scholarly journals Uncertain diagnosis and prognosis in advanced melanoma: a qualitative study of the experiences of bereaved carers in a time of immune and targeted therapies

2019 ◽  
Vol 180 (6) ◽  
pp. 1368-1376 ◽  
Author(s):  
J.A. Fox ◽  
D. Langbecker ◽  
J. Rosenberg ◽  
S. Ekberg
Keyword(s):  
Qualitative Study ◽  
Targeted Therapies ◽  
Advanced Melanoma ◽  
Diagnosis And Prognosis

scholarly journals Oxidative Stress-Related Mechanisms in Melanoma and in the Acquired Resistance to Targeted Therapies

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1942
Author(s):  
Stefania Pizzimenti ◽  
Simone Ribero ◽  
Marie Angele Cucci ◽  
Margherita Grattarola ◽  
Chiara Monge ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Targeted Therapies ◽  
Current Knowledge ◽  
Mapk Pathway ◽  
Acquired Resistance ◽  
Genetic Alterations ◽  
Advanced Melanoma ◽  
Braf Mutations ◽  
Downstream Signaling ◽  
Activating Mutations

Melanoma is a highly aggressive cancer with the poorest prognosis, representing the deadliest form of skin cancer. Activating mutations in BRAF are the most frequent genetic alterations, present in approximately 50% of all melanoma cases. The use of specific inhibitors towards mutant BRAF variants and MEK, a downstream signaling target of BRAF in the MAPK pathway, has significantly improved progression-free and overall survival in advanced melanoma patients carrying BRAF mutations. Nevertheless, despite these improvements, resistance still develops within the first year of therapy in around 50% of patients, which is a significant problem in managing BRAF-mutated advanced melanoma. Understanding these mechanisms is one of the mainstreams of the research on BRAFi/MEKi acquired resistance. Both genetic and epigenetic mechanisms have been described. Moreover, in recent years, oxidative stress has emerged as another major force involved in all the phases of melanoma development, from initiation to progression until the onsets of the metastatic phenotype and chemoresistance, and has thus become a target for therapy. In the present review, we discuss the current knowledge on oxidative stress and its signaling in melanoma, as well as the oxidative stress-related mechanisms in the acquired resistance to targeted therapies.

scholarly journals Palliative care in the context of immune and targeted therapies: A qualitative study of bereaved carers’ experiences in metastatic melanoma

2020 ◽  
Vol 34 (10) ◽  
pp. 1351-1360 ◽  
Author(s):  
Jennifer A Fox ◽  
John Rosenberg ◽  
Stuart Ekberg ◽  
Danette Langbecker
Keyword(s):  
Palliative Care ◽  
Targeted Therapy ◽  
Qualitative Study ◽  
Metastatic Melanoma ◽  
End Of Life ◽  
Targeted Therapies ◽  
Treatment Options ◽  
Family Needs ◽  
Term Survival ◽  
Treatment Paradigm

Background: Immune and targeted therapies continue to transform treatment outcomes for those with metastatic melanoma. However, the role of palliative care within this treatment paradigm is not well understood. Aim: To explore bereaved carers’ experiences of immune and targeted therapy treatment options towards end of life for patients with metastatic melanoma. Design: An interpretive, qualitative study using a social constructivist framework was utilised. Interviews were recorded, transcribed and analysed using grounded theory methods. Setting/participants: Participants ( n = 20) were bereaved carers of patients who had received some form of immune and/or targeted therapy at one of three Australian metropolitan melanoma treatment centres. Results: Carers struggled to reconcile the positive discourse around the success of immune and targeted therapies in achieving long-term disease control, and the underlying uncertainty in predicting individual responses to therapy. Expectations that immune and targeted therapies necessarily provide longer-term survival were evident. Difficulty in prognostication due to clinical uncertainty and a desire to maintain hope resulted in lack of preparedness for treatment failure and end of life. Conclusion: Immune and targeted therapies have resulted in increased prognostic challenges. There is a need to engage, educate and support patients and carers to prepare and plan amid these challenges. Educational initiatives must focus on improving communication between patients, carers and clinicians; the differences between palliative and end-of-life care; and increased competency of clinicians in having goals-of-care discussions. Clinicians must recognise and communicate the benefit of collaborative palliative care to meet patient and family needs holistically and comprehensively.

Emerging Strategies in Systemic Therapy for the Treatment of Melanoma

2018 ◽  
pp. 751-758 ◽  
Author(s):  
Paolo A. Ascierto ◽  
Keith Flaherty ◽  
Stephanie Goff
Keyword(s):  
Targeted Therapy ◽  
Targeted Therapies ◽  
De Novo ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Acquired Resistance ◽  
Interleukin 2 ◽  
Advanced Melanoma ◽  
Adoptive Cell Transfer ◽  
Mek Inhibition

Recent years have seen major improvements in survival of patients with advanced melanoma with the advent of various novel systemic immunotherapies and targeted therapies. As our understanding of these agents and their various mechanisms of action improves, even more impressive outcomes are being achieved through use of various combination strategies, including the combining of different immunotherapies with one another as well as with other modalities. However, despite the improved outcomes that have been achieved in advanced melanoma, responses to treatment are heterogeneous and may not always be durable. Additional advances in therapy are required, and several emerging strategies are a focus of interest. These include the investigation of several new immunotherapy and/or targeted therapy combinations, such as checkpoint inhibitors (anti–PD-1/anti–CTLA-4) with other immunotherapies (e.g., indoleamine 2,3 dioxygenase [IDO] inhibitors, antilymphocyte activation 3 [anti–LAG-3], histone deacetylase [HDAC] inhibitors, Toll-like receptor 9 [TLR-9] agonists, antiglucocorticoid-induced tumor necrosis factor receptor [anti-GITR], pegylated interleukin-2 [IL-2]), combined targeted therapies (e.g., MEK and CDK4/6 coinhibition), and combined immunotherapy and targeted therapy (e.g., the triplet combination of BRAF/MEK inhibition with anti–PD-1s). The identification of novel therapeutic targets in the MAP kinase pathway also offers opportunities to improve outcomes by overcoming de novo and acquired resistance to BRAF/MEK inhibition (e.g., the development of ERK inhibitors). In addition, adoptive cell transfer, the infusion of large numbers of activated autologous lymphocytes, may have a potential role in patients whose disease has progressed after immunotherapy. Taken together, these new approaches offer further potential to increase systemic treatment options and improve long-term outcomes for patients with advanced melanoma.

scholarly journals Qualitative study of bereaved carers’ experiences in advanced melanoma

2019 ◽  
Vol 180 (6) ◽  
Author(s):  
J.A. Fox ◽  
D. Langbecker ◽  
J. Rosenberg ◽  
S. Ekberg
Keyword(s):  
Qualitative Study ◽  
Advanced Melanoma

scholarly journals Hearing the voices of children diagnosed with a life-threatening or life-limiting illness and their parents’ accounts in a palliative care setting: A qualitative study

2021 ◽  
pp. 026921632110002
Author(s):  
Estera Ciobanu ◽  
Nancy Preston
Keyword(s):  
Palliative Care ◽  
Qualitative Study ◽  
Care Service ◽  
Death And Dying ◽  
Palliative Care Service ◽  
Diagnosis And Prognosis ◽  
Parents And Children ◽  
Palliative Care Setting ◽  
Life Threatening ◽  
Limiting Condition

Background: Exploring children’s experiences of a life-threatening or life-limiting diagnosis is essential in offering appropriate care for them. There have been few studies examining these and they are often from the parent’s perspective. Even if adults are frequently unwilling to share information with children, they become aware of their diagnosis and prognosis. The theory of awareness contexts provided a theoretical framework through which it can be understood what children knew about their condition. Aim: To advance the understanding of the experiences of children with a life-threatening or life-limiting condition. Design: A qualitative study using dyadic interviews and thematic analysis. Setting/participants: Ten children between 14 to 17 years old with a life-threatening or life-limiting illness who were supported by a palliative care service in Romania. Interviews were also undertaken with their mothers. Results: Interview data demonstrated that there was a gap in the child’s experience and understanding of their condition compared to their parents. The data produced six major themes: awareness of the illness, death and dying, the spiritual response to illness, the emotional response to illness, striving for normality and independence and coping strategies. The study showed that children can read subtle cues or they may talk with other children to learn about their illness when information is not openly available to them. Conclusions: Children in the study often know more about their condition than their parents realised. Using this understanding, healthcare professionals can advise parents and children about how to communicate with one another which would enable the children to give voice to their thoughts, emotions and experiences.

scholarly journals BRAF inhibitor resistance of melanoma cells triggers increased susceptibility to natural killer cell-mediated lysis

2020 ◽  
Vol 8 (2) ◽  
pp. e000275
Author(s):  
Alexandra Frazao ◽  
Louise Rethacker ◽  
Géraldine Jeudy ◽  
Marina Colombo ◽  
Eric Pasmant ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Nk Cells ◽  
Natural Killer ◽  
Cell Lines ◽  
Targeted Therapies ◽  
Nk Cell ◽  
Advanced Melanoma ◽  
Mek Inhibition ◽  
Melanoma Patients ◽  
Induced Apoptosis

BackgroundTargeted therapies and immunotherapies are first-line treatments for patients with advanced melanoma. Serine–threonine protein kinase B-RAF (BRAF) and mitogen-activated protein kinase (MEK) inhibition leads to a 70% response rate in patients with advanced melanoma with a BRAFV600E/K mutation. However, acquired resistance occurs in the majority of patients, leading to relapse. Immunotherapies that activate immune cytotoxic effectors induce long-lasting responses in 30% of patients. In that context, combination of targeted therapies with immunotherapy (IT) is a promising approach. We considered boosting natural killer (NK) cell tumor immunosurveillance, as melanoma cells express stress-induced molecules and activate NK cell lysis.MethodsHere we have generated vemurafenib (a BRAF inihibitor)-resistant (R) cells from BRAFV600E SK28 and M14-sensitive (S) melanoma cell lines and investigated how resistance interferes with immunogenicity to NK cells. We determined the levels of several soluble molecules including NK ligands in 61 melanoma patients at baseline and 6 months M post-treatment with targeted therapies or immunotherapies.ResultsVemurafenib resistance involved activation of p-AKT in SK28R and of p-MEK/p-ERK in M14R cells and was accompanied by modulation of NK ligands. Compared with S cells, SK28R displayed an increased expression of natural killer group 2 D (NKG2D) receptor ligands (major histocompatibility complex class (MHC) I chain-related protein A (MICA) and UL16-binding protein 2 (ULBP2)) whereas M14R exhibited decreased ULBP2 . SK28R and M14R cells induced higher NK degranulation and interferon gamma secretion and were more efficiently lysed by donor and patient NK cells. SK28R showed increased tumor necrosis factor-related apoptosis-inducing ligand receptor II (TRAIL-RII) expression and TRAIL-induced apoptosis, and TRAIL-induced apoptosis of M14R was decreased. Combined BRAF/MEK inhibitors abrogated the growth of SK28S, M14S, and M14R cells, while growth of SK28R was maintained. BRAF/MEK inhibition attenuated NK activity but R cell lines activated polyfunctional NK cells and were lysed with high efficiency. We investigated the relationship of soluble NK ligands and response to treatment in a series of melanoma patients. Soluble NKG2D ligands known to regulate the receptor function have been associated to cancer progression. Serum analysis of patients treated with target therapies or IT indicates that soluble forms of NK ligands (MICA, B7H6, programmed cell death ligand 1, and carcinoembryonic antigen cell adhesion molecule 1) may correlate with clinical response.ConclusionThese results support strategies combining targeted therapies and NK-based immunotherapies.

scholarly journals Patient voice on management of facial dermatological adverse events with targeted therapies: a qualitative study

2019 ◽  
Vol 3 (1) ◽  
Author(s):  
Kaori Yagasaki ◽  
Hayato Takahashi ◽  
Takeshi Ouchi ◽  
Jun Yamagami ◽  
Yasuo Hamamoto ◽  
...  
Keyword(s):  
Qualitative Study ◽  
Adverse Events ◽  
Targeted Therapies ◽  
Patient Voice

When cancer cannot be cured: A qualitative study on relationship changes in couples facing advanced melanoma

2016 ◽  
Vol 14 (6) ◽  
pp. 652-663
Author(s):  
Natalie Drabe ◽  
Josef Jenewein ◽  
Steffi Weidt ◽  
Lucia Engeli ◽  
Caroline Meier ◽  
...  
Keyword(s):  
Content Analysis ◽  
Qualitative Study ◽  
Qualitative Content Analysis ◽  
Advanced Melanoma ◽  
Communication Patterns ◽  
Spare Time ◽  
Complex Picture ◽  
Distance Regulation ◽  
Changes Over Time ◽  
Over Time

AbstractObjective:The aim of this qualitative study was to gain a deeper understanding about couples' relationship changes over time (the first six months) after one partner is diagnosed with an incurable advanced melanoma (stage III or IV).Method:In semistructured interviews, eight patients and their partners were asked separately about potential changes in their relationship since diagnosis. The same questions were asked again six months later, but focusing on relationship changes over the preceding six months. Some 32 audiotaped interviews were analyzed applying qualitative content analysis.Results:At baseline (t1), relationship changes were mostly reported in terms of caring, closeness/distance regulation, and communication patterns. While changes in caregiving and distance/closeness regulation remained main issues at six months follow-up (t2), greater appreciation of the relationship and limitations in terms of planning spare time also emerged as major issues. Unexpectedly, 50% of patients and partners reported actively hiding their negative emotions and sorrows from their counterparts to spare them worry. Furthermore, qualitative content analysis revealed relationship changes even in those patients and partners who primarily reported no changes over the course of the disease.Significance of results:Our findings revealed a differentiated and complex picture about relationship changes over time, which also might aid in the development of support programs for couples dealing with advanced cancer, focusing on the aspects of caring, closeness/distance regulation, and communication patterns.

Sign in / Sign up

Export Citation Format

Share Document