The current disclosure provides for specific peptides, and derived ionization characteristics of the peptides, from the ALK, Ros, Ron, Ret, TS, and/or FGFR1 proteins that are particularly advantageous for quantifying the ALK, Ros, Ron, Ret, TS, and/or FGFR1 proteins directly in biological samples that have been fixed in formalin by the methods of Selected Reaction Monitoring (SRM) mass spectrometry, or as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed wherein the biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from the biological sample using the Liquid Tissue™ reagents and protocol and the ALK, Ros, Ron, Ret, TS, and/or FGFR1 proteins are quantitated in the Liquid Tissue™ sample by the method of SRM/MRM mass spectrometry, by quantitating in the protein sample at least one or more of the peptides described. These peptides can be quantitated if they reside in a modified or an unmodified form. An example of a modified form of an ALK, Ros, Ron, Ret, TS, and/or FGFR1 fragment peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.

Provided are immunostimulatory bacteria with genomes that are modified to, for example, reduce toxicity and improve the anti-tumor activity, such as by increasing accumulation in the tumor microenvironment, particularly in tumor-resident myeloid cells, improving resistance to complement inactivation, reducing immune cell death, promoting adaptive immunity, and enhancing T-cell function. Also provided are immunostimulatory bacteria for use as vaccines, and for delivery of mRNA. The immunostimulatory bacterium comprise genome modifications resulting in an increase in colonization of phagocytic cells, which delivers encoded therapeutic products to phagocytic cells, and permits, among other routes, systemic administration of the immunostimulatory bacteria. The increase in colonization of phagocytic cells also provides for use of immunostimulatory bacteria for direct tissue administration for use as vaccines.

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 for the disease, such as treatments that provide likely benefit or likely lack of benefit for the disease.

Embodiments of the disclosure encompass methods and compositions for treatment of cancer utilizing fibroblasts that have been modified to enhance their ability to deliver one or more anti-cancer agents to an individual in need thereof. In particular embodiments, the fibroblasts have been modified to express on or more chemokine receptors and/or have been exposed to hypoxia to enhance their ability to home to cancer cells. In specific cases the modified fibroblasts are engineered to encompass an oncolytic virus as a tumor inhibitory agent.

In some aspects, isolated transgenic cells (e.g., transgenic T cells) are provided that comprise or express a transgene and DHFR.sup.FS and/or TYMS.sup.SS. Methods for selecting transgeneic cells are also provided.

Methods of treating cancer using antisense based therapies including antisense oligonucleotides of si RNAs directed against DNA double-strand break repair proteins such as BRCA2 or RAD51 are provided. The antisense based therapies can be used alone, in tandem or in combination with other cancer therapies, in particular with therapies that lead to DNA damage, inhibition of DNA repair or inhibition of DNA synthesis, such as radiation, platinum drugs, alkylating agents, PARP inhibitors, or inhibitors of thymidylate synthase.

The present invention provides compositions and methods for combination therapy comprising administering to a patient in need thereof, drug-resistant immunotherapy, immune checkpoint inhibitors, and chemotherapy for the treatment of cancer.

The present invention relates to modified bacterial spores, and particularly, although not exclusively, to modified bacterial spores which comprise one or more heterologous genes, but without the introduction of antibiotic resistance genes. The invention extends to methods for producing such modified bacterial spores, vectors and kits for introducing heterologous genes in a spore.

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 for the disease, such as treatments that provide likely benefit or likely lack of benefit for the disease.

The present invention provides compositions and methods for combination therapy comprising administering to a patient in need thereof, drug-resistant immunotherapy, immune checkpoint inhibitors, and chemotherapy for the treatment of cancer.