MCL-1 gains occur with high frequency in lung adenocarcinoma and can be targeted therapeutically.

Munkhbaatar, Enkhtsetseg; Dietzen, Michelle; Agrawal, Deepti; Anton, Martina; Jesinghaus, Moritz; Boxberg, Melanie; Pfarr, Nicole; Bidola, Pidassa; Uhrig, Sebastian; Höckendorf, Ulrike; Meinhardt, Anna-Lena; Wahida, Adam; Heid, Irina; Braren, Rickmer; Mishra, Ritu; Warth, Arne; Muley, Thomas; Poh, Patrina S P; Wang, Xin; Fröhling, Stefan; Steiger, Katja; Slotta-Huspenina, Julia; van Griensven, Martijn; Pfeiffer, Franz; Lange, Sebastian; Rad, Roland; Spella, Magda; Stathopoulos, Georgios T; Ruland, Jürgen; Bassermann, Florian; Weichert, Wilko; Strasser, Andreas; Branca, Caterina; Heikenwalder, Mathias; Swanton, Charles; McGranahan, Nicholas; Jost, Philipp J     «

Munkhbaatar, Enkhtsetseg; Dietzen, Michelle; Agrawal, Deepti; Anton, Martina; Jesinghaus, Moritz; Boxberg, Melanie; Pfarr, Nicole; Bidola, Pidassa; Uhrig, Sebastian; Höckendorf, Ulrike; Meinhardt, Anna-Lena; Wahida, Adam; Heid, Irina; Braren, Rickmer; Mishra, Ritu; Warth, Arne; Muley, Thomas; Poh, Patrina S P; Wang, Xin; Fröhling, Stefan; Steiger, Katja; Slotta-Huspenina, Julia; van Griensven, Martijn; Pfeiffer, Franz; Lange, Sebastian; Rad, Roland; Spella, Magda; Stathopoulos, Georgios T; Rulan...     »

Evasion of programmed cell death represents a critical form of oncogene addiction in cancer cells. Understanding the molecular mechanisms underpinning cancer cell survival despite the oncogenic stress could provide a molecular basis for potential therapeutic interventions. Here we explore the role of pro-survival genes in cancer cell integrity during clonal evolution in non-small cell lung cancer (NSCLC). We identify gains of MCL-1 at high frequency in multiple independent NSCLC cohorts, occurring both clonally and subclonally. Clonal loss of functional TP53 is significantly associated with subclonal gains of MCL-1. In mice, tumour progression is delayed upon pharmacologic or genetic inhibition of MCL-1. These findings reveal that MCL-1 gains occur with high frequency in lung adenocarcinoma and can be targeted therapeutically.      «

Evasion of programmed cell death represents a critical form of oncogene addiction in cancer cells. Understanding the molecular mechanisms underpinning cancer cell survival despite the oncogenic stress could provide a molecular basis for potential therapeutic interventions. Here we explore the role of pro-survival genes in cancer cell integrity during clonal evolution in non-small cell lung cancer (NSCLC). We identify gains of MCL-1 at high frequency in multiple independent NSCLC cohorts, occurri...     »