Globally,cervical cancer(CxCa)ranks 4th common cancer among females and led to 569,847 incidences and 311,365 deaths in 2018.80%of CxCa cases occur due to persistent infection with a high-risk subtype of human papillo...Globally,cervical cancer(CxCa)ranks 4th common cancer among females and led to 569,847 incidences and 311,365 deaths in 2018.80%of CxCa cases occur due to persistent infection with a high-risk subtype of human papillomavirus(HPV-16 and 18).Smoking,high par-ity,and co-infection with type 2 herpes simplex or HIV are other known risk factors for CxCa.Major histological subtypes are squamous(70%)and adenocarcinoma(25%).Presently,concur-rent radiation plus cisplatin(CDDP)-based chemotherapy is the standard treatment for CxCa patients.However,CDDP resistance and toxic side effects limit its efficacy,leading to a poorer response rate and an expected overall survival ranging from 10 to 17.5 months.Reduced drug uptake,increased DNA damage repair,increased CDDP inactivation,and overexpressed Bcl-2 or caspase inhibition,are primarily accountable mechanisms for CDDP resistance and improving CDDP’s efficacy remains the major challenge.Poly(ADP-ribosyl)polymerase-1,an effective mediator of nucleotide excision repair pathway,is involved in DNA repair as well as maintaining genomic stability and is significantly expressed in malignant lymphomas,hepa-tocellular-,cervical-and colorectal carcinoma,which has been approved effective in mainte-nance therapy and may serve as an effective target to enhance CDDP sensitivity in CxCa.Here,we summarize the etiology and epidemiology of and treatment for CxCa,the mechanism responsible for chemotherapy resistance,PARP inhibitor as a possible therapy for CxCa,and other possible chemotherapeutic options for CxCa treatment.展开更多
文摘Globally,cervical cancer(CxCa)ranks 4th common cancer among females and led to 569,847 incidences and 311,365 deaths in 2018.80%of CxCa cases occur due to persistent infection with a high-risk subtype of human papillomavirus(HPV-16 and 18).Smoking,high par-ity,and co-infection with type 2 herpes simplex or HIV are other known risk factors for CxCa.Major histological subtypes are squamous(70%)and adenocarcinoma(25%).Presently,concur-rent radiation plus cisplatin(CDDP)-based chemotherapy is the standard treatment for CxCa patients.However,CDDP resistance and toxic side effects limit its efficacy,leading to a poorer response rate and an expected overall survival ranging from 10 to 17.5 months.Reduced drug uptake,increased DNA damage repair,increased CDDP inactivation,and overexpressed Bcl-2 or caspase inhibition,are primarily accountable mechanisms for CDDP resistance and improving CDDP’s efficacy remains the major challenge.Poly(ADP-ribosyl)polymerase-1,an effective mediator of nucleotide excision repair pathway,is involved in DNA repair as well as maintaining genomic stability and is significantly expressed in malignant lymphomas,hepa-tocellular-,cervical-and colorectal carcinoma,which has been approved effective in mainte-nance therapy and may serve as an effective target to enhance CDDP sensitivity in CxCa.Here,we summarize the etiology and epidemiology of and treatment for CxCa,the mechanism responsible for chemotherapy resistance,PARP inhibitor as a possible therapy for CxCa,and other possible chemotherapeutic options for CxCa treatment.
