Molecular profiling for cancer
AssigneeCaris MPI, Inc.
InventorsGargi BASU, David ARGUELLO, Rebecca FELDMAN, Xinan XIU, Zoran GATALICA
Life of this patent
Estimating the term…
Abstract
Provided herein are methods and systems of molecular profiling of diseases, such as cancer. In some embodiments, the molecular profiling can be used to identify treatments that have likely benefit for a cancer, such as treatments that were not initially identified as a treatment for the disease or not expected to be a treatment for a particular disease. The molecular profiling can be used to identify likely have lack of benefit for treating the cancer.
Claims160
A method of identifying one or more candidate treatment for a cancer in a subject in need thereof, comprising:
- (a) determining a molecular profile for a sample from the subject by assessing a panel of gene or gene products, wherein the panel of gene or gene products are assessed as indicated in Table 21, FIG. 33A or FIG. 33B;
- and
- (b) identifying one or more treatment that is beneficially associated with the molecular profile of the subject, and optionally one or more treatment associated with lack of benefit, according to the determining in (a) and one or more rules in Table 22, thereby identifying the one or more candidate treatment.
The method of any preceding claim, wherein the panel of gene or gene products comprises the androgen receptor (AR).
The method of any preceding claim, wherein the cancer comprises an acute lymphoblastic leukemia;
- acute myeloid leukemia;
- adrenocortical carcinoma;
- AIDS-related cancer;
- AIDS-related lymphoma;
- anal cancer;
- appendix cancer;
- astrocytomas;
- atypical teratoid/rhabdoid tumor;
- basal cell carcinoma;
- bladder cancer;
- brain stem glioma;
- brain tumor, brain stem glioma, central nervous system atypical teratoid/rhabdoid tumor, central nervous system embryonal tumors, astrocytomas, craniopharyngioma, ependymoblastoma, ependymoma, medulloblastoma, medulloepithelioma, pineal parenchymal tumors of intermediate differentiation, supratentorial primitive neuroectodermal tumors and pineoblastoma;
- breast cancer;
- bronchial tumors;
- Burkitt lymphoma;
- cancer of unknown primary site (CUP);
- carcinoid tumor;
- carcinoma of unknown primary site;
- central nervous system atypical teratoid/rhabdoid tumor;
- central nervous system embryonal tumors;
- cervical cancer;
- childhood cancers;
- chordoma;
- chronic lymphocytic leukemia;
- chronic myelogenous leukemia;
- chronic myeloproliferative disorders;
- colon cancer;
- colorectal cancer;
- craniopharyngioma;
- cutaneous T-cell lymphoma;
- endocrine pancreas islet cell tumors;
- endometrial cancer;
- ependymoblastoma;
- ependymoma;
- esophageal cancer;
- esthesioneuroblastoma;
- Ewing sarcoma;
- extracranial germ cell tumor;
- extragonadal germ cell tumor;
- extrahepatic bile duct cancer;
- gallbladder cancer;
- gastric (stomach) cancer;
- gastrointestinal carcinoid tumor;
- gastrointestinal stromal cell tumor;
- gastrointestinal stromal tumor (GIST);
- gestational trophoblastic tumor;
- glioma;
- hairy cell leukemia;
- head and neck cancer;
- heart cancer;
- Hodgkin lymphoma;
- hypopharyngeal cancer;
- intraocular melanoma;
- islet cell tumors;
- Kaposi sarcoma;
- kidney cancer;
- Langerhans cell histiocytosis;
- laryngeal cancer;
- lip cancer;
- liver cancer;
- malignant fibrous histiocytoma bone cancer;
- medulloblastoma;
- medulloepithelioma;
- melanoma;
- Merkel cell carcinoma;
- Merkel cell skin carcinoma;
- mesothelioma;
- metastatic squamous neck cancer with occult primary;
- mouth cancer;
- multiple endocrine neoplasia syndromes;
- multiple myeloma;
- multiple myeloma/plasma cell neoplasm;
- mycosis fungoides;
- myelodysplastic syndromes;
- myeloproliferative neoplasms;
- nasal cavity cancer;
- nasopharyngeal cancer;
- neuroblastoma;
- Non-Hodgkin lymphoma;
- nonmelanoma skin cancer;
- non-small cell lung cancer;
- oral cancer;
- oral cavity cancer;
- oropharyngeal cancer;
- osteosarcoma;
- other brain and spinal cord tumors;
- ovarian cancer;
- ovarian epithelial cancer;
- ovarian germ cell tumor;
- ovarian low malignant potential tumor;
- pancreatic cancer;
- papillomatosis;
- paranasal sinus cancer;
- parathyroid cancer;
- pelvic cancer;
- penile cancer;
- pharyngeal cancer;
- pineal parenchymal tumors of intermediate differentiation;
- pineoblastoma;
- pituitary tumor;
- plasma cell neoplasm/multiple myeloma;
- pleuropulmonary blastoma;
- primary central nervous system (CNS) lymphoma;
- primary hepatocellular liver cancer;
- prostate cancer;
- rectal cancer;
- renal cancer;
- renal cell (kidney) cancer;
- renal cell cancer;
- respiratory tract cancer;
- retinoblastoma;
- rhabdomyosarcoma;
- salivary gland cancer;
- Sezary syndrome;
- small cell lung cancer;
- small intestine cancer;
- soft tissue sarcoma;
- squamous cell carcinoma;
- squamous neck cancer;
- stomach (gastric) cancer;
- supratentorial primitive neuroectodermal tumors;
- T-cell lymphoma;
- testicular cancer;
- throat cancer;
- thymic carcinoma;
- thymoma;
- thyroid cancer;
- transitional cell cancer;
- transitional cell cancer of the renal pelvis and ureter;
- trophoblastic tumor;
- ureter cancer;
- urethral cancer;
- uterine cancer;
- uterine sarcoma;
- vaginal cancer;
- vulvar cancer;
- Waldenstrdm macroglobulinemia;
- or Wilm's tumor.
The method of any preceding claim, wherein the cancer comprises an acute myeloid leukemia (AML), breast carcinoma, cholangiocarcinoma, colorectal adenocarcinoma, extrahepatic bile duct adenocarcinoma, female genital tract malignancy, gastric adenocarcinoma, gastroesophageal adenocarcinoma, gastrointestinal stromal tumor (GIST), glioblastoma, head and neck squamous carcinoma, leukemia, liver hepatocellular carcinoma, low grade glioma, lung bronchioloalveolar carcinoma (BAC), non-small cell lung cancer (NSCLC), lung small cell cancer (SCLC), lymphoma, male genital tract malignancy, malignant solitary fibrous tumor of the pleura (MSFT), melanoma, multiple myeloma, neuroendocrine tumor, nodal diffuse large B-cell lymphoma, non epithelial ovarian cancer (non-EOC), ovarian surface epithelial carcinoma, pancreatic adenocarcinoma, pituitary carcinomas, oligodendroglioma, prostatic adenocarcinoma, retroperitoneal or peritoneal carcinoma, retroperitoneal or peritoneal sarcoma, small intestinal malignancy, soft tissue tumor, thymic carcinoma, thyroid carcinoma, or uveal melanoma.
The method of any preceding claim, wherein the cancer comprises a prostate, bladder, kidney, lung, breast, or liver cancer.
A method of identifying one or more candidate treatment for an ovarian cancer in a subject in need thereof, comprising:
- (a) determining a molecular profile for a sample from the subject by assessing a panel of gene or gene products, wherein the panel of gene or gene products are assessed as indicated in Table 7, FIG. 33C or FIG. 33D;
- and
- (b) identifying one or more treatment that is beneficially associated with the molecular profile of the subject, and optionally one or more treatment associated with lack of benefit, according to the determining in (a) and one or more rules in Table 8, thereby identifying the one or more candidate treatment.
A method of identifying one or more candidate treatment for a breast cancer in a subject in need thereof, comprising:
- (a) determining a molecular profile for a sample from the subject by assessing a panel of gene or gene products, wherein the panel of gene or gene products are assessed as indicated in Table 9, FIG. 33K or FIG. 33L;
- and
- (b) identifying one or more treatment that is beneficially associated with the molecular profile of the subject, and optionally one or more treatment associated with lack of benefit, according to the determining in (a) and one or more rules in Table 10, thereby identifying the one or more candidate treatment.
A method of identifying one or more candidate treatment for a skin cancer (melanoma) in a subject in need thereof, comprising:
- (a) determining a molecular profile for a sample from the subject by assessing a panel of gene or gene products, wherein the panel of gene or gene products are assessed as indicated in Table 11, FIG. 33E or FIG. 33F;
- and
- (b) identifying one or more treatment that is beneficially associated with the molecular profile of the subject, and optionally one or more treatment associated with lack of benefit, according to the determining in (a) and one or more rules in Table 12, thereby identifying the one or more candidate treatment.
A method of identifying one or more candidate treatment for a uveal melanoma cancer in a subject in need thereof, comprising:
- (a) determining a molecular profile for a sample from the subject by assessing a panel of gene or gene products, wherein the panel of gene or gene products are assessed as indicated in Table 13, FIG. 33G or FIG. 33H;
- and
- (b) identifying one or more treatment that is beneficially associated with the molecular profile of the subject, and optionally one or more treatment associated with lack of benefit, according to the determining in (a) and one or more rules in Table 14, thereby identifying the one or more candidate treatment.
A method of identifying one or more candidate treatment for a colorectal cancer in a subject in need thereof, comprising:
- (a) determining a molecular profile for a sample from the subject by assessing a panel of gene or gene products, wherein the panel of gene or gene products are assessed as indicated in Table 15, FIG. 33M or FIG. 33N;
- and
- (b) identifying one or more treatment that is beneficially associated with the molecular profile of the subject, and optionally one or more treatment associated with lack of benefit, according to the determining in (a) and one or more rules in Table 16, thereby identifying the one or more candidate treatment.
A method of identifying one or more candidate treatment for a lung cancer in a subject in need thereof, comprising:
- (a) determining a molecular profile for a sample from the subject by assessing a panel of gene or gene products, wherein the panel of gene or gene products are assessed as indicated in Table 17, FIG. 33I or FIG. 33J;
- and
- (b) identifying one or more treatment that is beneficially associated with the molecular profile of the subject, and optionally one or more treatment associated with lack of benefit, according to the determining in (a) and one or more rules in Table 18, thereby identifying the one or more candidate treatment.
A method of identifying one or more candidate treatment for a glioma brain cancer in a subject in need thereof, comprising:
- (a) determining a molecular profile for a sample from the subject by assessing a panel of gene or gene products, wherein the panel of gene or gene products are assessed as indicated in Table 21, FIG. 33O or FIG. 33P;
- and
- (b) identifying one or more treatment that is beneficially associated with the molecular profile of the subject, and optionally one or more treatment associated with lack of benefit, according to the determining in (a) and one or more rules in Table 19, thereby identifying the one or more candidate treatment.
A method of identifying one or more candidate treatment for a gastrointestinal stromal tumor (GIST) cancer in a subject in need thereof, comprising:
- (a) determining a molecular profile for a sample from the subject by assessing a panel of gene or gene products, wherein the panel of gene or gene products are assessed as indicated in Table 21;
- and
- (b) identifying one or more treatment that is beneficially associated with the molecular profile of the subject, and optionally one or more treatment associated with lack of benefit, according to the determining in (a) and one or more rules in Table 20, thereby identifying the one or more candidate treatment.
A method of identifying one or more candidate treatment for a cancer in a subject in need thereof, comprising:
- (a) determining a molecular profile for a sample from the subject by assessing a panel of gene or gene products, wherein the panel of gene or gene products are assessed using IHC for AR, cMET, EGFR (including H-score for NSCLC), ER, HER2, MGMT, PGP, PR, PTEN, RRM1, SPARCm, SPARCp, TLE3, TOPO1, TOP2A, TS, TUBB3;
- FISH or CISH for ALK, cMET, HER2, ROS1, TOP2A;
- Mutational Analysis of BRAF (e.g., Cobas® PCR), IDH2 (e.g., Sanger Sequencing), MGMT promoter methylation (e.g., by PyroSequencing), EGFR (e.g., fragment analysis to detect EGFRvIII);
- and/or Mutational Analysis (e.g., by Next-Generation Sequencing) of ABL1, AKT1, ALK, APC, ATM, BRAF, CDH1, CSF1R, CTNNB1, EGFR, ERBB2 (HER2), ERBB4, FBXW7, FGFR1, FGFR2, FLT3, GNA11, GNAQ, GNAS, HNF1A, HRAS, IDH1, JAK2, JAK3, KDR (VEGFR2), KIT, KRAS, MET, MLH1, MPL, NOTCH1, NPM1, NRAS, PDGFRA, PIK3CA, PTEN, PTPN11, RB1, RET, SMAD4, SMARCB1, SMO, STK11, TP53, VHL;
- and
- (b) identifying one or more treatment that is beneficially associated with the molecular profile of the subject, and optionally one or more treatment associated with lack of benefit, according to the determining in (a) and one or more rules in any of Tables 7-22, thereby identifying the one or more candidate treatment.
The method of any preceding claim, further comprising additional molecular profiling according to FIG. 33Q.
A method of identifying one or more candidate treatment for a prostate cancer in a subject in need thereof, comprising:
- (a) determining a molecular profile for a sample from the subject on a panel of gene or gene products, wherein the panel of gene or gene products comprises immunohistochemistry (IHC) of AR, MRP1, TOPO1, TLE3, EGFR, TS, PGP, TUBB3, RRM1, PTEN and/or MGMT;
- in situ hybridization (ISH) of EGFR and/or cMYC;
- and/or sequencing of TP53, PTEN, CTNNB1, PIK3CA, RB11, ATM, cMET, K/HRAS, ERBB4, ALK, BRAF and/or cKIT;
- and
- (b) identifying one or more treatment that is beneficially associated with the molecular profile of the subject, and optionally one or more treatment associated with lack of benefit, according to the determining in (a) and one or more rules in Table 22, thereby identifying the one or more candidate treatment.
A method of identifying one or more candidate treatment for a cancer in a subject in need thereof, comprising:
- (a) determining a molecular profile for a sample from the subject by sequencing a panel of gene or gene products, wherein the panel of gene or gene products comprises one or more gene in Table 24;
- and
- (b) identifying one or more treatment that is beneficially associated with the molecular profile of the subject, and optionally one or more treatment associated with lack of benefit, according to the determining in (a) and one or more rules in Table 25 or any of Tables 7-22, thereby identifying the one or more candidate treatment.
The method of any preceding claim, wherein identifying the one or more treatment that is beneficially associated with the molecular profile of the subject, and optionally the one or more treatment associated with lack of benefit, comprises:
- (a) correlating the molecular profile with the one or more rules, wherein the one or more rules comprise a mapping of treatments whose efficacy has been previously determined in individuals having cancers that have different levels of, overexpress, underexpress, and/or have mutations in one or more members of the panel of gene or gene products;
- and
- (b) identifying one or more treatment that is associated with treatment benefit based on the correlating in (a);
- and optionally (c) identifying one or more treatment that is associated with lack of treatment benefit based on the correlating in (a).
The method of any preceding claim, further comprising identifying one or more candidate clinical trial for the subject based on the molecular profiling.
A method of identifying one or more candidate clinical trial for a subject having a cancer, comprising:
- (a) determining a molecular profile for a sample from the subject on a panel of gene or gene products;
- and
- (b) identifying one or more clinical trial associated with the molecular profile of the subject according to the determining in (a) and one or more biomarker-clinical trial association rules, thereby identifying the one or more candidate clinical trial.
The method of any preceding claim, wherein the sample comprises formalin-fixed paraffin-embedded (FFPE) tissue, fixed tissue, core needle biopsy, fine needle aspirate, unstained slides, fresh frozen (FF) tissue, formalin samples, tissue comprised in a solution that preserves nucleic acid or protein molecules, and/or a bodily fluid sample.
The method of any preceding claim, wherein the molecular profile comprises one or more additional gene or gene product listed in Table 2, Table 6 or Table 25.
The method of any preceding claim, wherein the sample comprises cells from a solid tumor.
The method of any preceding claim, wherein the sample comprises a microvesicle population.
The method of any preceding claim, wherein a prioritized list of the one or more candidate treatment is identified.
The method of any preceding claim, wherein the one or more candidate treatment is selected from those listed in any of Tables 3-5, 7-22, 28, 29, 33, 36 or 37.
The method of any preceding claim, wherein the subject has not previously been treated with the one or more candidate treatment that is associated with treatment benefit.
The method of any preceding claim, wherein the cancer comprises a metastatic cancer.
The method of any preceding claim, wherein the cancer comprises a recurrent cancer.
The method of any preceding claim, wherein the cancer is refractory to a prior treatment.
The method of any preceding claim, wherein progression free survival (PFS) or disease free survival (DFS) for the subject is extended by administration of the one or more candidate treatment to the subject.
The method of any preceding claim, wherein the subject's lifespan is extended by administration of the one or more candidate treatment to the subject.
The method of any preceding claim, wherein the molecular profile is compared to the one or more rules using a computer.
A method of generating a molecular profiling report comprising preparing a report comprising results of the molecular profile determined by any preceding claim.
Use of a reagent in carrying out the method of any previous claim.
A computer medium comprising one or more rules from any of Tables 7, 9, 11, 13, 15, 17, 21 and Table 28.
Dependencies are inferred from the claim text.