Biology and Treatment Advances in Cutaneous Squamous Cell Carcinoma

Thai, Alesha; Lim, Annette; Solomon, Benjamin; Rischin, Danny

doi:10.3390/cancers13225645

“…Although the NCCN guidelines for cSCC provide a framework for stratifying patients, the heterogeneous nature of the disease has made accurate risk assessment by use of clinicopathologic factors alone challenging and incomplete. 48,49 Furthermore, evaluating subjective clinicopathologic factors like "degree of differentiation" or "rapidly growing tumor", having multiple measurements of depth of invasion (Breslow depth or Clark level) and even considering of the wide spectrum of patients deemed immunosuppressed, have further created uncertainty in the field. 31,[50][51][52] Currently, the use of multidisciplinary tumor boards (MDTBs) are known to improve outcomes in managing several malignancies.…”

Section: Discussionmentioning

confidence: 99%

Incorporation of the 40-Gene Expression Profile (40-GEP) Test to Improve Treatment Decisions in High-Risk Cutaneous Squamous Cell Carcinoma (cSCC) Patients: Case Series and Algorithm

Singh¹,

Tolkachjov²,

Farberg³

2023

CCID

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Cutaneous squamous cell carcinoma (cSCC) has become a significant public health issue due to its rapidly rising incidence and an estimated 1.8 million newly diagnosed cases annually. As with other cancers, treatment decisions for patients with cSCC are based primarily on a patient's risk for poor outcomes. There has been improvement in clinicopathologic factor-based risk assessment approaches, either through informal methods or ever evolving staging approaches. However, these approaches misidentify patients who will eventually have disease progression as low-risk and conversely, over classify patients as high-risk who do not experience relapse. To improve the accuracy of risk assessment for patients with cSCC, the 40-gene expression profile (40-GEP) test has been validated to show statistically significant stratification of a high-risk cSCC patient's risk of nodal or distant metastasis, independent of currently available risk-assessment methods. The 40-GEP test allows for a more accurate classification of metastatic risk for high-risk cSCC patients, with the aim to influence appropriate allocation of clinician time and therapeutic resources to those patients who will most benefit. The objective of this article is to present a treatment algorithm in which clinicians can easily integrate the results of the 40-GEP test into their current treatment approaches to tailor patient care based on individual tumor biology. The following modalities were considered: surveillance imaging, sentinel lymph node biopsy (SLNB), adjuvant radiation therapy (ART), and clinical follow-up. The authors have contributed their own cases for discussion as to how they have seen the beneficial impact of 40-GEP test results in their own practice. Overall, clinicians can identify risk-aligned treatment pathway improvements with the use of the 40-GEP test for challenging to manage, high-risk cSCC patients.

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“…We conducted treatment experiments to study whether the novel cSCC-PDX responds to chemotherapy (Fig. 5 ) 23 – 25 . Regarding cytotoxic chemotherapies, the xenografted model responded well to cisplatin, which has been reported to be the standard medication 24 , 25 .…”

Section: Resultsmentioning

confidence: 99%

Eribulin inhibits growth of cutaneous squamous cell carcinoma cell lines and a novel patient-derived xenograft

Hsu

¹

,

Yanagi

²

,

Maeda

³

et al. 2023

Sci Rep

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Advanced cutaneous squamous cell carcinoma (cSCC) is treated with chemotherapy and/or radiotherapy, but these typically fail to achieve satisfactory clinical outcomes. There have been no preclinical studies to evaluate the effectiveness of eribulin against cSCC. Here, we examine the effects of eribulin using cSCC cell lines and a novel cSCC patient-derived xenograft (PDX) model. In the cSCC cell lines (A431 and DJM-1 cells), eribulin was found to inhibit tumor cell proliferation in vitro as assessed by cell ATP levels. DNA content analysis by fluorescence-activated cell sorting (FACS) showed that eribulin induced G2/M cell cycle arrest and apoptosis. In xenograft models of cSCC cell lines, the administration of eribulin suppressed tumor growth in vivo. We also developed a cSCC patient-derived xenograft (PDX) which reproduces the histological and genetic characteristics of a primary tumor. Pathogenic mutations in TP53 and ARID2 were detected in the patient’s metastatic tumor and in the PDX tumor. The cSCC-PDX responded well to the administration of eribulin and cisplatin. In conclusion, the present study shows the promising antineoplastic effects of eribulin in cSCC. Also, we established a novel cSCC-PDX model that preserves the patient’s tumor. This PDX could assist researchers who are exploring innovative therapies for cSCC.

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“…We conducted treatment experiments to study whether the novel cSCC-PDX responds to chemotherapy (Fig. 5) [23][24][25] . Regarding cytotoxic chemotherapies, the xenografted model responded well to cisplatin, which has been reported to be the standard medication 24,25 .…”

Section: Eribulin Suppresses Tumor Growth In the Novel Cscc-pdx Mouse...mentioning

confidence: 99%

“…5) [23][24][25] . Regarding cytotoxic chemotherapies, the xenografted model responded well to cisplatin, which has been reported to be the standard medication 24,25 . Furthermore, we administrated eribulin monotherapy, which has proven effective as a second-line treatment for metastatic breast cancer 26 .…”

Section: Eribulin Suppresses Tumor Growth In the Novel Cscc-pdx Mouse...mentioning

confidence: 99%

Eribulin inhibits growth of cutaneous squamous cell carcinoma cell lines and a novel patient-derived xenograft

Hsu

¹

,

Yanagi

²

,

Maeda

³

et al. 2023

Preprint

View full text Add to dashboard Cite

Advanced cutaneous squamous cell carcinoma (cSCC) is treated with chemotherapy and/or radiotherapy, but these typically fail to achieve satisfactory clinical outcomes. There have been no preclinical studies to evaluate the effectiveness of eribulin against cSCC. Here, we examine the effects of eribulin using cSCC cell lines and a novel cSCC patient-derived xenograft (PDX) model. In the cSCC cell lines (A431 and DJM-1 cells), eribulin was found to inhibit tumor cell proliferation in vitro as assessed by cell ATP levels. DNA content analysis by fluorescence-activated cell sorting (FACS) showed that eribulin induced G2/M cell cycle arrest and apoptosis. In xenograft models of cSCC cell lines, the administration of eribulin suppressed tumor growth in vivo. We also developed a cSCC patient-derived xenograft (PDX) which reproduces the histological and genetic characteristics of a primary tumor. Pathogenic mutations in TP53 and ARID2 were detected in the patient’s metastatic tumor and in the PDX tumor. The cSCC-PDX responded well to the administration of eribulin and cisplatin. In conclusion, the present study shows the promising antineoplastic effects of eribulin in cSCC. Also, we established a novel cSCC-PDX model that preserves the patient’s tumor. This PDX could assist researchers who are exploring innovative therapies for cSCC.

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Biology and Treatment Advances in Cutaneous Squamous Cell Carcinoma

Cited by 7 publications

References 188 publications

Incorporation of the 40-Gene Expression Profile (40-GEP) Test to Improve Treatment Decisions in High-Risk Cutaneous Squamous Cell Carcinoma (cSCC) Patients: Case Series and Algorithm

Incorporation of the 40-Gene Expression Profile (40-GEP) Test to Improve Treatment Decisions in High-Risk Cutaneous Squamous Cell Carcinoma (cSCC) Patients: Case Series and Algorithm

Eribulin inhibits growth of cutaneous squamous cell carcinoma cell lines and a novel patient-derived xenograft

Eribulin inhibits growth of cutaneous squamous cell carcinoma cell lines and a novel patient-derived xenograft

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