Maybe a 442 with James and Mandzukic could work. James doesn't have the defensive ability of cuadrado though
I'd like, and I've been saying it for a long time, is that the formation should possibly evolve to a 4-3-2-1 if we get the right players like Tolisso and James. This way we can easily either play two supporting strikers or attacking midfielders behind Higuain or Mandzukic, or switch to a wider 4-3-3 with wingers in the midst of a game. James, Dybala, Cuadrado, Pjaca and to some extent Mandzu (also to some extent Kean, Clemenza and Orsolini from our youth) are very versatile players, that can either play out wide or cut inside with ease. If we take off one of our attackers for a physical B2B like Tolisso, we lessen the need of our wingers needing to push back as much.
A)-----------------------------B)-----------------------------------
Tolisso-Marchisio-Pjanic ----Khedira--NewMF--Sturaro----
---Dybala------James---- ---Cuadrado--------------Pjaca---
----------Higuain--------- --------------Mandzukic-----------
Lots of freedom for the supporting strikers, and if they're creative they can switch sides, overlap, go wide and switch position with the striker to confuse defenses. Think Higuains goal tally would increase aswell; two talented supporting players feeding him is how he scored crazy amounts of goals at Napoli too.