PIK3CD and mantle cell lymphoma: However, only a portion of relapsed/refractory MCL patients respond to the rapamycin analogues and the response is generally not durable.[28-32] It has been reported that several signaling feedback loops might attenuate the effectiveness of these compounds,[17] so dual catalytic inhibition of PI3K/mTOR could be a good strategy to address PI3K/Akt/mTOR resistance mechanisms.