Characterization and management of ERK inhibitor associated dermatologic adverse events: analysis from a nonrandomized trial of ulixertinib for advanced cancers

Wu, Jennifer; Liu, D.; Offin, Michael; Lezcano, Cecilia; Torrisi, Jean; Brownstein, Sheldon L.; Hyman, David M.; Gounder, Mrinal M.; Abida, Wassim; Drilon, Alexander; Harding, James J.; Sullivan, Ryan J.; Janků, Filip; Welsch, Dean J.; Varterasian, Mary; Groover, Anna; Li, B. T.; Lacouture, Mario E.

doi:10.1007/s10637-020-01035-9

Cited by 17 publications

(13 citation statements)

References 61 publications

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“…Although there are currently no FDA-approved inhibitors targeting ERK, the recognition that ERK reactivation arises in resistant cancers following prolonged treatment with RAF and MEK inhibitors has generated renewed interest in targeting ERK (see Section 2.7 ). Selective ERK1/2 inhibitors, including BVD-523, LY3214996, and ASTX-029, are currently under preclinical and clinical evaluation for various solid cancers with RAS or RAF mutations [ 33 , 139 , 146 , 147 , 148 ]. In particular, BVD-523 showed anti-proliferative activity in cell lines of colorectal and pancreatic cancers with B-RAF and K-RAS mutations, respectively [ 149 , 150 ].…”

Section: Mapk/erk Signaling Pathway In Hccmentioning

confidence: 99%

MAPK/ERK Signaling Pathway in Hepatocellular Carcinoma

Moon

2021

Cancers

126

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Hepatocellular carcinoma (HCC) is a major health concern worldwide, and its incidence is increasing steadily. Recently, the MAPK/ERK signaling pathway in HCC has gained renewed attention from basic and clinical researchers. The MAPK/ERK signaling pathway is activated in more than 50% of human HCC cases; however, activating mutations in RAS and RAF genes are rarely found in HCC, which are major genetic events leading to the activation of the MAPK/ERK signaling pathway in other cancers. This suggests that there is an alternative mechanism behind the activation of the signaling pathway in HCC. Here, we will review recent advances in understanding the cellular and molecular mechanisms involved in the activation of the MAPK/ERK signaling pathway and discuss potential therapeutic strategies targeting the signaling pathway in the context of HCC.

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Section: Mapk/erk Signaling Pathway In Hccmentioning

confidence: 99%

MAPK/ERK Signaling Pathway in Hepatocellular Carcinoma

Moon

2021

Cancers

126

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“…7,21,22 It should also be noted that photosensitivity reactions have also been recently reported with newly-developed targeted anticancer therapies. [23][24][25][26] Finally, the majority of the targeted anticancer therapies inhibiting c-KIT may induce progressive depigmentation of the skin and/or hair, which may lead to exacerbated sensitivity after UV-exposure in treated patients. [27][28][29] Selective BRAF inhibitor vemurafenib Vemurafenib, a first-in-class BRAF inhibitor, is used either alone or in combination with the mitogen-activated protein kinase (MEK) inhibitor cobimetinib for the treatment of patients with advanced BRAF V600-mutant melanoma.…”

Section: Targeted Anticancer Therapiesmentioning

confidence: 99%

“…In particular, photosensitive reactions may occur in 3%-9% of patients. 26 These reports highlight the need for ongoing surveillance of the cutaneous AEs associated with newly-developed targeted anticancer therapies. JEADV 2022, 36 (Suppl.…”

Section: Ret Inhibitor Vandetanibmentioning

confidence: 99%

“…Vemurafenib and vandetanib are the two targeted anticancer therapies for which phototoxicity has been noted as a common dermatologic AE 7,21,22 . It should also be noted that photosensitivity reactions have also been recently reported with newly‐developed targeted anticancer therapies 23–26 . Finally, the majority of the targeted anticancer therapies inhibiting c‐KIT may induce progressive depigmentation of the skin and/or hair, which may lead to exacerbated sensitivity after UV‐exposure in treated patients 27–29 …”

Section: Targeted Anticancer Therapiesmentioning

confidence: 99%

“…Finally, ulixertinib, a first‐in‐class ERK (extracellular signal‐regulated kinase) 1/2 inhibitor with clinical activity in BRAF‐ and NRAS‐mutant cancers, has been associated with the development of skin toxicities in more than 75% of cases. In particular, photosensitive reactions may occur in 3%–9% of patients 26 …”

Section: Targeted Anticancer Therapiesmentioning

confidence: 99%

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Anticancer treatments and photosensitivity

Sibaud

2022

Acad Dermatol Venereol

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Drug‐induced photosensitivity is associated with a wide range of anticancer treatments, including conventional chemotherapeutic agents, targeted anticancer therapies, and immune checkpoint inhibitors. These dermatologic adverse events can have a major impact on the well‐being and quality of life of cancer patients, leading to dose modifications and interruption or discontinuation of anticancer treatments in severe cases. However, the heterogeneous nature of the photosensitive reactions induced by these agents, as well as the common concomitant use of other potentially photosensitizing drugs (antibiotics, voriconazole, nonsteroidal anti‐inflammatory drugs, etc.), can make the diagnosis and, therefore the prevention, of these adverse events particularly challenging. The aim of this review is to describe the most characteristic forms of photosensitivity observed in patients being treated with anticancer treatments, including phototoxicity and photoallergy, and other potentially photo‐induced manifestations such as UV recall, exaggerated sunburn reactions associated with treatment‐related vitiligo, drug‐induced cutaneous lupus erythematosus, and UV‐induced hyperpigmentation. We also discuss the photosensitive reactions recently reported with new‐generation targeted anticancer therapies and immune checkpoint inhibitors and highlight the importance of continued surveillance to identify photosensitizing agents, and of educating patients on the need for preventive UVA/UVB photoprotective measures.

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