Concomitant cetuximab and radiation therapy: A possible promising strategy for locally advanced inoperable non-melanoma skin carcinomas

Scarpati, Giuseppina Della Vittoria; Perri, Francesco; Pisconti, Salvatore; Costa, Giuseppe; Ricciardiello, Filippo; Prete, Salvatore Del; Napolitano, Alberto; Carraturo, Marco; Mazzone, Salvatore; Addeo, Raffaele

doi:10.3892/mco.2016.746

Cited by 18 publications

(15 citation statements)

References 46 publications

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“…Infrequently, patients present with barriers to surgery or disease not amenable to surgical resection, and for these patients new treatments must be sought. Furthermore, the pathophysiology of locally advanced cSCC (LA‐cSCC) may make complete surgical resection challenging, as these patients often present with extensive local invasion and/or with nodal metastases . In cases where disease is inoperable, or for patients for whom surgery would not be possible for medical reasons, radiotherapy alone or concurrent chemoradiation may be considered as a treatment alternative.…”

Section: Introductionmentioning

confidence: 99%

Cetuximab‐radiotherapy combination in the management of locally advanced cutaneous squamous cell carcinoma

et al. 2018

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Introduction:We report the outcomes of using a combination of cetuximab with radiation therapy (Cetux-RT) to treat a selected group of patients with locally advanced (unresectable) cutaneous squamous cell carcinoma (LA-cSCC). This study presents two-year efficacy and safety data for 8 patients with LA-cSCC treated within a single institution. Methods: Between 2014 and 2017 a total of eight patients (seven males, one female) with LA-cSCC received curative intent treatment with Cetux-RT. All patients received an initial loading dose of cetuximab at 400 mg/m 2 seven days prior to radiotherapy, followed by weekly treatment with 250 mg/m 2 , continuing through the end of radiotherapy. Radiation doses were 6600 cGy/ 30 fr (n = 2), 6300 cGy/30fr (n = 2) and 5500 cGy/22 fr (n = 4). Results: The median age was 81 years (range, 55-87). The ECOG performance status of all patients was between 0 and 2. With a median duration of followup of 25 months (range 10-48 months), five patients remain in a complete response. After a partial response, another patient has relapsed and is receiving palliative chemotherapy, while two patients have died during the period of follow up (one of whom died following progression of disease, the other of an unrelated cause). Treatment in this group of patients was well tolerated, with most toxicities ≤ grade 2, and no toxicities of grade 4/5 reported. Conclusions: Cetux-RT was well tolerated and provided durable disease control within this patient sample. Our data support the use of the Cetux-RT regimen for selected patients with inoperable LA-cSCC and adequate performance status.

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Section: Introductionmentioning

confidence: 99%

Cetuximab‐radiotherapy combination in the management of locally advanced cutaneous squamous cell carcinoma

et al. 2018

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“…Treatment with gefitinib, an EGFR inhibitor, in combination with either cyclopamine or GANT61 reduced cell growth of BCC cell line more effectively than any of the agents individually . Cetuximab, a monoclonal antibody inhibits EGFR and has shown potential in targeting NMSC . It may also be evaluated for the treatment of advanced BCCs along with HH pathway inhibitors …”

Section: Interventionsmentioning

confidence: 99%

“…Cetuximab, a monoclonal antibody inhibits EGFR and has shown potential in targeting NMSC . It may also be evaluated for the treatment of advanced BCCs along with HH pathway inhibitors …”

Section: Interventionsmentioning

confidence: 99%

“…13 Cetuximab, a monoclonal antibody inhibits EGFR and has shown potential in targeting NMSC. 187 It may also be evaluated for the treatment of advanced BCCs along with HH pathway inhibitors. 187 Crosstalk involving PI3K and SHH has been linked with acquired resistance to SMO inhibition.…”

Section: Combination Therapiesmentioning

confidence: 99%

“…187 It may also be evaluated for the treatment of advanced BCCs along with HH pathway inhibitors. 187 Crosstalk involving PI3K and SHH has been linked with acquired resistance to SMO inhibition. 188 Thus, combination therapy involving PI3K/mTOR inhibition along with HH inhibition may be an effective therapeutic strategy.…”

Section: Combination Therapiesmentioning

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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Applications of SNAP‐tag technology in skin cancer therapy

Padayachee

Adeola

Wyk

et al. 2019

Health Science Reports

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Background Cancer treatment in the 21st century has seen immense advances in optical imaging and immunotherapy. Significant progress has been made in the bioengineering and production of immunoconjugates to achieve the goal of specifically targeting tumors. Discussion In the 21st century, antibody drug conjugates (ADCs) have been the focus of immunotherapeutic strategies in cancer. ADCs combine the unique targeting of monoclonal antibodies (mAbs) with the cancer killing ability of cytotoxic drugs. However, due to random conjugation methods of drug to antibody, ADCs are associated with poor antigen specificity and low cytotoxicity, resulting in a drug to antibody ratio (DAR) >1. This means that the cytotoxic drugs in ADCs are conjugated randomly to antibodies, by cysteine or lysine residues. This generates heterogeneous ADC populations with 0 to 8 drugs per an antibody, each with distinct pharmacokinetic, efficacy, and toxicity properties. Additionally, heterogeneity is created not only by different antibody to ligand ratios but also by different sites of conjugation. Hence, much effort has been made to find and establish antibody conjugation strategies that enable us to better control stoichiometry and site‐specificity. This includes utilizing protein self‐labeling tags as fusion partners to the original protein. Site‐specific conjugation is a significant characteristic of these engineered proteins. SNAP‐tag is one such engineered self‐labeling protein tag shown to have promising potential in cancer treatment. The SNAP‐tag is fused to an antibody of choice and covalently reacts specifically in a 1:1 ratio with benzylguanine (BG) substrates, eg, fluorophores or photosensitizers, to target skin cancer. This makes SNAP‐tag a versatile technique in optical imaging and photoimmunotherapy of skin cancer. Conclusion SNAP‐tag technology has the potential to contribute greatly to a broad range of molecular oncological applications because it combines efficacious tumor targeting, minimized local and systemic toxicity, and noninvasive assessment of diagnostic/prognostic molecular biomarkers of cancer.

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Concomitant cetuximab and radiation therapy: A possible promising strategy for locally advanced inoperable non-melanoma skin carcinomas

Cited by 18 publications

References 46 publications

Cetuximab‐radiotherapy combination in the management of locally advanced cutaneous squamous cell carcinoma

Cetuximab‐radiotherapy combination in the management of locally advanced cutaneous squamous cell carcinoma

Basal cell carcinoma pathogenesis and therapy involving hedgehog signaling and beyond

Applications of SNAP‐tag technology in skin cancer therapy

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