FILE - In this Sunday Feb. 15, 2015 file photo and provided on by the Syrian anti-government activist group Aleppo Media Center (AMC), which has been authenticated based on its contents and other AP reporting, shows Syrian rebels firing locally made shells against the Syrian government forces, in Aleppo, Syria. Islamic State militants entered a Syrian opposition stronghold in the country's north on Saturday, clashing with rebels on the edges of the town as the extremist group built on its most significant advance near the Turkish border in two years, Syrian opposition groups and IS media said. (AP Photo/Aleppo Media Center, AMC, File)Uncredited
FILE - In this Sunday Feb. 15, 2015 file photo and provided on by the Syrian anti-government activist group Aleppo Media Center (AMC), which has been authenticated based on its contents and other AP reporting, shows Syrian rebels firing locally made shells against the Syrian government forces, in Aleppo, Syria. Islamic State militants entered a Syrian opposition stronghold in the country's north on Saturday, clashing with rebels on the edges of the town as the extremist group built on its most significant advance near the Turkish border in two years, Syrian opposition groups and IS media said. (AP Photo/Aleppo Media Center, AMC, File)Uncredited

Islamic State militants entered a major Syrian opposition stronghold in the country’s north on Saturday, clashing with rebels on the edges of the town as the extremist group builds on its most significant advance near the Turkish border in two years — even as it loses ground elsewhere in the country and in neighboring Iraq.

The town of Marea, just north of Aleppo city, has long been considered a bastion of relatively moderate Syrian revolutionary forces fighting to topple Assad. The Islamic State assault underlined the weakness of the groups fighting under the loose banner of the so-called Free Syrian Army that have been struggling to survive.

More than 160,000 civilians have been trapped by the fighting, which also forced the evacuation of one of the few remaining hospitals in the area.

On Saturday, Islamic State fighters staged two suicide bombings targeting “opposition forces” near Marea, Islamic State said via its news agency, Aamaq.

Following the suicide bombings, militants entered Marea and fighting began inside the town, according to the Syrian Observatory for Human Rights, a Britain-based opposition media outfit that tracks Syria’s civil war.

Dr. Abdel Rahman Alhafez, who heads one of the last remaining hospitals in Marea, said the town was encircled and his hospital under threat since Friday. “We need urgent protection for the hospital or a way out,” he said in an emailed statement.

The Islamic State offensive targeting Syrian opposition strongholds near the Turkish border began on Thursday night.

On Friday, militants of the group captured six villages near Azaz, triggering intense fighting that trapped tens of thousands of civilians unable to flee to safety while Turkey’s border remains closed. A few hundred fled west to the Kurdish-held enclave of Afrin.

People are “terrified for their lives,” the International Rescue Committee said in a statement. The group said it has received confirmed reports that at least four entire families, including women and children, were killed Friday on the outskirts of Azaz.

The U.N. refugee agency said it was “deeply concerned” about the fighting affecting thousands of vulnerable civilians.