targeted protein degradation<\/a>, or TPD, but there are some newer modalities like RIPTAC that work through different mechanisms.<\/p>\nAt Novartis, we are working across several induced-proximity strategies. The goal is to find the best \u201cevent\u2011based\u201d mechanism to go after key cancer\u2011driving proteins in diseases such as prostate, breast, lung, and gastrointestinal cancers.<\/p>\n
\u00a0<\/p>\n
What\u2019s RIPTAC?<\/p>\n
The acronym itself stands for \u201cRegulated Induced Proximity Targeting Chimeras.\u201d It\u2019s an induced proximity approach that uses what could be described as a \u201ccatch-and-kill\u201d-based mechanism. It involves a molecule that anchors onto a tumor-specific protein while also capturing a separate protein within the same cancer cell\u2014one that\u2019s essential for cell survival. This approach has the potential to effectively kill cancer cells, but since these molecules are specifically targeting cancer-driving proteins, they would spare normal, healthy cells. It has the potential to be transformational across a variety of cancer indications.<\/p>\n
Which cancers does your team focus on?<\/p>\n
We take a disease-focused approach in terms of which cancer types we pursue. Our core areas include prostate cancer and breast cancer. We may have successful, approved medicines in these spaces, but then we look to go further. We ask how we can build on our learnings to create the next generation of medicines to address unmet needs that still remain for patients. For instance, there are many subtypes of breast cancer\u2014can we develop a new therapy so that patients have the right medicine for their specific cancer subtype?<\/p>\n
We’re also invested in gastrointestinal (GI) cancers, including both colorectal cancer and pancreatic cancer. There haven’t been many transformational medicines for these diseases, which is why we think this is an important and innovative space for us to be involved in.<\/p>\n
How has oncology drug discovery changed during your career?<\/p>\n
One thing that\u2019s changed is that, as more and more medicines make it to the clinic, the clinical learnings feed back into drug discovery and we’re able to iterate on that process. What that means is that we learn from patients. We get to understand what needs aren’t being met in these patient populations, whether it’s a cancer subtype that’s not seeing the response you’d expect, or pain points in the patients’ experience as they undergo treatment.<\/p>\n
So we’re not necessarily starting from the ground up\u2014finding a good protein or gene first and then designing a treatment for the target. Instead, we identify an unmet medical need from the clinic, understand the underlying mechanisms and vulnerabilities of the specific cancer, and then we proceed to identify the best protein or gene to target so that we can develop an impactful therapy.<\/p>\n
One thing that\u2019s changed is that, as more and more medicines make it to the clinic, the clinical learnings feed back into drug discovery and we’re able to iterate on that process.<\/p>\n
What are the big challenges right now?<\/p>\n
Many of the well-known targets like HER2, BRAF, and EGFR have been pretty thoroughly targeted. I think the whole industry is waiting for the next wave of breakthroughs, and to see whether that’s going to be on the drug-engineering side or the target side. I have to lean towards the engineering side because I feel like we know the targets, we just can’t hit them the way we want to.<\/p>\n
Take \u03b2-catenin, for instance. It plays a critical role in GI cancer tumorigenesis, but it\u2019s very difficult to drug and, even if you\u2019re able to, it’s not very cancer-specific. There\u2019s normal tissue that also requires \u03b2-catenin signaling, which makes it complicated to target.<\/p>\n
MYC is like that too. It\u2019s been talked about for 40 years as a key cancer dependency but we still haven’t figured out the best way to capitalize on the large amplification of MYC in key cancer indications.<\/p>\n
The field hasn\u2019t yet figured out a way to leverage what we know about some of these seemingly \u201cundruggable\u201d targets. I believe that induced proximity has the potential to help address some of these challenges to drive effective therapies for patients.<\/p>\n
What\u2019s an area in your field that you\u2019d like to explore?<\/p>\n
Tumor suppressors. We talk a lot about oncogenes, but P53 is the most commonly mutated gene in all of cancer and it’s a tumor suppressor. There are some interesting theories out there for correcting P53 mutations to activate it again in these cancers.<\/p>\n
So I think reactivating tumor suppressors could be a promising direction. I don’t know the best way to do it yet, but I think there are some real possibilities out there for innovation.<\/p>\n
What do you hope to see in the future?<\/p>\n
I\u2019d like to see a transformational breakthrough in pancreatic cancer or one of these other harsh GI cancer diagnoses. We’re seeing a rise in colorectal cancer cases across the board and pancreatic cancer is just a devastating disease. If we could see an approval for a targeted therapy that has the potential to be curative, that would mean the world to me.<\/p>\n","protected":false},"excerpt":{"rendered":"At Novartis Biomedical Research, oncology teams around the world are taking on some of the biggest challenges in…\n","protected":false},"author":2,"featured_media":30703,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[127],"tags":[3819,2112,3404,1926,18500,206,265,208,18499,18498],"class_list":{"0":"post-30702","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-novartis","8":"tag-biomedical-research","9":"tag-cancer","10":"tag-chemistry","11":"tag-drug-discovery","12":"tag-induced-proximity","13":"tag-novartis","14":"tag-oncology","15":"tag-san-diego","16":"tag-targeted-protein-degradation","17":"tag-tpd"},"share_on_mastodon":{"url":"https:\/\/pubeurope.com\/@ch\/116216337863357796","error":""},"_links":{"self":[{"href":"https:\/\/www.europesays.com\/ch\/wp-json\/wp\/v2\/posts\/30702","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.europesays.com\/ch\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.europesays.com\/ch\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ch\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ch\/wp-json\/wp\/v2\/comments?post=30702"}],"version-history":[{"count":0,"href":"https:\/\/www.europesays.com\/ch\/wp-json\/wp\/v2\/posts\/30702\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ch\/wp-json\/wp\/v2\/media\/30703"}],"wp:attachment":[{"href":"https:\/\/www.europesays.com\/ch\/wp-json\/wp\/v2\/media?parent=30702"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.europesays.com\/ch\/wp-json\/wp\/v2\/categories?post=30702"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.europesays.com\/ch\/wp-json\/wp\/v2\/tags?post=30702"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}