Derivatives of mDIVI-1 may be used to target and eliminate cancer stem cells. Disruption in the mitochondrial dynamics balance plays a role in cancer. Proteins involved in regulating mitochondrial dynamics represent potential targets for cancer treatment. Mitochondrial fission protein DRP1 is such a target. Derivatives of mDIVI-1 inhibit DRP1, and have demonstrated inhibition of tumorsphere forming capacity, migration and stemness-related signaling in breast cancer cells. These properties result from induction of mitochondrial oxidative stress and reduction of mitochondrial metabolism in the target cancer cells. The potency of an mDIVI-1 derivative may be dramatically increased through addition of at least one membrane-targeting signal and/or a mitochondria-targeting signal.

The invention provides compositions, formulations, and methods for treatment of malignancies via activation of an inflammatory response in the subject. Such compositions, formulations, and methods for are preferably used in conjunction with other therapies for the treatment and/or management of malignancies, e.g., chemotherapy and/or radiation. The invention also provides methods of monitoring immune activation in subjects with malignancies.

Provided herein are compositions including peptide or nucleic acids encoding peptides and related methods for the treatment of angiogenic conditions such as cancer, vascular disorders such as cardiovascular disorders, and infectious disease.

Provided herein are compositions including peptide or nucleic acids encoding peptides and related methods for the treatment of angiogenic conditions such as cancer, vascular disorders such as cardiovascular disorders, and infectious disease.

The present invention generally relates to artemisinin/dihydroartemisinin (DHA) derivatives, and their use for therapy, in particular cancer therapy. These tumor-homing artemisinin derivatives (THAD) comprise three moieties: an artemisinin/DHA or a derivative thereof, a heptamethine carbocyanine dye (HMCD) residue, and a linker that conjugates the HMCD dye residue to the artemisinin residue. The THAD include compounds wherein the linker is linked to one or two DHA residue(s) via one or more ether bonds, and wherein the linker is linked to two DHA residues via two bonds independently selected from ester, carbamate and thiocarbamate. The THAD of the invention provide improved growth inhibition of cancer cells. The present invention also relates to improved methods of cancer therapy wherein a THAD is administered to a cancer patient. In embodiments, one or more THAD may be co-administered in a coordinated administration schedule. Advantages of the THAD and their use include, among others, improved dose-response and/or efficacy. The invention also relates to new dyes, their drug conjugates, and processes of making them.

The present application discloses anti-NME antibodies and their use in treating or preventing diseases.

The present invention relates to methods for diagnosing, staging and treating cancer, in particular melanoma. In particular, the present invention provides methods for determining the stage/type of a cancerous disease, comprising detecting somatic alterations of the DNA of one or more disseminated cancer cells (DCCs), obtained after homing to a distant organ, such as lymph node; and determining the somatic evolution of the DCC(s) based on the detected somatic alterations, wherein the somatic evolution is indicative of the stage/type of the cancerous disease.

The present disclosure relates to novel sulfonylurea and sulfonyl thiourea compounds and related compounds and their use in treating a disease or condition responsive to modulation of cytokines such as IL-1β and IL-18, modulation of NLRP3 or inhibition of the activation of NLRP3 or related components of the inflammatory process.

Provided herein are bifunctional compounds with a moiety (e.g., lenalidomide, thalidomide) that is a binder of an E3 ubiquitin ligase (e.g., Cereblon) and another moiety (e.g., RA190) that is a binder of the ubiquitin receptor RPN13 to induce degradation of RPN13 and thereby inhibit proteasome function. Also provided are pharmaceutical compositions comprising the bifunctional compounds, and methods of treating and/or preventing diseases (e.g., proliferative diseases, cancers, benign neoplasms, pathological angiogenesis, inflammatory diseases, and autoimmune diseases). Provided also are methods of inducing the degradation of ubiquitin receptor RPN13 by administering a bifunctional compound or composition described herein, wherein one component of the bifunctional compound is a binder of an E3 ubiquitin ligase (e.g., lenalidomide, thalidomide) and another component of the compound is a binder of ubiquitin receptor RPN13 (e.g., RA190) in a subject.

Provided herein are bifunctional compounds with a moiety (e.g., lenalidomide, thalidomide) that is a binder of an E3 ubiquitin ligase (e.g., Cereblon) and another moiety (e.g., RA190) that is a binder of the ubiquitin receptor RPN13 to induce degradation of RPN13 and thereby inhibit proteasome function. Also provided are pharmaceutical compositions comprising the bifunctional compounds, and methods of treating and/or preventing diseases (e.g., proliferative diseases, cancers, benign neoplasms, pathological angiogenesis, inflammatory diseases, and autoimmune diseases). Provided also are methods of inducing the degradation of ubiquitin receptor RPN13 by administering a bifunctional compound or composition described herein, wherein one component of the bifunctional compound is a binder of an E3 ubiquitin ligase (e.g., lenalidomide, thalidomide) and another component of the compound is a binder of ubiquitin receptor RPN13 (e.g., RA190) in a subject.