said lung cancer is chosen from: small cell lung cancer (SCLC) claim 52 , adenocarcinoma of the lung claim 52 , bronchogenic carcinoma claim 52 , or a combination thereof.61. The method of claim 52 , wherein the lung cancer is non-small cell lung cancer (NSCLC) or squamous cell carcinoma (SCC).62. The method of claim 52 , wherein the lung cancer is an adenocarcinoma of the lung.63. The method of claim 52 , wherein the lung cancer has no detectable altered level or activity in one or more of EGFR claim 52 , KRAS claim 52 , ALK claim 52 , ROS1 or RET.64. (canceled)65. The method of claim 52 , wherein the NTRK-1 kinase inhibitor is selected from antisense molecules claim 52 , ribozymes claim 52 , RNAi claim 52 , triple helix molecules that hybridize to a nucleic acid encoding the fusion claim 52 , or a transcription regulatory region that blocks or reduces mRNA expression of the MPRIP-NTRK1 fusion.66. The method of claim 52 , wherein the NTRK-1 kinase inhibitor is ...

HUMAN PAPILLOMA VIRUS AS PREDICTOR OF CANCER PROGNOSIS

Methods of treating a head and neck cancer are disclosed. 129-. (canceled)30. A method for generating a personalized cancer treatment report , comprising:acquiring a sample from a subject having a squamous cell carcinoma of the head and neck (HNSCC);determining whether the subject is HPV− or HPV+; (i) if the subject is HPV+, a mammalian target of rapamycin (mTOR) inhibitor, a phosphatidylinositol-3 kinase (PI3K) inhibitor, or a PI3K/mTOR inhibitor is selected as a treatment, or', '(ii) if the subject is HPV−, a CDK inhibitor is selected as a treatment; and, 'selecting a treatment based on whether the subject is HPV− or HPV+, whereingenerating the personalized cancer treatment report to memorialize the selected treatment.31. The method of claim 30 , wherein the cancer treatment report memorializes when the subject is tested for the presence of HPV.32. The method of claim 30 , wherein the cancer treatment report comprises one or more of the following:(i) information on the HPV status of the subject;(ii) information on prognosis, resistance, or potential therapeutic options;(iii) information on the likely effectiveness of a therapeutic option;(iv) the acceptability of a therapeutic option, or the advisability of applying the therapeutic option to the subject; or(v) information on the administration of a drug.33. The method of claim 30 , wherein the mTOR inhibitor is rapamycin claim 30 , a rapamycin derivative claim 30 , resveratrol claim 30 , or everolimus.34. The method of claim 33 , wherein the rapamycin derivative is 40-O-(2-hydroxyethyl) rapamycin claim 33 , 40-[3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate]-rapamycin claim 33 , 40-epi-(tetrazolyl)-rapamycin claim 33 , CCI779 claim 33 , or ABT578.35. The method of claim 30 , wherein the PI3K inhibitor is BKM120 claim 30 , LY294002 claim 30 , or wortmannin.36. The method of claim 30 , wherein the PI3K/mTOR inhibitor is BEZ235 claim 30 , BGT226 claim 30 , or XL765.37. The method of claim 30 , wherein the CDK ...

METHODS OF TREATING UROTHELIAL CARCINOMA

Methods and compositions for treating a urothelial and/or a micropapillary carcinoma, such as a micropapillary urothelial carcinoma are disclosed. 130-. (canceled)31. A method for selecting a treatment for a subject having a micropapillary carcinoma of the urinary tract , bladder , or urothelial cells , comprising: (i) an alteration in a HER2 gene that results in an increased activity of a HER2 gene product, compared to a wild type activity of a HER2 gene product; and/or', '(ii) an alteration in a HER2 gene or gene product, wherein the alteration is:', 'a substitution, a deletion or an insertion in a HER2 gene,', 'an alteration in the extracellular domain of a HER2 polypeptide,', 'an alteration in domain II of a HER2 polypeptide,', 'a missense mutation in a HER2 gene,', 'a substitution at position 310 of a HER2 polypeptide,', 'a substitution of a serine residue at position 310 of a HER2 polypeptide to a phenylalanine or tyrosine residue,', 'a substitution of an arginine residue at position 157 of a HER2 polypeptide to a tryptophan residue;', 'a substitution at position 157 of a HER2 polypeptide, or'}], '(a) detecting in a sample from the subject a HER2 alteration, wherein the HER2 alteration is(b) selecting a treatment for the micropapillary carcinoma of the urinary tract, bladder, or urothelial cells in the subject based, at least in part, on the detecting, wherein the selected treatment comprises one or more agents that inhibit a HER2 gene or gene product; and(c) generating a report indicating the selected treatment.32. The method of claim 31 , wherein the report further comprises an indication of the presence in the sample of the HER2 alteration and/or an identification of nucleotide values of the HER2 alteration.33. The method of claim 31 , wherein the report further comprises an indication of micropapillary histology of the micropapillary carcinoma of the urinary tract claim 31 , bladder claim 31 , or urothelial cells.34. The method of claim 32 , wherein the ...

Novel kif5b-ret fusion molecules and uses thereof

Novel RET fusion molecules and uses are disclosed.

SYSTEM AND METHOD FOR OUTCOME TRACKING AND ANALYSIS

A system for tracking and analyzing cancer treatment and outcome information includes a user interface (UI) component for allowing selection of an alteration, an affected gene, an affected pathway, a tumor type, and/or a treatment; a processor configured to receive treatment information and outcome information associated with a patient population; organize the treatment information and the outcome information into at least one tuple; and generate outcome summary information; and an analysis component configured to compare a current patient record for a current patient to existing treatment information for the patient population, identify similar patients in the patient population based on information in the current patient record, and filter a grouping of similar patients; the processor is further configured to display, on the UI component, the outcome summary information; enable navigation within the treatment and outcome information; and identify, based on the outcome information, an appropriate treatment for the current patient. 1a user interface (UI) component configured to present at least one selection element for one or more of an alteration, an affected gene, an affected pathway, a tumor type, or a treatment; receive treatment information and outcome information associated with a patient population from at least one user;', 'organize the treatment information and the outcome information into at least one tuple containing one or more of the alteration, the affected gene, the affected pathway, the tumor type, or the treatment;', 'store the at least one tuple in a database indexed to speed retrieval of outcome summary information; and', 'generate, from the database, the outcome summary information including course of treatment displays over time; and, 'at least one processor operatively connected to a memory, the at least one processor when executing is configured to compare a current patient record for a current patient to existing treatment information for ...

SYSTEM AND METHOD FOR MANAGING GENOMIC TESTING RESULTS

Various embodiments provide interfaces to access genomic testing information and incorporate it into daily physician practice. In some embodiments, presentation of genomic alteration data is simplified and/or coupled with contextual applications. Volumes of genomic alterations and associated information (e.g., journal articles, clinical trial information, therapies, etc.) are analyzed and synthesized into actionable information items viewable on an alteration system. According to one embodiment, the system can be configured to focus practitioners on discrete portions of the alteration information on which they can act. According to other aspects, curated information is provided on the system to enable practitioners to make informed decisions regarding the implications of the presence of specific genomic alterations. 1. A system for managing delivery of genomic testing information , the system comprising: ["access genomic testing results including at least one gene and alteration combination for a patient's cancer;", "analyze one or more of a tumor type, gene, and alteration for the patient's cancer, wherein analyzing includes identifying associated information items matching at least one of the tumor type, gene, and alteration for the patient's cancer; and", 'generate at least one genomic data structure including at least one tag, wherein the at least one tag is selectable to transition a user interface from the genomic data structure to an associated information display space including at least one associated information item describing information related to characteristics of the genomic data structure., 'at least one processor operatively connected to a memory, the at least one processor when executing is configured to2. The system according to claim 1 , further comprising a user interface component claim 1 , executed by the at least one processor claim 1 , configured to display the at least one genomic data structure within a user interface accessible over a ...

SYSTEM AND METHOD FOR OUTCOME TRACKING AND ANALYSIS

Provided are systems and methods for capturing outcome information associated with various cancer treatments. The system facilitates capture and analysis of cancer treatment information and associated outcome information. The treatment and outcome information can include genomic analysis and information on treatment of different cancers. The system can store and analyze any one or more of: tumor type, genomic alterations (e.g., genes and associated alterations, gene sequence mutations, alterations, amplifications, deletions, etc.), and treatment data (including, for example, treatments targeted to specific genes and/or genomic alterations). Users of the outcome system can supply and use the treatment and outcome information to facilitate diagnosis and therapy decisions. User interfaces within the system can be configured to allow users to easily locate outcome information associated with particular treatments of tumors having certain genomic alterations. 1. A system for tracking and analysis of cancer treatment and outcome information , the system comprising: receive treatment and outcome information associated with a patient from at least one user;', 'organize the treatment and the outcome information according to one or more of alteration, affected gene, affected pathway, tumor type, and treatment;', 'generate outcome summary information including course of treatment displays over time; and', 'communicate the outcome summary information to the at least one user., 'at least one processor operatively connected to a memory, the at least one processor when executing is configured to2. The system according to claim 1 , wherein the treatment information includes any one or more of drugs claim 1 , therapeutics claim 1 , named drugs claim 1 , named therapeutics claim 1 , drug cocktails claim 1 , drug combinations claim 1 , radiation claim 1 , and surgery.3. The system according to claim 1 , wherein the outcome information includes information regarding a status of a ...

NOVEL KIF5B-RET FUSION MOLECULES AND USES THEREOF

Novel RET fusion molecules and uses are disclosed. 1. A method of reducing an activity of a Kinesin Family Member 5B (KIF5B)-RET fusion polypeptide or a nucleic acid molecule encoding the KIF5B-RET fusion polypeptide , comprising:optionally, acquiring knowledge of the presence of the KIF5B-RET fusion polypeptide or a nucleic acid molecule encoding the KIF5B-RET fusion polypeptide; andcontacting the KIF5B-RET fusion polypeptide or a nucleic acid molecule encoding the KIF5B-RET fusion polypeptide, or a KIF5B-RET-expressing cell, with an agent that inhibits an activity or expression of KIF5B-RET.25.-. (canceled)6. A method of treating a subject having cancer , comprising:acquiring knowledge of the presence of a Kinesin Family Member 5B (KIF5B)-RET fusion polypeptide or a nucleic acid molecule encoding the KIF5B-RET fusion polypeptide in said subject; andadministering to the subject an effective amount of an anti-cancer agent, thereby treating cancer in the subject.7. The method of claim 6 , wherein said anti-cancer agent is a kinase inhibitor.8. The method of claim 7 , wherein the kinase inhibitor:(i) is administered responsive to the determination of presence of the KIF5B-RET fusion polypeptide or a nucleic acid molecule encoding the KIF5B-RET fusion polypeptide in a tumor sample from said subject;(ii) inhibits the expression of the nucleic acid encoding the KIF5B-RET fusion polypeptide;(iii) is selected from an antisense molecule, a ribozyme, an RNAi molecule, or a triple helix molecule, each of which hybridizes to a nucleic acid molecule encoding the KIF5B-RET fusion polypeptide, or a transcription regulatory region that blocks or reduces mRNA expression of the nucleic acid molecule encoding the KIF5B-RET fusion polypeptide; or(iv) is administered in combination with a second therapeutic agent or a different therapeutic modality.9. The method of claim 6 , wherein:(i) said administration is administered responsive to acquiring knowledge or information of the presence ...

HUMAN PAPILLOMA VIRUS AS PREDICTOR OF CANCER PROGNOSIS

Methods of treating a head and neck cancer are disclosed. 129-. (canceled)30. A method of treating a subject having a squamous cell carcinoma of the head and neck (HNSCC) , comprising:(a) acquiring knowledge that the subject is positive for human papillomavirus (HPV+); and(b) administering a mammalian target of rapamycin (mTOR) inhibitor, a phosphatidylinositol-3 kinase (PI3K) inhibitor, or a PI3K/mTOR inhibitor to the subject, thereby treating the HNSCC in the subject.31. The method of claim 30 , further comprising acquiring knowledge that the subject has a mutation in one or more genes in the PI3K pathway.32. The method of claim 31 , wherein the one or more genes in the PI3K pathway are selected from the group consisting of phosphoinositide-3-kinase claim 31 , catalytic claim 31 , alpha polypeptide (PIK3CA); phosphatase and tensin homolog (PTEN); and serine/threonine kinase 11 (STK11).33. The method of claim 32 , wherein the mutation is a mutation described in Table 1 or Table 4.34. The method of claim 33 , wherein:(a) the mutation is a mutation in a PIK3CA gene, wherein the mutation is an amplification of a PIK3CA gene and/or a mutation in a PIK3CA gene that results in an amino acid substitution in a PIK3CA protein selected from the group consisting of E542K, E545K, H1047L, and E726K;(b) the mutation is a mutation in a PTEN gene, wherein the mutation is a deletion in a PTEN gene or a mutation in a PTEN gene that results in a truncated PTEN protein; or(c) the mutation is a mutation in a STK11 gene that results in an amino acid substitution in a STK11 protein of P324L.35. The method of claim 30 , wherein the subject has a mutation in one or more genes in the PI3K pathway.36. The method of claim 35 , wherein the one or more genes in the PI3K pathway are selected from the group consisting of PIK3CA claim 35 , PTEN claim 35 , and STK11.37. The method of claim 36 , wherein the mutation is a mutation described in Table 1 or Table 4.38. The method of claim 37 , wherein:( ...

SYSTEM AND METHOD FOR MANAGING GENOMIC TESTING RESULTS

Various embodiments provide interfaces to access genomic testing information and incorporate it into daily physician practice. In some embodiments, presentation of genomic alteration data is simplified and/or coupled with contextual applications. Volumes of genomic alterations and associated information (e.g., journal articles, clinical trial information, therapies, etc.) are analyzed and synthesized into actionable information items viewable on an alteration system. According to one embodiment, the system can be configured to focus practitioners on discrete portions of the alteration information on which they can act. According to other aspects, curated information is provided on the system to enable practitioners to make informed decisions regarding the implications of the presence of specific genomic alterations.

NOVEL NTRK1 FUSION MOLECULES AND USES THEREOF

Novel NTRK1 fusion molecules, detection reagents, and uses and kits for evaluating, identifying, assessing and/or treating a subject having a cancer are disclosed. 1. (canceled)2. A detection reagent , comprising a nucleic acid molecule that is capable of hybridizing to a MPRIP-NTRK1 breakpoint within a target nucleic acid molecule , and a detectable label or affinity tag.35-. (canceled)6. The detection reagent of claim 2 , wherein the detection reagent is a bait suitable for solution phase hybridization and capture of the target nucleic acid molecule.714-. (canceled)15. A reaction mixture comprising:{'claim-ref': {'@idref': 'CLM-00002', 'claim 2'}, 'the detection reagent of ; and'}a target nucleic acid derived from a lung cancer.16. (canceled)17. The reaction mixture of claim 15 , wherein the detection reagent comprises a DNA molecule claim 15 , an RNA molecule or a mixed DNA/RNA molecule.1819-. (canceled)20. A method of making a reaction mixture comprising:{'claim-ref': {'@idref': 'CLM-00002', 'claim 2'}, 'combining the detection reagent of with a target nucleic acid derived from a lung cancer.'}2131-. (canceled)32. A method of treating a subject having a lung cancer claim 15 , comprising:selecting the subject for treatment based on knowledge of the presence of an MPRIP-NTRK1 fusion in said subject; andadministering to the subject an effective amount of an anti-cancer agent, thereby treating the lung cancer in the subject.33. The method of claim 32 , wherein said anti-cancer agent is a kinase inhibitor.3439-. (canceled)40. The method of claim 32 , wherein said lung cancer is a small cell lung cancer (SCLC) claim 32 , an adenocarcinoma of the lung claim 32 , a bronchogenic carcinoma claim 32 , or a combination thereof.41. The method of claim 40 , wherein the lung cancer is non-small cell lung cancer (NSCLC) or squamous cell carcinoma (SCC).42. The method of claim 40 , wherein the lung cancer is an adenocarcinoma of the lung.43. The method of claim 40 , wherein the ...

HUMAN PAPILLOMA VIRUS AS PREDICTOR OF CANCER PROGNOSIS

Methods of treating a head and neck cancer are disclosed. 129.-. (canceled)30. A method of treating a subject with a cyclin dependent kinase (CDK) inhibitor , wherein the subject has a squamous cell carcinoma of the head and neck (HNSCC) , and wherein the CDK inhibitor inhibits one or both of cyclin dependent kinase 4 (CDK4) or cyclin dependent kinase 6 (CDK6) , the method comprising the steps of: obtaining a biological sample from the subject; and', 'performing an assay on the biological sample to determine if the subject has a mutation in a cell-cycle gene; and, 'determining whether the subject has a mutation in a cell-cycle gene byif the subject has a mutation in a cell-cycle gene, then administering the CDK inhibitor to the subject.31. The method of claim 30 , wherein the cell-cycle gene is chosen from a cyclin dependent kinase inhibitor 2A (CDKN2A) gene claim 30 , a cyclin dependent kinase inhibitor 2B (CDKN2B) gene claim 30 , a Cyclin E1 (CCNE1) gene claim 30 , a Cyclin D1 (CCND1) gene claim 30 , a Cyclin D2 (CCND2) gene claim 30 , a Cyclin D3 (CCND3) gene claim 30 , a CDK4 gene claim 30 , a CDK6 gene claim 30 , or a gene described in Table 1 or Table 4.32. The method of claim 30 , wherein the subject has one or more of:(i) a loss-of-function mutation in a CDKN2A gene;(ii) a gain-of-function mutation in a CCND1 gene;(iii) a mutation or a mutant polypeptide described in Table 1 or 4; or(iv) a mutant CDKN2A, CDKN2B, or CCND1 polypeptide.33. The method of claim 30 , wherein the mutation in the cell-cycle gene is detected in a nucleic acid molecule by one or more of: sequencing claim 30 , a nucleic acid hybridization assay claim 30 , an amplification-based assay claim 30 , a PCR-RFLP assay claim 30 , real-time PCR claim 30 , screening analysis claim 30 , FISH claim 30 , spectral karyotyping claim 30 , MFISH claim 30 , comparative genomic hybridization claim 30 , in situ hybridization claim 30 , SSP claim 30 , HPLC claim 30 , or mass-spectrometric genotyping.34. ...

METHODS OF TREATING CHOLANGIOCARCINOMA

Methods and compositions for treating cholangiocarcinoma. 1. A method of treating a subject having a cholangiocarcinoma , comprising:administering to the subject an effective amount of a therapeutic agent that antagonizes or inhibits FGFR2 or NTRK1,thereby treating the subject.2. A method of treating a subject having a cholangiocarcinoma , comprising:administering to the subject an effective amount of a kinase inhibitor chosen from an inhibitor of Table 2,thereby treating the subject.3. The method of claim 1 , wherein said therapeutic agent is chosen from:a kinase inhibitor;a multi-specific kinase inhibitor;an FGF receptor inhibitor (e.g., a pan FGFR2 inhibitor);an antibody molecule against FGFR2; and/ora kinase inhibitor that is selective for FGFR2 or NTRK1.4. The method of claim 1 , wherein said therapeutic agent is chosen from: Regorafenib; Ponatinib; AZD-2171 (Cediranib); AZD-4547; BGJ398; BIBF1120; Brivanib; Dovitinib; ENMD-2076; JNJ 42756493; Masitinib; Lenvatinib; LY2874455; Pazopanib; PD-173955; R406; PD173074; Danusertib; Dovitinib Dilactic Acid; TSU-68; Tyrphostin AG 1296; MK-2461; Brivanib Alaninate; Lestaurtinib; PHA-848125; K252a; AZ-23; or Oxindole-3 claim 1 , or a combination thereof.5. The method of claim 1 , wherein said therapeutic agent is regorafenib or ponatinib.6. The method of claim 1 , wherein said therapeutic agent is an antibody molecule.7. The method of claim 1 , wherein the therapeutic agent is selected from antisense molecules claim 1 , ribozymes claim 1 , RNAi claim 1 , triple helix molecules that hybridize to a nucleic acid encoding the fusion claim 1 , or a transcription regulatory region that blocks or reduces mRNA expression of the fusion.8. The method of claim 2 , wherein the kinase inhibitor is chosen from:a kinase inhibitor;a multi-specific kinase inhibitor;an FGF receptor inhibitor (e.g., a pan FGFR2 inhibitor); and/ora kinase inhibitor that is selective for FGFR2 or NTRK1.9. The method of claim 2 , wherein the kinase inhibitor ...

HUMAN PAPILLOMA VIRUS AS PREDICTOR OF CANCER PROGNOSIS

Methods of treating a head and neck cancer are disclosed. 129.-. (canceled)30. A method of treating a subject having a squamous cell carcinoma of the head and neck (HNSCC) , the method comprising:acquiring knowledge that the subject has a mutation in a cell-cycle gene; andadministering to the subject a cyclin dependent kinase (CDK) inhibitor that inhibits one or both of cyclin dependent kinase 4 (CDK4) or cyclin dependent kinase 6 (CDK6),thereby treating the HNSCC in the subject.31. The method of claim 30 , wherein the cell-cycle gene is chosen from a cyclin dependent kinase inhibitor 2A (CDKN2A) gene claim 30 , a cyclin dependent kinase inhibitor 2B (CDKN2B) gene claim 30 , a Cyclin E1 (CCNE1) gene claim 30 , a Cyclin D1 (CCND1) gene claim 30 , a Cyclin D2 (CCND2) gene claim 30 , a Cyclin D3 (CCND3) gene claim 30 , a CDK4 gene claim 30 , or a CDK6 gene claim 30 , or a gene described in Table 1 or Table 4.32. The method of claim 30 , wherein the subject has one or more of:(i) a loss-of-function mutation in a CDKN2A gene;(ii) a gain-of-function mutation in a CCND1 gene;(iii) a mutation or a mutant polypeptide described in Table 1 or 4; or(iv) a mutant CDKN2A, CDKN2B, or CCND1 polypeptide.33. The method of claim 30 , wherein the mutation in the cell-cycle gene is detected in a nucleic acid molecule by one or more of: sequencing claim 30 , a nucleic acid hybridization assay claim 30 , an amplification-based assay claim 30 , a PCR-RFLP assay claim 30 , real-time PCR claim 30 , screening analysis claim 30 , FISH claim 30 , spectral karyotyping claim 30 , MFISH claim 30 , comparative genomic hybridization claim 30 , in situ hybridization claim 30 , SSP claim 30 , HPLC claim 30 , or mass-spectrometric genotyping.34. The method of claim 30 , wherein the knowledge that the subject has a mutation in a cell-cycle gene is obtained from a sample isolated from the subject claim 30 , wherein the sample is a blood sample claim 30 , a serum sample claim 30 , a urine sample claim 30 ...

Novel kif5b-ret fusion molecules and uses thereof

Novel RET fusion molecules and uses are disclosed. In one embodiment, a KIF5B-RET fusion includes an in-frame fusion of an exon of KIF5B (e.g., one more exons encoding a kinesin motor domain or a fragment thereof) and an exon of RET (e.g., one or more exons encoding a RET tyrosine kinase domain or a fragment thereof). For example, the KIF5B-RET fusion can include an in-frame fusion of at least exon 15 of KIF5B or a fragment thereof (e.g., exons 1-15 of KIF5B or a fragment thereof) with at least ex on 12 of RET or a fragment thereof (e.g., exons 12-20 5 of RET or a fragment thereof).

Methods of treating cholangiocarcinoma

Methods and compositions for treating cholangiocarcinoma.

Kif5b-ret fusion molecules and uses thereof

Novel RET fusion molecules and uses are disclosed. In one embodiment, a KIF5B-RET fusion includes an in-frame fusion of an exon of KIF5B (e.g., one more exons encoding a kinesin motor domain or a fragment thereof) and an exon of RET (e.g., one or more exons encoding a RET tyrosine kinase domain or a fragment thereof). For example, the KIF5B-RET fusion can include an in-frame fusion of at least exon 15 of KIF5B or a fragment thereof (e.g., exons 1-15 of KIF5B or a fragment thereof) with at least ex on 12 of RET or a fragment thereof (e.g., exons 12-20 5 of RET or a fragment thereof).

Methods of treating cholangiocarcinoma

Methods and compositions for treating cholangiocarcinoma comprising a fusion nucleic acid or a fusion polypeptide of an FGFR2 gene.

Methods of treating cholangiocarcinoma

Methods and compositions for treating cholangiocarcinoma.

Human papilloma virus as predictor of cancer prognosis

Methods of treating a head and neck cancer are disclosed.

Methods of treating urothelial carcinomas

Novel kif5b-ret fusion molecules and uses thereof

Methods of treating cholangiocarcinoma

Methods and compositions for treating cholangiocarcinoma.

Human papilloma virus as predictor of cancer prognosis

Methods of treating a head and neck cancer are disclosed.

Methods of treating cholangiocarcinoma

Methods and compositions for treating cholangiocarcinoma.

Methods of treating cholangiocarcinoma

Human papilloma virus as predictor of cancer prognosis

Use of an anti-cancer agent in the treatment of an HNSCC in a subject, wherein the anti-cancer agent is other than a CDK inhibitor, and wherein the subject has been identified as being positive for a human papillomavirus (HPV+).

Methods of treating cholangiocarcinoma

Methods and compositions for treating cholangiocarcinoma.

Methods of treating cholangiocarcinoma

Methods and compositions for treating cholangiocarcinoma.

System and method for outcome tracking and analysis

Provided are systems and methods for capturing outcome information associated with various cancer treatments. The system facilitates capture and analysis of cancer treatment information and associated outcome information. The treatment and outcome information can include genomic analysis and information on treatment of different cancers. The system can store and analyze any one or more of: tumor type, genomic alterations (e.g., genes and associated alterations, gene sequence mutations, alterations, amplifications, deletions, etc.), and treatment data (including, for example, treatments targeted to specific genes and/or genomic alterations). Users of the outcome system can supply and use the treatment and outcome information to facilitate diagnosis and therapy decisions. User interfaces within the system can be configured to allow users to easily locate outcome information associated with particular treatments of tumors having certain genomic alterations.

Methods of treating post-myeloproliferative neoplasms (mpns) and post-mpn acute myeloid leukemia

Methods and compositions for treating post-myeloproliferative neoplasm acute myeloid leukemia are disclosed.

Methods of treating cholangiocarcinoma

Methods and compositions for treating cholangiocarcinoma.

Kif5b-ret fusion molecules and uses thereof

Novel RET fusion molecules and uses are disclosed. In one embodiment, a KIF5B-RET fusion includes an in-frame fusion of an exon of KIF5B (e.g., one more exons encoding a kinesin motor domain or a fragment thereof) and an exon of RET (e.g., one or more exons encoding a RET tyrosine kinase domain or a fragment thereof). For example, the KIF5B-RET fusion can include an in-frame fusion of at least exon 15 of KIF5B or a fragment thereof (e.g., exons 1-15 of KIF5B or a fragment thereof) with at least ex on 12 of RET or a fragment thereof (e.g., exons 12-20 5 of RET or a fragment thereof).

Methods of treating urothelial carcinomas

Methods and compositions for treating a urothelial and/or a micropapillary carcinoma, such as a micropapillary urothelial carcinoma are disclosed. Also disclosed is the use of a HER2 inhibitor for treating a subject having a micropapillary urothelial carcinoma, wherein the carcinoma, or a sample from the carcinoma, is identified as having an alteration in HER2 and a micropapillary histology, wherein the alteration is a HER2 kinase activating mutation in the extracellular domain chosen from: (i) a substitution at residue 310 of HER2; or (ii) a substitution at residue 157 of HER2.

Methods of treating urothelial carcinomas

Methods of treating hematological malignancies

Methods and compositions for treating and detecting hematological malignancies are disclosed.

Methods of treating urothelial carcinomas

Methods and compositions for treating a urothelial and/or a micropapillary carcinoma, such as a micropapillary urothelial carcinoma are disclosed.

Human papilloma virus as predictor of cancer prognosis

Methods of treating a head and neck cancer are disclosed.

Methods of treating cholangiocarcinoma

Methods and compositions for treating cholangiocarcinoma.

System and method for managing genomic information

System and method for outcome tracking and analysis

Provided are systems and methods for capturing outcome information associated with various cancer treatments. The system facilitates capture and analysis of cancer treatment information and associated outcome information. The treatment and outcome information can include genomic analysis and information on treatment of different cancers. The system can store and analyze any one or more of: tumor type, genomic alterations (e.g., genes and associated alterations, gene sequence mutations, alterations, amplifications, deletions, etc.), and treatment data (including, for example, treatments targeted to specific genes and/or genomic alterations). Users of the outcome system can supply and use the treatment and outcome information to facilitate diagnosis and therapy decisions. User interfaces within the system can be configured to allow users to easily locate outcome information associated with particular treatments of tumors having certain genomic alterations.

Methods of treating head and neck cancer

Methods of treating a head and neck cancer are disclosed.

KIF5B-RET fusion molecules and uses thereof

Novel RET fusion molecules and uses are disclosed. In one embodiment, a KIF5B-RET fusion includes an in-frame fusion of an exon of KIF5B (e.g., one or more exons encoding a kinesin motor domain or a fragment thereof) and an exon of RET (e.g., one or more exons encoding a RET tyrosine kinase domain or a fragment thereof). For example, the KIF5B-RET fusion can include an in-frame fusion of at least exon 15 of KIF5B or a fragment thereof (e.g., exons 1-15 of KIF5B or a fragment thereof) with at least exon 12 of RET or a fragment thereof (e.g., exons 12-20 of RET or a fragment thereof).

Methods of treating urothelial carcinoma

Methods and compositions for treating a urothelial and/or a micropapillary carcinoma, such as a micropapillary urothelial carcinoma are disclosed.