RESUMO
As one of the most common malignancies, basal cell carcinoma (BCC) has evolved as a global burden with incidence annually rising, especially in the older population. Even though the condition is mostly localized, the nature of the disease is destructive and can evolve as either locally advanced BCC (laBCC) or even more rarely as metastatic BCC (mBCC). There are well-established conventional treatment options for these cases, including surgeries and radiotherapy. However, not all cases are eligible for conventional treatments. Recently, biologic treatment has gained a lot of attention and research. This has led to the development of targeted treatment involving the hedgehog pathway inhibitor (HPI), a key pathogenesis in laBCC and mBCC. There are currently two approved HPIs, vismodegib and sonidegib to treat inoperable laBCC and mBCC. This review seeks to explore the pathophysiology of hedgehog pathway behind the development of BCC, and the current update of the efficacy as well as pharmacokinetics properties of HPIs that led to the ideal treatment for laBCC or mBCC, either as monotherapy or in combination with other conventional therapies.
Assuntos
Antineoplásicos , Carcinoma Basocelular , Neoplasias Cutâneas , Anilidas/efeitos adversos , Antineoplásicos/efeitos adversos , Compostos de Bifenilo , Carcinoma Basocelular/tratamento farmacológico , Carcinoma Basocelular/patologia , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/uso terapêutico , Humanos , Piridinas , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologiaRESUMO
El carcinoma de células basales (CBC) es una de las neoplasias malignas más frecuentes, por lo que se ha convertido en una importante carga asistencial. Su incidencia se incrementa anualmente, especialmente en la población con mayor edad. A pesar de que generalmente está bien localizado, el CBC tiene la capacidad de destruir tejidos y evolucionar a un CBC localmente avanzado (CBCla) o incluso, aunque de forma más rara, a un CBC metastásico (CBCm). Las opciones terapéuticas convencionales en estos casos están bien establecidas, entre las cuales se incluyen la cirugía y la radioterapia. Sin embargo, no todos los casos son elegibles para realizar un tratamiento de tipo convencional. Recientemente, los tratamientos biológicos vienen ganando una mayor atención y son objeto de diversos estudios de investigación. De este modo se ha desarrollado una terapia dirigida utilizando los inhibidores de la vía de Hedgehog (IVH), teniendo en cuenta que se trata de una vía patogénica clave tanto en el CBCla como en el CBCm. En la actualidad, para poder tratar el CBCla y el CBCm no operables existen dos IVH aprobados: el vismodegib y el sonidegib. Esta revisión busca explorar la fisiopatología de la vía del Hedgehog responsable del desarrollo del CBC y hacer una actualización en cuanto a la eficacia, así como de las propiedades farmacocinéticas de los IVH, características que los convirtieron en la opción terapéutica ideal en el CBCla o en el CBCm, ya sea en forma de monoterapia o en combinación con alguno de los tratamientos convencionales (AU)
As one of the most common malignancies, basal cell carcinoma (BCC) has evolved as a global burden with incidence annually rising, especially in the older population. Even though the condition is mostly localized, the nature of the disease is destructive and can evolve as either locally advanced BCC (laBCC) or even more rarely as metastatic BCC (mBCC). There are well-established conventional treatment options for these cases, including surgeries and radiotherapy. However, not all cases are eligible for conventional treatments. Recently, biologic treatment has gained a lot of attention and research. This has led to the development of targeted treatment involving the hedgehog pathway inhibitor (HPI), a key pathogenesis in laBCC and mBCC. There are currently two approved HPIs, vismodegib and sonidegib to treat inoperable laBCC and mBCC. This review seeks to explore the pathophysiology of hedgehog pathway behind the development of BCC, and the current update of the efficacy as well as pharmacokinetics properties of HPIs that led to the ideal treatment for laBCC or mBCC, either as monotherapy or in combination with other conventional therapies (AU)
Assuntos
Humanos , Antineoplásicos/uso terapêutico , Neoplasia de Células Basais/tratamento farmacológico , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/antagonistas & inibidores , Neoplasias Cutâneas/tratamento farmacológico , Neoplasia de Células Basais/fisiopatologia , Neoplasias Cutâneas/fisiopatologiaRESUMO
As one of the most common malignancies, basal cell carcinoma (BCC) has evolved as a global burden with incidence annually rising, especially in the older population. Even though the condition is mostly localized, the nature of the disease is destructive and can evolve as either locally advanced BCC (laBCC) or even more rarely as metastatic BCC (mBCC). There are well-established conventional treatment options for these cases, including surgeries and radiotherapy. However, not all cases are eligible for conventional treatments. Recently, biologic treatment has gained a lot of attention and research. This has led to the development of targeted treatment involving the hedgehog pathway inhibitor (HPI), a key pathogenesis in laBCC and mBCC. There are currently two approved HPIs, vismodegib and sonidegib to treat inoperable laBCC and mBCC. This review seeks to explore the pathophysiology of hedgehog pathway behind the development of BCC, and the current update of the efficacy as well as pharmacokinetics properties of HPIs that led to the ideal treatment for laBCC or mBCC, either as monotherapy or in combination with other conventional therapies (AU)
El carcinoma de células basales (CBC) es una de las neoplasias malignas más frecuentes, por lo que se ha convertido en una importante carga asistencial. Su incidencia se incrementa anualmente, especialmente en la población con mayor edad. A pesar de que generalmente está bien localizado, el CBC tiene la capacidad de destruir tejidos y evolucionar a un CBC localmente avanzado (CBCla) o incluso, aunque de forma más rara, a un CBC metastásico (CBCm). Las opciones terapéuticas convencionales en estos casos están bien establecidas, entre las cuales se incluyen la cirugía y la radioterapia. Sin embargo, no todos los casos son elegibles para realizar un tratamiento de tipo convencional. Recientemente, los tratamientos biológicos vienen ganando una mayor atención y son objeto de diversos estudios de investigación. De este modo se ha desarrollado una terapia dirigida utilizando los inhibidores de la vía de Hedgehog (IVH), teniendo en cuenta que se trata de una vía patogénica clave tanto en el CBCla como en el CBCm. En la actualidad, para poder tratar el CBCla y el CBCm no operables existen dos IVH aprobados: el vismodegib y el sonidegib. Esta revisión busca explorar la fisiopatología de la vía del Hedgehog responsable del desarrollo del CBC y hacer una actualización en cuanto a la eficacia, así como de las propiedades farmacocinéticas de los IVH, características que los convirtieron en la opción terapéutica ideal en el CBCla o en el CBCm, ya sea en forma de monoterapia o en combinación con alguno de los tratamientos convencionales (AU)
Assuntos
Humanos , Antineoplásicos/uso terapêutico , Neoplasia de Células Basais/tratamento farmacológico , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/antagonistas & inibidores , Neoplasias Cutâneas/tratamento farmacológico , Neoplasia de Células Basais/fisiopatologia , Neoplasias Cutâneas/fisiopatologiaRESUMO
Internal carotid artery (ICA) pseudoaneurysm formation following transsphenoidal surgery is a rare but potentially lethal complication. Direct surgical repair with preservation of the ICA may be difficult. The feasibility of endovascular coil embolization with parent artery preservation for an iatrogenic ICA pseudoaneurysm is undefined. A 40-year-old man was referred to the authors' institution after identification of a pseudoaneurysm of the left ICA following transsphenoidal resection of a pituitary macroadenoma. The pseudoaneurysm was treated via an endovascular approach that included stent-assisted coil embolization of the lesion. Follow-up angiographic studies obtained 1 year later demonstrated complete occlusion of the aneurysm, and the patient remains asymptomatic. Stent-assisted coil embolization of this iatrogenic pseudoaneurysm was successful in achieving complete, angiographically confirmed aneurysm obliteration, with preservation of the ICA and short-term prevention of hemorrhage or carotidcavernous fistula. The endovascular method provided an effective, relatively low-risk treatment for this difficult lesion, and was an excellent alternative to direct surgical repair. Nonetheless, long-term follow-up review is required before definitive treatment recommendations can be made.