Here, we show that microRNA-200a decreases CDK6 expression and thus reduces the response of CDK4/6 inhibitor in highly proliferative metastatic melanoma.
By somatically inactivating Lkb1 with K-Ras activation (±p53 loss) in murine melanocytes, we observed variably pigmented and highly metastatic melanoma with 100% penetrance.
In conclusion, our study suggests, for the first time, that while cPKCs don't embody a pertinent therapeutic target, inhibition of PKD1 represents a novel attractive approach for the treatment of metastatic melanoma.
Selumetinib plus dacarbazine versus placebo plus dacarbazine as first-line treatment for BRAF-mutant metastatic melanoma: a phase 2 double-blind randomised study.
The recent regulatory approval of RAF inhibitors and a MAP-ERK kinase (MEK) inhibitor for metastatic melanoma provides clinical validation of tumor dependency on this pathway.
Recent successes in the development of new therapies for metastatic melanoma, such as mitogen-activated protein kinase pathway inhibitors, anticytotoxic T lymphocyte-associated antigen-4, and programmed cell death protein 1/programmed cell death ligand 1 (PD-L1) pathway-blocking antibodies, as well as combination strategies, all yielded promising results, changing the continually evolving landscape of therapeutic options for patients with melanoma.
The combination of anti-VEGF blockade (bevacizumab) with immune checkpoint anti-CTLA-4 blockade (ipilimumab) in a phase I study showed tumor endothelial activation and immune cell infiltration that were associated with favorable clinical outcomes in patients with metastatic melanoma.
The NRAS (Q61R) IHC assay is reliable and specific for the evaluation of the Q61R mutation status in metastatic melanoma and may be an alternative to molecular biology in evaluation of metastatic melanoma in routine practice.
Preliminary observations on soluble programmed cell death protein-1 as a prognostic and predictive biomarker in patients with metastatic melanoma treated with patient-specific autologous vaccines.
However, recent breakthroughs have brought new hopes for patients and providers.While targeted therapy with BRAF and MEK inhibitors represents an important cornerstone in the treatment of metastatic melanoma, this chapter carefully reviews the past and current therapy options available, with a significant focus on immunotherapy-based approaches.
Compared with vemurafenib, dabrafenib is a more recent BRAF inhibitor approved by the Food and Drug Administration in May 2013 for metastatic melanoma; fewer data are available in the current literature regarding cutaneous toxicity.
Furthermore, we have found an association between the presence of N-ras mutations and clinical response to immunotherapy with interleukin-2 plus interferon in a group of stage IV melanoma patients.
Although cAMP elevation did not alter the sensitivity of metastatic melanoma cells to BRAF(V600E) and MEK inhibitors, the EPAC-RAP1 axis appears to contribute to resistance to MAPK pathway inhibition.
This phase Ib study (ClinicalTrials.gov, number NCT01656642 ) evaluated the safety and anti-tumor activity of combining atezolizumab (anti-PD-L1) with vemurafenib (BRAF inhibitor), or cobimetinib (MEK inhibitor) + vemurafenib, in patients with BRAF<sup>V600</sup>-mutated metastatic melanoma.
In 1998, high-dose interleukin-2 (IL-2) was the first immunotherapy approved for the treatment of metastatic melanoma based on durable objective responses documented in a subset of patients but widespread utilization was limited by significant toxicity.
We report a patient with BRAF mutant metastatic melanoma treated with the BRAFi/MEKi combination therapy who developed an acneiform eruption after treatment discontinuation rather than during active therapy.
We present the case of a 67 year old Caucasian male that was initially treated with BRAF inhibitors followed by anti-CTLA4 and then anti-PD1 immunotherapy for metastatic melanoma but later developed colorectal cancer.
We describe peripheral blood smear, bone marrow morphology, histopathology, immunohistochemistry, including BRAFV600E, and molecular testing results of patients with metastatic melanoma to the bone marrow.
We report the case of a 62-year-old female with metastatic melanoma who developed primary cutaneous small/medium CD4 T-cell lymphoproliferative disorder (PC-SMTCL) after treatment with vemurafenib and recombinant high-dose interleukin-2 (IL-2).