A Case Report on Breast Cancer Following Mantle Radiation for Hodgkin Lymphoma: Screening and Management.

Hodgkin lymphoma survivors who received mantle radiation are at risk of developing secondary malignant neoplasms. There is no established recommended screening guideline for this population. We discuss the case of a patient with a history of Hodgkin lymphoma status post-mantle field radiation, thyroid cancer status post-thyroidectomy, and now breast cancer following mantle radiation.

Immune checkpoint inhibitors of PD-L1 as cancer therapeutics.

Since the discovery of immune checkpoint proteins, there has been a special interest in developing antibodies that block programmed cell death 1 receptor (PD-1) and programmed cell death receptor ligand 1 (PD-L1) for a subset of cancer patients. PD-1 signaling negatively regulates T cell-mediated immune responses and serves as a mechanism for tumors to evade an antigen-specific T cell immunologic response. It plays a role in promoting cancer development and progression by enhancing tumor cell survival.

Novel agents for advanced pancreatic cancer.

Pancreatic cancer is relatively insensitive to conventional chemotherapy. Therefore, novel agents targeting dysregulated pathways (MAPK/ERK, EGFR, TGF-β, HEDGEHOG, NOTCH, IGF, PARP, PI3K/AKT, RAS, and Src) are being explored in clinical trials as monotherapy or in combination with cytotoxic chemotherapy. This review summarizes the most recent advances with the targeted therapies in the treatment of patients with advanced pancreatic cancer.

Novel ALK inhibitors in clinical use and development.

Anaplastic lymphoma kinase 1 (ALK-1) is a member of the insulin receptor tyrosine kinase family. ALK-1 was initially found in anaplastic large cell lymphoma (ALCL). ALK mutations have also been implicated in the pathogenesis of non-small cell lung cancer (NSCLC) and other solid tumors.

Management of mantle cell leukemia with cardiac involvement leading to cardiogenic shock.

Mantle cell lymphoma is an aggressive subtype of B cell non-Hodgkin lymphoma. It can progress to leukemic phase but frank leukemic picture at initial presentation is not common. Leukemic phase indicates advance stage of the disease and generally associated with extensive extra-nodal involvement.

Ibrutinib and indolent B-cell lymphomas.

Most patients with indolent B-cell lymphomas fail to achieve complete remission with current treatment approaches and invariably relapse. During the past decade, innovative immunochemotherapy strategies have substantially improved disease control rates but not survival, thus providing the rationale for development of novel agents targeting dysregulated pathways that are operable in these hematological malignancies. Ibrutinib, a novel first-in-human Bruton's tyrosine kinase (BTK) inhibitor, has progressed into phase III trials after early-phase clinical studies demonstrated effective target inhibition, increased tumor response rates, and significant improvement in survival, particularly in patients with indolent B-cell lymphomas.

STAT inhibitors for cancer therapy.

Signal Transducer and Activator of Transcription (STAT) proteins are a family of cytoplasmic transcription factors consisting of 7 members, STAT1 to STAT6, including STAT5a and STAT5b. STAT proteins are thought to be ideal targets for anti-cancer therapy since cancer cells are more dependent on the STAT activity than their normal counterparts. Inhibitors targeting STAT3 and STAT5 have been developed.

Phosphatidylinositol 3-kinase (PI3K) inhibitors as cancer therapeutics.

Phosphatidylinositol 3-kinases (PI3Ks) are lipid kinases that regulate diverse cellular processes including proliferation, adhesion, survival, and motility. Dysregulated PI3K pathway signaling occurs in one-third of human tumors. Aberrantly activated PI3K signaling also confers sensitivity and resistance to conventional therapies.

Ibrutinib and novel BTK inhibitors in clinical development.

Small molecule inhibitors targeting dysregulated pathways (RAS/RAF/MEK, PI3K/AKT/mTOR, JAK/STAT) have significantly improved clinical outcomes in cancer patients. Recently Bruton's tyrosine kinase (BTK), a crucial terminal kinase enzyme in the B-cell antigen receptor (BCR) signaling pathway, has emerged as an attractive target for therapeutic intervention in human malignancies and autoimmune disorders. Ibrutinib, a novel first-in-human BTK-inhibitor, has demonstrated clinical effectiveness and tolerability in early clinical trials and has progressed into phase III trials.

Novel agents for chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is a heterogeneous group of B-cell neoplasm. CLL is typically sensitive to a variety of cytotoxic agents, but relapse frequently occurs with conventional approaches. The treatment of CLL is evolving rapidly with the introduction of novel drugs, such as bendamustine, ofatumumab, lenalidomide, ibrutinib, idelalisib, veltuzumab, XmAb5574, navitoclax, dasatinib, alvespimycin, and TRU-016.

MEK and the inhibitors: from bench to bedside.

Four distinct MAP kinase signaling pathways involving 7 MEK enzymes have been identified. MEK1 and MEK2 are the prototype members of MEK family proteins. Several MEK inhibitors are in clinical trials.