Cancer Journal

The gut microbiome and liver are anatomically and functionally connected. The impact of the gut microbiota or microbial metabolites on liver cancer progression via immune cells has been recently revealed across various preclinical models. Commensal gut microbes of liver cancer patients differ from control subjects, and their composition is affected by the etiology of the hepatocellular carcinoma. The gut microbiota represents a potential novel target for intervention as shown in patients with melanoma, but we still lack data in patients with hepatocellular carcinoma...

Changes in the gut microbiome have been increasingly shown to accompany oncogenesis across various tumors. Similarly, microbial dysbiosis was found to be associated with pancreatic cancer progression and survival outcomes, expanding the field of tumor microenvironment research in pancreatic cancer. Mechanistic studies in pancreatic cancer models implicate components of the gut and pancreatic cancer microbiome in regulating tumorigenesis by altering cancer cell signaling, modulating immune function, and influencing the efficacy of current therapies in pancreatic cancer...

No abstract text is available yet for this article.

Cancer is defined by the presence of uncontrollable cell growth, whereby improper proliferative signaling has overcome regulation by cellular mechanisms. Transcription factors are uniquely situated at the helm of signaling, merging extracellular stimuli with intracellular responses. Therefore, this class of proteins plays a pivotal role in coordinating the correct gene expression levels for maintaining normal cellular functions. Dysregulation of transcription factor activity unsurprisingly drives tumorigenesis and oncogenic transformation...

Vaccine strategies for cancer differ from infectious disease in focusing mainly on clearing rather than preventing disease. Here we survey general vaccine strategies and combination therapy concepts being investigated for cancer treatment, with a focus on tumor antigens rather than cancer-inducing viruses or microorganisms. Many tumor antigens are "altered-self" and tend to arouse weaker immune responses than "foreign" antigens expressed by infectious agents. Further, unlike an infectious disease patient, a cancer patient's immune system is damaged, suppressed, or senescent and mainly tolerant of their disease...

Genetically engineered chimeric antigen receptor (CAR) T-cell therapy leverages the ability of the immune system to eliminate tumors and redirects cytotoxic functions toward cells expressing specified tumor-restricted antigens. Although 6 CAR T-cell therapies have received Food and Drug Administration (FDA) approval for the treatment of many hematological malignancies, limitations involving T cell-intrinsic, T cell-extrinsic, and therapeutic factors remain in the treatment of both liquid and solid tumors. Chimeric antigen receptor design, signals from the tumor microenvironment, tumor antigen escape mechanisms, and systemic inflammatory consequences of CAR T-cell infusion all influence the efficacy and feasibility of CAR T-cell therapy in different malignancies...

Cellular immunotherapy of cancer in the form of chimeric antigen receptor-modified T-cell therapy has become a standard treatment for lymphoid and more recently plasma cell malignancies. Although their successes in these cancers represent a breakthrough for adoptive cell therapy, there are several challenges to their continued growth in the field of cancer medicine. In this review, we discuss the progress made thus far toward achieving "off-the-shelf" accessibility of cell therapies that has the potential to greatly offset the costs associated with the current practice of making patient-specific products...

Cancer treatment has dramatically changed over the last decade with the development of immunotherapy. Therapies including immune cytokines, immune checkpoint inhibition, intratumoral therapies, and cellular therapies are already widely used in the oncology clinic. Active development continues in these areas and in the development of vaccines, bispecific therapies, and more refined cellular therapies. In this review, we will examine the role that immune therapy has in cancer treatment and explore areas of future development...

The vast amount of gene expression profiling data of bulk tumors and cell lines available in the public domain represents a tremendous resource. For any major cancer type, expression data can identify molecular subtypes, predict patient outcome, identify markers of therapeutic response, determine the functional consequences of somatic mutation, and elucidate the biology of metastatic and advanced cancers. This review provides a broad overview of gene expression profiling in cancer (which may include transcriptome and proteome levels) and the types of findings made using these data...

Precision cancer care, for essentially all cancer types, now requires molecular diagnostics to assess mutations, chromosomal alterations, and gene expression to personalize treatments for individual patients. Advances in the diagnostics and treatment options have moved the field forward from fundamental discoveries beginning in the 1960s to the development of many targeted therapies that can be as specific as targeting a single-base-pair mutation. Herein is a brief historical perspective on cancer precision medicine with current diagnostic, prognostic, and treatment stratification guidance for early- and late-stage cancers...

No abstract text is available yet for this article.

Antibody-drug conjugates (ADCs) have been revolutionary in improving personalized therapy of cancer. Through combining monoclonal antibodies, which are targeted to tumor-specific antigens, and cytotoxic agents, ADCs lead to selective delivery of active components, also called payloads, to cancerous cells while sparing healthy body cells from possible collateral damage. Adverse events, however, can still develop because of early release of the payload or cross-expression of targets by normal cells leading to collateral damage...

Antibody-drug conjugates (ADCs) have emerged as a treatment option for patients with relapsed/refractory multiple myeloma with the regulatory approval of the first-in-class B-cell maturation antigen (BCMA) ADC belantamab mafodotin. Other BCMA and non-BCMA ADCs are currently in clinical development. Whereas ADCs allow antigen-specific delivery of a chemomoiety to myeloma cells, on-target and off-target effects related to antigen target, antibody, linker, and chemomoiety can also limit these approaches. We review the clinical development of belantamab mafodotin and ongoing efforts to enhance its efficacy while mitigating ocular toxicity...

Despite the curative potential of autologous transplantation and chimeric antigen receptor T cells in lymphoma, many patients are ineligible, or their disease progresses after these treatments. In this context, antibody drug conjugates (ADCs) have demonstrated very promising efficacy in lymphomas. Antibody drug conjugates are monoclonal antibodies covalently linked to a cytotoxic drug. Because of its highly specific targeting abilities and powerful killing effects, it has become a promising technology for developing anticancer drugs in recent years...

Antibody-drug conjugates are becoming increasingly important in the treatment of many cancer types. The 3 main structural components-antibody, linker, and payload-each contribute to the toxicity profiles of these drugs. In addition to cytopenias and gastrointestinal adverse effects attributed to the chemotherapy payloads, each drug has specific toxicities that are not commonly described in oncology. Ocular, pulmonary, dermatologic, and neurologic toxicities are particularly nuanced. This review provides a framework for clinicians to analyze current and future antibody-drug conjugates and a description of the unique monitoring, preventive, and supportive care measures for these agents...

Antibody-drug conjugates (ADCs) deliver effective medications to tumor cells that express specific antigens, maximizing efficacy and reducing adverse effects. Because ado-trastuzumab emtansine was approved in 2013, 5 ADCs received US Food and Drug Administration approval for solid tumor treatment. Technical advancements in the development of each component of ADCs allowed novel monoclonal antibodies, linkers, and payloads to increase drug transport to malignant cells and drug activity even in cancers with heterogeneous antigen expression...

Targeted therapy in oncology brings with it the promise to maximize cancer cell cytotoxicity with minimal off-target effects. Antibody-drug conjugates (ADCs), an important group of such targeted agents, consist of a monoclonal antibody conjugated to a potent cytotoxic drug. In the field of leukemia, ADCs form an important component of therapeutic arsenal through the use of gemtuzumab ozogamicin in acute myeloid leukemia and inotuzumab ozogamicin (InO) in B-cell acute lymphoblastic leukemia, 2 approved agents...

Antibody-drug conjugates (ADCs) are designed to deliver cytotoxic payloads to distinctive target-expressing cancer cells. Following internalization, the ADCs are routed to different compartments in the cells, where cleavage of the linker causes release of the cytotoxic cargo. With such a delivery system, more effective payloads can reach cancer cells, allowing for more efficient treatment and dosing schedule. The monoclonal antibody (mAb) component of ADC plays a crucial role in the effective targeting of cancer cell-specific antigens while minimizing binding to normal cells...

The therapeutic landscape of patients with breast cancer has changed significantly with the introduction of antibody-drug conjugates (ADCs). Although human epidermal growth factor receptor 2 (HER2) has been the centerpiece of ADC development, potentially any surface antigen with differential expression between tumor and normal cells may be suitable for targeting with ADCs. Exploration of new targets is critical to expand the fraction of patients who can benefit from ADCs. Sacituzumab govitecan, an anti-trophoblast cell surface antigen 2 ADC, is the only non-anti-HER2 ADC approved for breast cancer to date, with several novel ADCs directed against novel targets (e...

An antibody-drug conjugate (ADC) comprises a monoclonal antibody that is specific to a tumor cell protein, bound to a cytotoxic agent, known as the payload. The use of ADCs is already common practice in several cancers, thanks to their efficacy and potentially more manageable toxicity profile, resulting from the release of the cytostatic payload directly in the tumors. Currently, early-phase trials of ADCs in non-small cell lung cancer are rapidly gaining ground, with promising results targeting HER2 (human epidermal growth factor 2), HER3, TROP2 (trophoblast cell surface antigen 2), MET, CEACAM5 (carcinoembryonic antigen-related cell adhesion molecule 5), and PTK7 (tyrosine protein kinase-like 7)...