biostudies-literatureVyas ABLRD VANIDCR NIH HHSOffice of Extramural Research, National Institutes of HealthNCI NIH HHSU.S. Department of Veterans AffairsNIH HHSNIGMS NIH HHSe2100670119https://www.ebi.ac.uk/biostudies/studies/S-EPMC8944912biostudies-literatureUnknown119(12)Squamous cell carcinoma of the head and neck (SCCHN) is a devastating disease that continues to have low cure rates despite the recent advances in therapies. Cisplatin is the most used chemotherapy agent, and treatment failure is largely driven by resistance to this drug. Amplification of chromosomal band 11q13 occurs in ∼30% of SCCHN tumors. This region harbors the ANO1 gene that encodes the TMEM16A ion channel, which is responsible for calcium-activated chloride transport in epithelial tissues. TMEM16A overexpression is associated with cisplatin resistance, and high TMEM16A levels correlate with decreased survival. However, the mechanistic underpinning of this effect remains unknown. Lysosomal biogenesis and exocytosis have been implicated in cancer because of their roles in the clearancProceedings of the National Academy of Sciences of the United States of AmericaLysosomal inhibition sensitizes TMEM16A-expressing cancer cells to chemotherapy.PMC8944912R01 DE027185I01 BX003456P50 CA097190R35 GM119412R01 DE028343S10 OD019973R35GM119412Vyas AVillanueva HRajagopalan PHammond GRVKiselyov KPacheco JDuvvuri UBasu DCruz-Rangel SGomez-Casal RSikora AGfalseLysosomal inhibition sensitizes TMEM16A-expressing cancer cells to chemotherapy.Squamous cell carcinoma of the head and neck (SCCHN) is a devastating disease that continues to have low cure rates despite the recent advances in therapies. Cisplatin is the most used chemotherapy agent, and treatment failure is largely driven by resistance to this drug. Amplification of chromosomal band 11q13 occurs in ∼30% of SCCHN tumors. This region harbors the ANO1 gene that encodes the TMEM16A ion channel, which is responsible for calcium-activated chloride transport in epithelial tissues. TMEM16A overexpression is associated with cisplatin resistance, and high TMEM16A levels correlate with decreased survival. However, the mechanistic underpinning of this effect remains unknown. Lysosomal biogenesis and exocytosis have been implicated in cancer because of their roles in the clearanc2022-01-01T00:00:00Z2022 Mar2026-06-18T05:44:26.306Z2025-04-04T20:50:52.815ZS-EPMC89449123528620010.1073/pnas.2100670119