Abstract: Provided herein are compounds and compositions thereof that may be capable of disrupting, interrupting, and/or preventing an interaction between a small GTPase protein and a PI3K protein (e.g., PI3Ka). The present disclosure also provides methods of treating cancers and other indications with such compounds or compositions thereof.

Abstract: The present disclosure provides a method of treating cancer in a subject. The method including administering to the subject: a) a therapeutically effective amount of a PTPN11 inhibitor; and b) a therapeutically effective amount of an EGFR inhibitor, wherein the PTPN11 inhibitor is represent by formula (I): (I) or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, conformational isomer, tautomer, or a combination thereof, wherein the subscripts a and b, Y1, Y2, and R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, and R13 are as provided herein. In particular, the present disclosure provides a method of treating a solid tumor (e.g., an advanced non-small cell lung cancer) with a therapeutically effective amount of a compound of formula (10b) (i.e., 6-((3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl)-3-(Ra)-(2,3-dichlorophenyl)-2,5-dimethylpyrimidin-4(3H)-one) in combination with an EGFR inhibitor such as osimertinib.

Abstract: The present disclosure provides a method of treating cancer in a subject. The method including administering to the subject: a) a therapeutically effective amount of a compound of formula (I); and b) a therapeutically effective amount of sotorasib, wherein the compound of formula (I) is represented by (I), or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, conformational isomer, tautomer, or a combination thereof. In particular, the present disclosure provides a method of treating a solid tumor (e.g., an advanced or metastatic non-small cell lung cancer) with a therapeutically effective amount of a compound of formula (10b) (i.e., 6-((3S,4S)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl)-3-(Ra)-(2,3-dichlorophenyl)-2,5-dimethylpyrimidin-4(3H)-one) in combination with sotorasib in a subject, wherein the subject has one or more mutations in KRAS, such as KRAS G12C.

Abstract: The invention is directed to a console coupleable to an indwelling catheter for monitoring interstitial pressure, collecting and withdrawing excess interstitial fluid and infusing fluids into the treated area.