The surprise retirement of Sen. Bob Corker (R-Tenn.) may signal a rush to the exit door for other longtime Establishment Republicans in the Senate.

Several GOP members of the upper chamber, most of them advanced in age, have struggled to acclimate to the style and agenda of President Donald Trump.

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And some have drifted from their party’s base — a base increasingly willing to back insurgent challenges against incumbents. The prospect of serious electoral mortality appeared to play a role in Corker’s decision. A recent poll found the Tennessee senator trailing potential insurgent GOP challenger Joe Carr.

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And earlier this week, Roy Moore in Alabama actually did knock off an incumbent. Moore, a former state Supreme Court judge, defeated Sen. Luther Strange (R-Ala.) in Tuesday’s special election. Strange had been appointed by a governor tainted with scandal and then vigorously defended by Senate Majority Leader Mitch McConnell (R-Ky.).

Other factors including health concerns and gubernatorial aspirations also could drive the next GOP exits from the Senate. The possible retirees are among the most influential in the chamber: Including Corker, there are four committee chairmen and a member of GOP leadership.

Here are the six of the most likely to consider retirement before the 2018 and 2020 elections.

Orrin Hatch
Sen. Orrin Hatch (R-Utah) is the most likely Republican to next announce retirement.

An octogenarian at 83, Hatch is the longest-serving Republican senator and has the role of the Senate pro tempore, fourth in line for the presidency.

Elected in 1976, Hatch has already admitted he is thinking of retirement, but denied it earlier this year. That has not stopped him from encouraging Republican Mitt Romney from standing by to run in Utah, just in case. Hatch has been a reliable conservative but has not been out in front as a movement leader in a long time.

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Susan Collins
Sen. Susan Collins (R-Maine) is the most liberal Republican in the Senate, with a 2016 rating from the American Conservative Union of only 23 out of a possible 100.

A member of the Senate since 1997, Collins recently made a name for herself anew when she helped kill two different versions of Obamacare repeal.

Collins is up for re-election in 2020, but she has not denied rumors of running for governor in 2018 and is considered by many observers to be seriously considering a bid for the state’s top job.

Jeff Flake
Sen. Jeff Flake (R-Ariz.) is up for his first re-election in 2018 and is possibly the most endangered GOP incumbent in 2018.

Flake, first elected to the House of Representatives in 2000, has all but dared conservatives and Trump loyalists to pull him from office with his frequent criticisms of the president and his agenda. Trump is popular in Arizona with Republicans, and Flake was one of the Senate’s original Never-Trumpers.

Flake, elected to the Senate in 2012, is currently trailing his Republican primary opponent, former State Sen. Kelli Ward, by 25 points, according to an August survey conducted by JMC Analytics and Polling. His approval ratings are also anemic, with 37 percent of Arizona voters approving of Flake’s job, and 45 percent disapproving, according to an August poll by Morning Consult.

Flake isn’t likely to bow out of his re-election bid but does appear in danger of suffering a humiliating primary defeat.

John McCain
Sen. John McCain (R-Ariz.) is facing an extremely serious health challenge after being diagnosed earlier in the year with brain cancer. The chairman of the powerful Armed Services Committee, McCain has long been a persistent thorn in the side of Republican efforts. In recent months the maverick senator has helped torpedo several GOP attempts to partially repeal and replace Obamacare.

McCain has not set a timetable on any decision to step down, but health concerns are likely to force his hand sometime in the next two years.

Lamar Alexander
Sen. Lamar Alexander (R-Tenn.) could follow his fellow Tennessean Corker out the door in 2020 when he is next up for re-election.

Alexander, 77, has been in his Senate office since 2003, but first won the Tennessee governor’s office in 1978. He served until 1986, and later served as secretary of education.

An exit by the Tennesseean senator would open up a powerful chairmanship. Alexander currently chairs the influential Health Care, Education, Labor and Pensions (HELP) Committee.

Mitch McConnell
Senate Majority Leader Mitch McConnell (R-Ky.) was first elected in 1984, pulling off a stunning upset of a Democrat after portraying him as out of touch. In 2017, after failure to repeal Obamacare, McConnell is one of the most unpopular politicians in Congress.

Moore’s victory over Strange in Alabama was particularly embarrassing for McConnell. who backed the incumbent with significant resources from his Senate Majority PAC.

His popularity with Republicans has also eroded, and the president reportedly thinks McConnell, 75, is past his prime, even labeling him “low-energy.”

As frustration continues to mount with the Senate GOP’s lack of legislative progress on key Republican agenda items and as more moderate members of his caucus depart, McConnell might be forced to contemplate an end to his long congressional career.

McConnell is up for re-election in 2020.

(photo credit, homepage image: Gage Skidmore/Chris Eichler, Flickr; photo credit, article image: Gage Skidmore/Jay Inslee/nrcgov, Flickr)