Incidental regression of an advanced basal cell carcinoma after ipilimumab exposure for metastatic melanoma

Mohan, Shalini; Kuo, Karen Y.; Chang, Anne Lynn S.

doi:10.1016/j.jdcr.2015.11.007

Cited by 34 publications

(20 citation statements)

References 4 publications

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“…A case report has shown incidental regression of an advanced basal carcinoma in a patient with metastatic melanoma being treated with ipilimumab, a cytotoxic T-lymphocyte associated protein-4 (CTLA-4) antagonist, implying that these tumours can be responsive to checkpoint inhibition. 17 Recently, Winkler et al . 18 reported on a patient with metastatic basal cell carcinoma whose best response to treatment with pembrolizumab was stable disease for a few months.…”

Section: Discussionmentioning

confidence: 99%

Metastatic basal cell carcinoma with amplification of PD-L1: exceptional response to anti-PD1 therapy

et al. 2016

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Metastatic basal cell carcinomas are rare malignancies harbouring Hedgehog pathway alterations targetable by SMO antagonists (vismodegib/sonidegib). We describe, for the first time, the molecular genetics and response of a patient with Hedgehog inhibitor-resistant metastatic basal cell carcinoma who achieved rapid tumour regression (ongoing near complete remission at 4 months) with nivolumab (anti-PD1 antibody). He had multiple hallmarks of anti-PD1 responsiveness including high mutational burden (> 50 mutations per megabase; 19 functional alterations in tissue next-generation sequencing (NGS; 315 genes)) as well as PDL1/PDL2/JAK2 amplification (as determined by both tissue NGS and by analysis of plasma-derived cell-free DNA). The latter was performed using technology originally developed for the genome-wide detection of sub-chromosomal copy-number alterations (CNAs) in noninvasive prenatal testing and showed numerous CNAs including amplification of the 9p24.3-9p22.2 region containing PD-L1, PD-L2 and JAK2. Of interest, PD-L1, PD-L2 and JAK2 amplification is a characteristic of Hodgkin lymphoma, which is exquisitely sensitive to nivolumab. In conclusion, selected SMO antagonist-resistant metastatic basal cell carcinomas may respond to nivolumab based on underlying molecular genetic mechanisms that include PD-L1 amplification and high tumour mutational burden.

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Section: Discussionmentioning

confidence: 99%

Metastatic basal cell carcinoma with amplification of PD-L1: exceptional response to anti-PD1 therapy

et al. 2016

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“…Treatment for recurrent nodular melanoma with ipilimumab incidentally also led to the regression of concurrent advanced BCC . This surprising finding suggests that impilimumab may be an effective agent to counter CTLA‐4 mediated immunotherapy in BCCs …”

Section: Interventionsmentioning

confidence: 98%

“…169,170 Treatment for recurrent nodular melanoma with ipilimumab incidentally also led to the regression of concurrent advanced BCC. 171 This surprising finding suggests that impilimumab may be an effective agent to counter CTLA-4 mediated immunotherapy in BCCs. 171 The inflammatory response produced by COX-2 induced prostaglandins appears important in the development of BCC.…”

Section: Immunotherapymentioning

confidence: 99%

“…171 This surprising finding suggests that impilimumab may be an effective agent to counter CTLA-4 mediated immunotherapy in BCCs. 171 The inflammatory response produced by COX-2 induced prostaglandins appears important in the development of BCC. COX-2 overexpression, induced by ROS following UV exposure could be linked with BCC tumor proliferation and promotion at least in part.…”

Section: Immunotherapymentioning

confidence: 99%

“…CTLA‐4 blocking antibodies such as, ipilimumab, promote T‐cell recognition of tumors such as melanoma and nonsmall cell lung cancer . Treatment for recurrent nodular melanoma with ipilimumab incidentally also led to the regression of concurrent advanced BCC . This surprising finding suggests that impilimumab may be an effective agent to counter CTLA‐4 mediated immunotherapy in BCCs …”

Section: Interventionsmentioning

confidence: 99%

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Basal cell carcinoma pathogenesis and therapy involving hedgehog signaling and beyond

Bakshi

Chaudhary

Rana

et al. 2017

Molecular Carcinogenesis

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Basal cell carcinoma (BCC) of the skin is driven by aberrant hedgehog signaling. Thus blocking this signaling pathway by small molecules such as vismodegib inhibits tumor growth. Primary cilium in the epidermal cells plays an integral role in the processing of hedgehog signaling-related proteins. Recent genomic studies point to the involvement of additional genetic mutations that might be associated with the development of BCCs, suggesting significance of other signaling pathways, such as WNT, NOTCH, mTOR, and Hippo, aside from hedgehog in the pathogenesis of this human neoplasm. Some of these pathways could be regulated by noncoding microRNA. Altered microRNA expression profile is recognized with the progression of these lesions. Stopping treatment with Smoothened (SMO) inhibitors often leads to tumor reoccurrence in the patients with basal cell nevus syndrome, who develop 10–100 of BCCs. In addition, the initial effectiveness of these SMO inhibitors is impaired due to the onset of mutations in the drug-binding domain of SMO. These data point to a need to develop strategies to overcome tumor recurrence and resistance and to enhance efficacy by developing novel single agent-based or multiple agents-based combinatorial approaches. Immunotherapy and photodynamic therapy could be additional successful approaches particularly if developed in combination with chemotherapy for inoperable and metastatic BCCs.

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Immunotherapy for Basal Cell Carcinoma

Chen

Silapunt

Migden

2019

Basal Cell Carcinoma

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Incidental regression of an advanced basal cell carcinoma after ipilimumab exposure for metastatic melanoma

Cited by 34 publications

References 4 publications

Metastatic basal cell carcinoma with amplification of PD-L1: exceptional response to anti-PD1 therapy

Metastatic basal cell carcinoma with amplification of PD-L1: exceptional response to anti-PD1 therapy

Basal cell carcinoma pathogenesis and therapy involving hedgehog signaling and beyond

Immunotherapy for Basal Cell Carcinoma

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