Cancer treatment and research最新文献

In the previous chapters, we presented various derivations of the threshold model based on the same disease outcomes. We assumed that a decision-maker would calculate the threshold based on either mortality or morbidity outcomes. Basinga and van den Ende derived the threshold by combining both mortality and morbidity outcomes.

In this chapter, we extend the threshold model to evaluate the value of diagnostic tests or predictive models over a range of all possible thresholds by using decision curve analysis (DCA). DCA has been developed within the expected utility theory (EUT) and expected regret theory (ERT) framework.

Across the world, societies have developed different customs, traditions, and practices to memorialize the death of a loved one. Commemorations vary greatly between cultures, and may incorporate different intensities of grieving and celebration. We have selected six unique cultural observances for the deceased which have found beauty and celebration in death.

The Christian faith is founded on the principle that human life is sacred, a gift from God, the Heavenly Father. Christians live to love and glorify God. Throughout life, they witness a myriad of life events covering the spectrum from euphoric highs to devastating lows. Be it joy or sorrow, faith in God, having been established through a personal relationship with His Son, Jesus Christ of Nazareth as Savior and Lord, sustains and guides every step. The end of life is the closing earthly chapter, often shared with family members, a chaplain, parish pastor, or another spiritual care provider assisting the dying Christian with compassionate and significant conversations. It is a time to complete preparations for the final journey every Christian takes from this life into the glorious eternal life prepared in heaven with God the Heavenly Father, Jesus Christ the Savior, family, and friends who have gone before. This chapter examines various rituals and practices of the Christian faith observed during the end of life, legacy or life review, funeral practices, burial rituals following death, beliefs about the afterlife that inspire and inform the great hopes of Christian living, and bereavement support for grieving.

Seventh-day Adventists are Christians that accept the Bible as their only creed. Seventh-day Adventists are part of a movement resulting from the Protestant conviction of sola scriptura, which recognizes the Bible as the only standard of faith and practice for Christians.

Better understanding of molecular drivers and dysregulated pathways has furthered the concept of precision oncology and rational drug development. The role of DNA damage response (DDR) pathways has been extensively studied in carcinogenesis and as potential therapeutic targets to improve response to chemotherapy or overcome resistance. Treatment with small molecule inhibitors of PARP has resulted in clinical response and conferred survival benefit to patients with ovarian cancer, BRCA-mutant breast cancer, HRD-deficient prostate cancer and BRCA-mutant pancreatic cancer, leading to US Food and Drug Administration (FDA) approvals. However, the observed clinical benefit with single agent PARP inhibitors is limited to few tumor types within the relevant genetic context. Since DDR pathways are essential for repair of damage caused by cytotoxic agents, PARP inhibitors have been evaluated in combination with various chemotherapeutic agents to broaden the therapeutic application of this class of drugs. In this chapter, we discuss the combination of PARP inhibitors with different chemotherapeutics agents, clinical experience to date, lessons learnt, and future directions for this approach.

The DNA damage response (DDR) protein MTH1 is sanitising the oxidized dNTP pool and preventing incorporation of oxidative damage into DNA and has an emerging role in mitosis. It is a stress-induced protein and often found to be overexpressed in cancer. Mitotic MTH1 inhibitors arrest cells in mitosis and result in incorporation of oxidative damage into DNA and selective killing of cancer cells. Here, I discuss the leading mitotic MTH1 inhibitor TH1579 (OXC-101, karonudib), now being evaluated in clinical trials, and describe its dual effect on mitosis and incorporation of oxidative DNA damage in cancer cells. I describe why MTH1 inhibitors that solely inhibits the enzyme activity fail to kill cancer cells and discuss if MTH1 is a valid target for cancer treatment. I discuss emerging roles of MTH1 in regulating tubulin polymerisation and mitosis and the necessity of developing the basic science insights along with translational efforts. I also give a perspective on how edgetic perturbation is making target validation difficult in the DDR field.

Considerable advances in the field of cancer have been made; however, these have not been translated into similar clinical progress which results in the high prevalence and increased cancer-related mortality rate worldwide. Available treatments have several challenges such as off-target side effects, non-specific long-term potential biodisruption, drug resistance, and overall inadequate response rates and high probability of recurrence. The limitations associated with independent cancer diagnosis and therapy can be minimized by an emerging interdisciplinary research field of nanotheranostics which include successful integration of diagnosis and therapy on a single agent using nanoparticles. This may offer a powerful tool in developing innovative strategies to enable "personalized medicine" for diagnosis and treatment of cancer. Nanoparticles have been proven to be powerful imaging tools or potent agents for cancer diagnosis, treatment, and prevention. The nanotheranostic provides minimally invasive in vivo visualization of drug biodistribution and accumulation at the target site with real-time monitoring of therapeutic outcome. This chapter intends to cover several important aspects and the advances in the field of nanoparticles-mediated cancer therapeutics including nanocarrier development, drug/gene delivery, intrinsically active nanoparticles, tumor microenvironment, and nanotoxicity. The chapter represents an overview of challenges associated with cancer treatment, rational for nanotechnology in cancer therapeutics, novel concepts of multifunctional nanomaterials for cancer therapy along with their classification and their clinical prospective in different cancers. A special focus is on the nanotechnology: regulatory perspective for drug development in cancer therapeutics. Obstacles hindering further development of nanomaterials-mediated cancer therapy are also discussed. In general, the objective of this chapter is to improve our perceptive in the design and development of nanotechnology for cancer therapeutics.

Malnutrition in cancer patients is highly prevalent. The metabolic and physiologic changes associated with the disease and the side effects of treatment regimens all combine together to produce a detrimental effect on the patient's nutritional status. A poor nutritional status significantly reduces the efficacy of treatment methods and the patient's overall chances of survival. Therefore, an individualized nutrition care plan is essential to counter malnutrition in cancer. Nutritional assessment is the first step of this process which sets the foundation for developing an effective intervention plan. Currently, there is no single standard method for nutritional assessment in cancer. Hence, to get a true picture of the patient's nutritional state, a comprehensive analysis of all aspects of the patient's nutritional status is the only reliable strategy. The assessment includes anthropometric measurements and evaluation of body protein status, body fat, inflammation markers, and immune markers. A thorough clinical examination which factors in the medical history and physical signs, along with the dietary intake patterns of the patient, is also important components of nutritional assessment of cancer patients. To facilitate with the process, various nutritional screening tools like patient-generated subjective global assessment (PGSGA), nutrition risk screening (NRS), and malnutrition screening tool (MST) have been developed. While these tools have their own benefits, they only give a glimpse of the nutritional problems and do not bypass the need for a complete assessment employing various methods. This chapter covers all four of the elements of nutritional assessment for cancer patients in detail.

Oncolytic virotherapy opens up avenues for cancer treatment by selectively targeting the cancer cells and destructs them either through direct lysis or by inducing an immune response in the tumor microenvironment. This platform technology utilizes a diverse range naturally existing or genetically modified oncolytic viruses for their immunotherapeutic potential. Due to the limitations associated with the conventional cancer therapies, immunotherapies using oncolytic viruses (OVs) have generated a great deal of interest in the modern era. Currently, several oncolytic viruses have entered clinical trials and have proven successful for a number of different cancers as monotherapies as well as in combination with the standard treatment methods like chemotherapy, radiotherapy, or immunotherapy. Efficacy of OVs can be further enhanced by utilizing several approaches. Efforts of the scientific community for getting better knowledge of individual patient tumor immune responses will enable medical community to treat cancer patients more precisely. In this regard, OV seems to be a part of multimodality cancer treatment option in the near future. In this chapter, the fundamental characteristics and mechanism of actions of oncolytic viruses are initially described and then overview of the important clinical trials of various oncolytic viruses for a number of cancers is presented.