We have discovered that resistance to Lapatinib in colon cancer cells is mediated by increased expression of mitochondrial and endoplasmic reticulum protective MCL 1 and BCL XL proteins with reduced expression of professional apoptotic BAX and mutation of p53. The BCL 2 family of proteins regulates the intrinsic mitochondrial apoptosis pathway. Defensive BCL 2 family proteins associate via BH3 areas with professional apoptotic family members including BAK and BAX. BAK and BAX, when produced from protective BCL BMN 673 2 proteins, could perturb the mitochondrial membrane forming pores that permit release of cytochrome c and AIF, leading ultimately to apoptosis. Tumefaction cells utilize a number of things to keep up viability, including loss of death receptor expression, by losing expression of professional apoptotic BH3 website proteins, BAX or by increasing expression of anti apoptotic BCL 2 family members, MCL 1. In the case of protective BCL 2 family proteins, several clinically relevant small molecule inhibitors have now been developed that specifically bind to the BCL 2 family protein, without changing appearance of the protein and that block the binding of professional apoptotic BH3 domain proteins. The drug induced dissociation of BCL Eumycetoma 2 protein from dangerous BH3 domain protein in higher quantities of free BH3 domain protein which will facilitate mitochondrial dysfunction and encourage the toxicity of other therapeutic agents. The current studies decided whether inhibition of BCL 2 family function using both CDK inhibitors to reduce protein expression or using Obatoclax to restrict BH3 site function, can promote tumefaction cell death. The impact of combined exposure of breast cancer cells to the ERBB1/ERBB2 inhibitor lapatinib and the CDK inhibitor flavopiridol was first investigated. In short term cell viability assays simultaneous combined coverage of breast cancer cells to flavopiridol and lapatinib resulted in a larger than additive induction of short term cell killing compared to either drug individually, which was synergistic as dependant on Median Dose Effect studies with Combination Index values consistently less than 1. These findings correlated with dephosphorylation of AKT, ERK1/2 and ERBB1. Similar studies with still another CDK chemical, roscovitine, generated information BAY 11-7821 that was very similar to that generated using flavopiridol. Constitutive activation of MEK1 and of MEK1 and AKT, protected breast cancer cells from flavopiridol lapatinib lethality that correlated with additional MCL 1 expression. Overexpression of either BCL XL or of dominating negative caspase 9, although not c FLIP s, suppressed drug lethality. Lapatinib improved the price of flavopiridol caused MCL 1 destruction and overexpression of MCL 1 guarded cells from flavopiridol lapatinib lethality. Treatment of cells with flavopiridol and lapatinib increased BAK and BAX initial and knock down of BAX BAK suppressed flavopiridol lapatinib lethality. In a cancerous colon cells that were generated to be lapatinib resilient and that we’d demonstrated was as a result of elevated basal levels of MCL 1, flavopiridol partially circumvented lapatinib resistance.