Efficacy and safety of single-agent pan-human epidermal growth factor receptor (HER) inhibitor dacomitinib in locally advanced unresectable or metastatic skin squamous cell cancer

Cavalieri, Stefano; Perrone, Federica; Miceli, Rosalba; Ascierto, Paolo A.; Locati, Laura D.; Bergamini, Cristiana; Granata, Roberta; Alfieri, Salvatore; Resteghini, Carlo; Galbiati, Donata; Busico, Adele; Paielli, Nicholas; Patuzzo, Roberto; Maurichi, Andrea; Gallino, Gianfrancesco; Ruggeri, Roberta; Mariani, Luigi; Palla, Marco; Licitra, Lisa; Bossi, Paolo

doi:10.1016/j.ejca.2018.04.004

Cited by 39 publications

(33 citation statements)

References 26 publications

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“…The genetic alterations found in HNSCC are commonly found in other tumor types, and therapies targeting some of these specific mutations exist. Regardless, with the exception of cetuximab, an anti-EGFR antibody that is used in treatment of HNSCC, no targeted therapies are currently applied in standard care of these patients (43)(44)(45)(46). In recent years, it has become clear that mutation status alone does not provide the required specificity or sensitivity to serve as a predictive marker (47).…”

Section: Hnscc Tumoroids As a Platform For Drug Screeningmentioning

confidence: 99%

Oral Mucosal Organoids as a Potential Platform for Personalized Cancer Therapy

et al. 2019

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Previous studies have described that tumor organoids can capture the diversity of defined human carcinoma types. Here, we describe conditions for long-term culture of human mucosal organoids. Using this protocol, a panel of 31 head and neck squamous cell carcinoma (HNSCC)-derived organoid lines was established. This panel recapitulates genetic and molecular characteristics previously described for HNSCC. Organoids retain their tumorigenic potential upon xenotransplantation. We observe differential responses to a panel of drugs including cisplatin, carboplatin, cetuximab, and radiotherapy in vitro. Additionally, drug screens reveal selective sensitivity to targeted drugs that are not normally used in the treatment of patients with HNSCC. These observations may inspire a personalized approach to the management of HNSCC and expand the repertoire of HNSCC drugs. SIGNIFICANCE: This work describes the culture of organoids derived from HNSCC and corresponding normal epithelium. These tumoroids recapitulate the disease genetically, histologically, and functionally. In vitro drug screening of tumoroids reveals responses to therapies both currently used in the treatment of HNSCC and those not (yet) used in clinical practice.

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Section: Hnscc Tumoroids As a Platform For Drug Screeningmentioning

confidence: 99%

Oral Mucosal Organoids as a Potential Platform for Personalized Cancer Therapy

et al. 2019

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“…Mutational data were obtained by targeted next‐generation sequencing (T‐NGS) using the Ion AmpliSeq Cancer Hotspot Panel v2 (Life Technologies, Carlsbad, CA, USA) with the Ion‐Torrent Personal Genome Machine platform (Life Technologies) . Library preparation, emulsion polymerase chain reaction (PCR) and chip loading were performed as previously described . Data were processed by using Torrent Suite and variants were analyzed as previously described .…”

Section: Methodsmentioning

confidence: 99%

“…16 Library preparation, emulsion polymerase chain reaction (PCR) and chip loading were performed as previously described. 17 Data were processed by using Torrent Suite and variants were analyzed as previously described. 16 We looked at molecular alterations, which could potentially pave the way for targeted therapeutic approaches, and we leveraged on the alterations already reported in salivary gland cancer and basal cell carcinoma whose histological profiles could resemble the ones of SAC.…”

Section: Targeted Next-generation Sequencingmentioning

confidence: 99%

Identification of potentially druggable molecular alterations in skin adnexal malignancies

Cavalieri

Busico

Capone

et al. 2019

The Journal of Dermatology

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Skin adnexal cancers (SAC) are a heterogeneous group of rare malignancies with histological differentiation towards epithelial adnexa, which lack effective systemic treatments. The aim of this work is to identify any potentially druggable genomic alterations for possible targeted therapies. Cases of primary or recurrent/metastatic (RM) SAC between 2002 and 2014 were identified by searching the institutional cancer registration database. Histological sections of all referral cases were reviewed by a dedicated pathologist to confirm diagnosis. Immunohistochemistry was performed to assess the expression of androgen receptors (AR) and human epidermal growth factor receptor type 2 (HER2). Targeted next‐generation sequencing (T‐NGS) was performed to identify targetable mutations (panel of 50 genes analyzed by Cancer Hotspot Panel, Ion‐Torrent Personal Genome Machine). Mutational analysis of the PTCH1 gene not present in the T‐NGS panel was assessed by Sanger sequencing. A total of 45 cases with available histological samples were identified (35 primary, 10 RM). The most frequent histological type was porocarcinoma (n = 12). Globally, 14 cases (31%) were AR+ (6/10 RM, 60%; 8/35 primary, 23%). HER2 was shown as 2+ in eight of 42 (19%) cases (2/9 RM, 22%; 6/33 primary, 18%). DNA was adequate for T‐NGS analysis in 25 cases. In the majority of cases (17 cases, 68%) at least one mutation in oncogenes or tumor suppressor genes was found: the most frequent ones involved TP.53 (13 cases, 76% of mutated SAC) and PIK3CA (three cases, 18%). The rate of PTCH1 mutation was 30%. These findings support the use of molecular screening in patients with advanced SAC.

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“…The objective response rate of 28% is reported for Cetuximab, an EGFR inhibitor [1], and objective response rates in a range of 10-31% are reported for the administration of other drugs associated with inhibition of EGFR such as dacomitinib, erlotinib, and panitumumab [1,17]. Moreover, a mean overall survival of 8.1 months in a phase 2 study of cetuximab in patients with advanced cutaneous SCC was reported [4]. This low response rate and short mean overall survival time show the low efficacy of common therapies.…”

Section: Cutaneous Sccmentioning

confidence: 99%

“…The most common therapeutic regimens are chemotherapy and epidermal growth factor receptor (EGFR) inhibitors [1][2][3]. However, some studies have reported the low efficacy of cytotoxic chemotherapies (cisplatin, 5-fluorouracil (5-FU), bleomycin, and doxorubicin) and EGFR inhibitors [4,5]. Due to the fact that cutaneous SCC in the advanced stage has limited response to common therapies, investigations into systematic therapies with better response rates are crucial [6,7].…”

Section: Introductionmentioning

confidence: 99%