The ladder-leading Penrith Panthers extended their winning streak to six games with a resilient 22-14 victory over Gold Coast Titans on Sunday.

Three tries in the opening 30 minutes and a second-half sealer from Malakai Watene-Zelezniak secured another valuable result for the undermanned and inexperienced Panthers, who were without four players from the team that beat North Queensland Cowboys last weekend.

Ivan Cleary's side have now notched nine wins, a draw and a solitary defeat after 11 rounds, the club's best ever record at this stage of an NRL season.

Josh Mansour and teenager Stephen Crichton both went over inside the opening 15 minutes to set up the victory, which restores Penrith's one-point lead over Melbourne Storm and Parramatta Eels.

The impressive Isaah Yeo added his side's third following Jamal Fogarty's long-range try before the Titans hit back forcefully through Brian Kelly and Anthony Don.

That burst cut the difference to two points at half-time but Watene-Zelezniak's effort in the 60th minute and Nathan Cleary's three conversions helped the Panthers withstand the challenge.

Newcastle Knights endured a miserable 80 minutes in the early match, losing Andrew McCullough and Connor Watson to season-ending injuries en route to a shock 18-12 loss to Canterbury Bulldogs at a wet McDonald Jones Stadium.

McCullough and Watson were forced from the field with serious hamstring and Achilles injuries respectively within the first 30 minutes and Knights coach Adam O'Brien later declared neither would return in 2020.

The bottom-placed Bulldogs took full advantage of their wounded opponents, with Raymond Faitala-Mariner and Jake Averillo adding second-half tries to Aiden Tolman's 11th-minute opener.

Hymel Hunt and Sione Mata'utia eventually brought the Knights back into the contest, but the fightback came too late to deny the visitors their second win of the season.