Cancer treatment and research最新文献

A subset of patients with pancreatic adenocarcinomas (PDAC) harbor mutations that are exploitable in the context of DNA-damage response and repair (DDR) inhibitory strategies. Between 8-18% of PDACs harbor specific mutations in the DDR pathway such as BRCA1/2 mutations, and a higher prevalence exists in high-risk populations (e.g., Ashkenazi Jews). Herein, we will review the current trials and data on the treatment of PDAC patients who harbor such mutations and who appear sensitive to platinum and/or poly ADP ribose polymerase inhibitor (PARPi) based therapies due to a concept known as synthetic lethality. Although this current best-in-class precision treatment shows clinical promise, the specter of resistance limits the extent of therapeutic responses. We therefore also evaluate promising pre-clinical and clinical approaches in the pipeline that may either work with existing therapies to break resistance or work separately with combination therapies against this subset of PDACs.

Poly (ADP-ribose) polymerase (PARP) inhibitors have significantly improved treatment outcomes of homologous recombination (HR) repair-deficient cancers. While the activity of these agents is largely linked to multiple mechanisms underlying the synthetic lethality of PARP inhibition and HR deficiency, emerging data suggest that their efficacy is also tied to their effects on the immune microenvironment and dependent upon cytotoxic T-cell activation. Effects observed in preclinical models are currently being validated in on-treatment biopsy samples procured from patients enrolled in clinical trials. Although this work has stimulated the development of combinations of PARP inhibitors with immunomodulatory agents, results to date have not demonstrated the superiority of combined PARP inhibition and immune checkpoint blockade compared with PARP inhibition alone. These results have stimulated a more comprehensive assessment of the immunosuppressive components of the tumor microenvironment that must be addressed so that the efficacy of PARP inhibitor agents can be maximized.

The delivery of culturally congruent, person-centered, family-focused quality care requires an exploration of the values, beliefs, and preferences of those we serve [13]. Nuanced advance care planning conversations lay the foundation for shared decision making and promotes the delivery of goal-concordant care. This chapter will provide clinicians with guidance and resources to aid this process with a focus on contextualized communication with those with serious illness.

Members of The Church of Jesus Christ of Latter-day Saints accept modern medical science and believe in receiving medical treatment along with seeking divine guidance and inspiration. At the same time, situations of life and death can throw people into stressful places they have never been before, bringing challenges even to people of deep faith. Medical professionals can better support Latter-day Saints if they understand how their beliefs answer questions about life and death, including, "Where did I come from? Why am I here on earth? Where am I going after death?" This chapter examines the origin, beliefs, and practices of the Church to give medical professionals a foundational understanding of what is important to members at the end of life. It includes sections on beliefs and practices, including those relevant to medical treatment, end-of-life decisions, death and burial.

This chapter examines the need and importance of cultural competency in providing End of Life care. The United States is diverse in culture. As we evolve into a multiethnic society, our healthcare providers must be able to manage this shift in establishing and providing care that is culturally appropriate and effective. Americans have the rights to provide autonomy and independent decision-making related to their healthcare; however, these core values may not align with ethnic and culturally diverse groups in the United States. Conflicts often lead to health disparities and resulting in care that is fragmented and inadequate. The difference in values result in improper management and miscommunication with patients and families that significantly affect care, especially during end-of-life.

Doula is a Greek word meaning "woman caregiver", and an "experienced woman who helps other women" [4].

RNA modifications have recently been recognized as essential posttranscriptional regulators of gene expression in eukaryotes. Investigations over the past decade have revealed that RNA chemical modifications have profound effects on tumor initiation, progression, refractory, and recurrence. Tumor cells are notorious for their robust plasticity in response to the stressful microenvironment and undergo metabolic adaptations to sustain rapid cell proliferation, which is termed as metabolic reprogramming. Meanwhile, cancer-associated metabolic reprogramming leads to substantial alterations of intracellular and extracellular metabolites, which further reshapes the tumor microenvironment (TME). Moreover, cancer cells compete with tumor-infiltrating immune cells for the limited nutrients to maintain their proliferation and function in the TME. In this chapter, we review recent interesting findings on the engagement of epitranscriptomic pathways, especially the ones associated with N⁶-methyladenosine (m⁶A), in the regulation of cancer metabolism and the surrounding microenvironment. We also discuss the promising therapeutic approaches targeting RNA modifications for anti-tumor therapy.

Cancer remains one of the serious health hazards and major causes of human mortality across the world. Despite the development of many typical antineoplastic drugs and introduction of novel targeted agents, chemoresistance constitutes a major challenge in the effective therapeutic management of cancer. Drug inactivation, efflux of anticancer agents, modification of target sites, enhanced repair of DNA damage, apoptosis failure and induction of epithelial-mesenchymal transition are the principal mechanisms of cancer chemoresistance. Moreover, epigenetics, cell signaling, tumor heterogeneity, stem cells, microRNAs, endoplasmic reticulum, tumor microenvironment and exosomes have also been implicated in the multifaceted phenomenon of anticancer drug resistance. The tendency of resistance is either intrinsically possessed or subsequently acquired by cancerous cells. From clinical oncology standpoint, therapeutic failure and tumor progression are the most probable consequences of cancer chemoresistance. Combination therapy can help to overcome the issue of drug resistance, and therefore, the development of such treatment regimens is recommended for counteracting the emergence and dissemination of cancer chemoresistance. This chapter outlines the current knowledge on underlying mechanisms, contributory biological factors and likely consequences of cancer chemoresistance. Besides, prognostic biomarkers, diagnostic methods and potential approaches to overcome the emergence of antineoplastic drug resistance have also been described.

In past quarter of the century, much has been understood about the genetic variation and abnormal genes that activate cancer in humans. All the cancers somehow possess alterations in the DNA sequence of cancer cell's genome. In present, we are heading toward the era where it is possible to obtain complete genome of the cancer cells for their better diagnosis, categorization and to explore treatment options.

Clinical management is rarely based on the collection of one data item. Instead, it is typically characterized by the continuous collection and evaluation of clinical data (symptoms, signs, laboratory, imaging tests, etc.) to establish a platform for further management decisions.